WorldWideScience

Sample records for thalidomide dexamethasone induction

  1. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

    Science.gov (United States)

    Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

    2012-01-01

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior

  2. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study.

    Science.gov (United States)

    Rosiñol, Laura; Oriol, Albert; Teruel, Ana Isabel; Hernández, Dolores; López-Jiménez, Javier; de la Rubia, Javier; Granell, Miquel; Besalduch, Joan; Palomera, Luis; González, Yolanda; Etxebeste, María Asunción; Díaz-Mediavilla, Joaquín; Hernández, Miguel T; de Arriba, Felipe; Gutiérrez, Norma C; Martín-Ramos, María Luisa; Cibeira, María Teresa; Mateos, María Victoria; Martínez, Joaquín; Alegre, Adrián; Lahuerta, Juan José; San Miguel, Jesús; Bladé, Joan

    2012-08-23

    The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/VBAD/B (35% vs 21%, P = .01). The median progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P = .01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/VBAD/B (46% vs 38%, P = .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).

  3. Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma.

    NARCIS (Netherlands)

    Lokhorst, H.M.; Schmidt-Wolf, I.; Sonneveld, P.; Holt, B. van der; Martin, H.; Barge, R.; Bertsch, U.; Schlenzka, J.; Bos, G.M.; Croockewit, S.; Zweegman, S.; Breitkreutz, I.; Joosten, P.; Scheid, C.; Marwijk-Kooy, M. van; Salwender, H.J.; Oers, M.H. van; Schaafsma, R.; Naumann, R.; Sinnige, H.A.M.; Blau, I.; Delforge, M.; Weerdt, O. de; Wijermans, P.W.; Wittebol, S.; Duersen, U.; Vellenga, E.; Goldschmidt, H.

    2008-01-01

    In the prospective phase 3 HOVON-50/GMMG-HD3 trial, patients randomized to TAD (thalidomide, doxorubicin, dexamethasone) had a significantly higher response rate (at least PR) after induction compared with patients randomized to VAD (vincristine, adriamycin, dexamethasone, 72% vs. 54%, p<0.001).

  4. Elotuzumab in combination with thalidomide and low-dose dexamethasone

    DEFF Research Database (Denmark)

    Mateos, Maria-Victoria; Granell, Miguel; Oriol, Albert

    2016-01-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-...

  5. Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma.

    Science.gov (United States)

    Mark, Tomer M; Bowman, Isaac A; Rossi, Adriana C; Shah, Manan; Rodriguez, Melissa; Quinn, Ryann; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Jayabalan, David; Ely, Scott; Coleman, Morton; Chen-Kiang, Selina; Niesvizky, Ruben

    2014-12-01

    We studied T-BiRD (thalidomide [Thalomid(®)], clarithromycin [Biaxin(®)], lenalidomide [Revlimid(®)] and dexamethasone) in symptomatic, newly diagnosed multiple myeloma. In 28-day cycles, patients received dexamethasone 40 mg/day on days 1, 8, 15, 22, clarithromycin 500 mg twice daily on days 1-28; lenalidomide 25 mg/day on days 1-21; and thalidomide 100 mg/day (50 mg/day on days 1-7 of cycle 1 only) on days 1-28. Twenty-six patients received a median of 6 cycles (range 0-41). Overall response rate (ORR) was 80% for the group and 100% in 11 patients who underwent autologous stem cell transplantation as part of first-line therapy. The 4-year overall survival rate was 74.9%, and the median progression-free survival was 35.6 months. Eight patients discontinued due to regimen toxicity. Grade 3 non hematologic toxicity affected 12 patients (46.2%). T-BiRD is a highly active regimen with potential toxicity limitations. ClinicalTrials.gov identifier: NCT00538733.

  6. Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Shenghao Wu

    2015-01-01

    Full Text Available Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM patients with the therapy of subcutaneous (subQ administration of bortezomib and dexamethasone plus thalidomide (VTD regimen. Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group.The efficacy and safety of two groups were analyzed retrospectively. Results. The overall remission (OR after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05. No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P=0.848 and progression-free survival (median 22 months versus 25 months; P=0.725 between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50% than VTD group (80%, P=0.015. Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

  7. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation

    Science.gov (United States)

    Davies, Faith E.; Gregory, Walter M.; Russell, Nigel H.; Bell, Sue E.; Szubert, Alexander J.; Coy, Nuria Navarro; Cook, Gordon; Feyler, Sylvia; Byrne, Jenny L.; Roddie, Huw; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Jackson, Graham H.; Child, J. Anthony

    2011-01-01

    As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111. PMID:21652683

  8. Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Mateos, María-Victoria; Granell, Miguel; Oriol, Albert; Martinez-Lopez, Joaquin; Blade, Joan; Hernandez, Miguel T; Martín, Jesus; Gironella, Mercedes; Lynch, Mark; Bleickardt, Eric; Paliwal, Prashni; Singhal, Anil; San-Miguel, Jesus

    2016-11-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM. © 2016 John Wiley & Sons Ltd.

  9. LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.

    Science.gov (United States)

    Shu, Chang; Zeng, Tianmei; Gao, Shouhong; Xia, Tianyi; Huang, Lifeng; Zhang, Feng; Chen, Wansheng

    2016-08-15

    Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. The determination of 6 commonly used drug concentrations, including thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin, in MM patients was of great clinical interest. Herein, we reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge(®) BEH C18 column (2.5μm, 2.1 mm×50mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3mL/min. All analytes showed good correlation coefficients (r>0.996), and LLOQ of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin were 4, 2, 2, 2, 2 and 2ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The LC-MS/MS based assay described in this article may improve future clinical studies evaluating common therapeutics for MM treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Updated survivals and prognostic factor analysis in myeloma treated by a staged approach use of bortezomib/thalidomide/dexamethasone in transplant eligible patients

    Directory of Open Access Journals (Sweden)

    Chim Chor

    2010-11-01

    Full Text Available Abstract Background Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM. We have reported a promising complete remission (CR rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT. Methods Herein, with an additional 13 months of follow-up, we reported the updated survivals, and examined potential prognostic factors impacting event-free (EFS and overall survival (OS. Results With a median follow-up of 30 months, the projected OS was 73% and EFS was 50.2%. Age, gender, clinical stage and DAPK methylation could not account for the differential chemosensitivity. Advanced ISS stage and DAPK methylation adversely impacted OS whereas oligoclonal reconstitution predicted superior EFS. Conclusions Our staged approach illustrated an economical use of expensive targeted agents while preserving a good CR rate and OS. The comparable survivals of chemosensitive and less chemosensitive patients suggested the staged approach might have abolished the adverse prognostic impact of suboptimal chemosensitivity. Finally, the adverse impact of DAPK methylation and favorable impact of oligoclonal reconstitution in myeloma warrants further study.

  11. Outcomes of autologous transplantation for multiple myeloma according to different induction regimens

    Directory of Open Access Journals (Sweden)

    Edvan de Queiroz Crusoe

    2014-01-01

    Full Text Available Background: Induction therapy followed by high-dose chemotherapy and autologous transplantation is the standard treatment for suitable patients with multiple myeloma. Objective: The aim of this study was to assess whether induction therapy with thalidomidecontaining regimens was associated with improved results compared to vincristine, doxorubicin, and dexamethasone, and whether cyclophosphamide, thalidomide, and dexamethasone were associated with better results than thalidomide and dexamethasone. Methods: The records of 152 patients who underwent autologous transplantation at this institution from August of 2004 to January of 2012 were reviewed, selecting those with at least partial response to a maximum of eight cycles of induction therapy and sufficient follow-up information for analysis. Results: This study included 89 patients; 44 were female, with a mean age of 55 years (there was a significant trend for increasing age over the years of the study.The median number of induction therapy cycles was four, again with a trend of increase over the years.At least a very good partial response to induction therapy was achieved more often in the cyclophosphamide, thalidomide, and dexamethasone group (61.1% and in the thalidomide and dexamethasone group (59.2% than in the vincristine, doxorubicin, and dexamethasone group (16.2%. The overall median progression-free survival was 34 months, with no statistically significant difference between the three groups. The overall median survival was not reached, and there was no significant difference between the three groups; the estimated five-year overall survival was 55%. Conclusion: Although the quality of responses appeared to be better with thalidomidecontaining regimens, these improvements did not translate into improved long-term outcomes. Given its track record, cyclophosphamide, thalidomide, and dexamethasone is currently considered the preferred regimen for first-line induction therapy in the

  12. Synergistic Effect of Sodium Butyrate and Thalidomide in the Induction of Fetal Hemoglobin Expression in Erythroid Progenitors Derived from Cord Blood CD133 + Cells

    Directory of Open Access Journals (Sweden)

    Ali Dehghanifard

    2012-07-01

    Full Text Available Background: The use of drugs with the ability to induce production of fetal hemoglobin as a novel therapeutic approach in treating β-Hemoglobinopathies is considered. γ-globin gene expression inducer drugs including sodium butyrate and thalidomide can reduce additional α-globin chains accumulation in erythroid precursors. Materials and Methods: In this experimental study, MACS kit was used to isolate CD133+ cells of umbilical cord blood. Further, the effect of two drugs of thalidomide and sodium butyrate were separately and combined studied on the induction of quantitative expression of β-globin and γ-globin genes in erythroid precursor cells derived from CD133+ stem cells in-vitro. For this purpose, the technique SYBR green Real-time PCR was used.Results: Flow cytometry results showed that approximately 95% of purified cells were CD133+. Real-time PCR results also showed the increased levels of γ-globin mRNA in the cell groups treated with thalidomide, sodium butyrate and combination of drugs as 2.6 and 1.2 and 3.5 times respectively, and for β-globin gene, it is respectively 1.4 and 1.3 and 1.6 times compared with the control group (p<0.05.Conclusion: The study results showed that the mentioned drug combination can act as a pharmaceutical composition affecting the induction of fetal hemoglobin expression in erythroid precursor cells derived from CD133 + cells.

  13. Thalidomide neurotoxicity

    DEFF Research Database (Denmark)

    Clemmensen, O J; Olsen, P Z; Andersen, Klaus Ejner

    1984-01-01

    Of six patients treated with thalidomide for either prurigo nodularis or discoid lupus erythematosus, four had paresthesias in the hands and feet and one also complained of muscular pain and stiffness. Clinical neurological findings in all four patients were normal. Subsequent electrophysiological...

  14. Effect of Intravenous Dexamethasone on Preparing the Cervix and Labor Induction

    Directory of Open Access Journals (Sweden)

    Fatemeh Laloha

    2015-10-01

    Full Text Available The use of corticosteroids is one of the methods put forward for the strengthening and speeding up the process of labor. After identification of glucocorticoid receptors in human amnion, the role of corticosteroids in starting the process of labor has been studied in numerous studies. The purpose of this study was to determine the effect of intravenous Dexamethasone on preparing the cervix and on labor induction. A randomized, clinical, and double – blind trial was conducted on 172 women divided into a control and an experimental group. The inclusion criteria were that they had to be primparous, in or before the 40th week of pregnancy, and with Bishop scores (B.S.s of 4 or lower. The exclusion criteria were diabetes, preeclampsia, macrosomia, twin pregnancy, rupture of the membrane (ROM, breech, and women suffering from background diseases. The B.S.s of the women was measured in charge of the study, and each woman was intravenously injected with eight milligrams of Dexamethasone or eight milligrams of distilled water. Four hours after the injections, the B.S.s of the participants was measured, and they were put under the conditions of labor induction using oxytocin. Information was collected in checklists A and B. The patients were compared with respect to B.S., the time the induction started, the average interval between the start of induction and the beginning of the active phase of childbirth, and the average length of time between the start of the active phase and the second stage of childbirth. The first and five minutes Apgar scores of the two groups of women were compared. The frequencies, the means,  and the standard deviations were calculated using the SPSS – 16 software, and analysis of the results was performed with the Student’s t- test and the chi-square test with PPPP

  15. Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

    International Nuclear Information System (INIS)

    Hreiche, Raymond; Megarbane, Bruno; Pirnay, Stephane; Borron, Stephen W.; Monier, Claire; Risede, Patricia; Milan, Nathalie; Descatoire, Veronique; Pessayre, Dominique; Baud, Frederic J.

    2006-01-01

    In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg -1 was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg -1 buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P -1 buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts

  16. Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

    Science.gov (United States)

    Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

    2007-12-01

    Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

  17. Thalidomide and Pregnancy

    Science.gov (United States)

    ... It is recommended that two different and reliable methods of birth control be used if a woman is taking thalidomide. Thalidomide may decrease the effectiveness of oral contraceptives (birth control pills). The manufacturer developed the STEPS ( ...

  18. Thalidomide in dermatology: Revisited

    Directory of Open Access Journals (Sweden)

    Iffat Hassan

    2015-01-01

    Full Text Available The use of thalidomide in relation to dermatology is well- known and enough data is available in the literature about various aspects of thalidomide. Despite being an interesting and useful drug for many dermatoses, it is associated with many health hazards including the birth defects, phocomelia. We hereby present a comprehensive review about thalidomide and its application in dermatology.

  19. Adding Fludarabine to Cyclophophamide-dexamethason induction therapy impair stem cell harvest in MM

    DEFF Research Database (Denmark)

    Johnsen, Hans Erik; Meldgaard Knudsen, Lene; Mylin, Anne Kærsgaard

    BACKGROUND AND OBJECTIVES Recent data have indicated that the myeloma cell hierarchy includes resistant Recent data have indicated that the myeloma cell hierarchy includes resistant circulating clonal memory B cells, which differ considerably from the classical end stage plasma cells infiltrating......, placebo controlled, single blinded, phase II study evaluating This was a randomized, placebo controlled, single blinded, phase II study evaluating toxicity and safety of Fludarabine added to Cyclophosphamide and Dexamethasone (CyDex) as induction therapy in younger patients with untreated and treatment...

  20. Induction of regulatory dendritic cells by dexamethasone and 1alpha,25-Dihydroxyvitamin D(3)

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Gad, Monika; Walter, Mark R

    2004-01-01

    D(3) the active form of Vitamin D(3) (D(3)) in combination with dexamethasone (Dex) has a synergistic effect on LPS-induced maturation of DC. Monocyte-derived DCs cultured with D(3) and Dex during LPS-induced maturation have a low stimulatory effect on allogeneic T cells comparable...

  1. Thalidomide for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy

    Directory of Open Access Journals (Sweden)

    Geng Song

    2017-03-01

    Full Text Available Background Antiemetic guidelines recommend co-administration of agents to maximize the prevention of chemotherapyinduced nausea and vomiting (CINV, however, the control of delayed CINV is still not satisfactory. The purpose of this study was to evaluate the effectiveness and safety of thalidomide in the prevention of CINV. Methods Of 89 patients enrolled, 83 chemotherapy-naïve patients receiving highly emetogenic chemotherapy (cisplatin 70mg/m2 were randomized into two groups: standard therapy group (ondansetron on day 1, metoclopramide and dexamethasone on days one to five and thalidomide group (in addition to standard emesis prevention, patients received oral 100mg thalidomide on days one to five. Patients recorded nausea and vomiting episodes in a diary. The primary end point was the efficacy of thalidomide in controlling vomiting and nausea on days one to five post cisplatin, and the secondary end point was the safety of the thalidomide. Results No significant differences of complete response rates (no emesis, no use of rescue therapy and no nausea were observed between the two groups, while the percentages of patients with complete response of delayed vomiting on day four and day five were higher in the thalidomide group, furthermore, the complete response rate of delayed nausea for thalidomide group and standard therapy group showed significant differences. Thalidomide group showed a similar safety profile as standard emesis prevention group. Conclusion Addition of thalidomide was generally well tolerated and improved prevention of CINV in patients receiving cisplatinbased chemotherapy to some degree, especially for delayed nausea.

  2. Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy.

    Science.gov (United States)

    Talamo, Giampaolo; Angtuaco, Edgardo; Walker, Ronald C; Dong, Li; Miceli, Marisa H; Zangari, Maurizio; Tricot, Guido; Barlogie, Bart; Anaissie, Elias

    2005-08-01

    To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period. With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones. AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

  3. Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

    Directory of Open Access Journals (Sweden)

    Chim Chor

    2012-06-01

    Full Text Available Abstract Background We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone before autologous stem cell transplantation (ASCT. Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone or VTD (bortezomib/thalidomide/dexamethasone induction, and analysed prognostic factors for outcome. Patients and methods Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25, PAD (N = 31, VTD (N = 35]. and received thalidomide maintenance for 2 years post-ASCT. Results 43 (47.3% patients had International Staging System (ISS III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS and event-free (EFS survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. Conclusions These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.

  4. The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

    Directory of Open Access Journals (Sweden)

    Jing Lu

    2015-01-01

    Full Text Available The International Staging System (ISS is the most important prognostic system for multiple myeloma (MM. It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p<0.001, and the median progression-free survival (PFS was 30/29.5/25 months (p=0.072, respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system.

  5. Bcl2-independent chromatin cleavage is a very early event during induction of apoptosis in mouse thymocytes after treatment with either dexamethasone or ionizing radiation.

    Science.gov (United States)

    Hahn, Peter J; Lai, Zhi-Wei; Nevaldine, Barbara; Schiff, Ninel; Fiore, Nancy C; Silverstone, Allen E

    2003-11-01

    We have quantified the emergence of early chromatin breaks during the signal transduction phase of apoptosis in mouse thymocytes after treatment with either ionizing radiation or dexamethasone. Dexamethasone at 1 microM can induce significant levels of DNA breaks (equivalent to the amount induced directly by 7.5 Gy ionizing radiation) within 0.5 h of treatment. The execution phase of apoptosis was not observed until 4-6 h after the same treatment. The presence of the Bcl2 transgene under the control of the p56lck promoter almost completely inhibited apoptosis up to 24 h after treatment, but it had virtually no effect on the early chromatin cleavage occurring in the first 6 h. Ionizing radiation induced chromatin cleavage both directly by damaging DNA and indirectly with kinetics similar to the induction of chromatin cleavage by dexamethasone. The presence of the Bcl2 transgene had no effect on the direct or indirect radiation-induced cleavage in the first 6 h, but after the first 6 h, the Bcl2 gene inhibited further radiation-induced chromatin cleavage. These results suggest that endonucleases are activated within minutes of treatment with either dexamethasone or ionizing radiation as part of the very early signal transduction phase of apoptosis, and prior to the irreversible commitment to cell death.

  6. Thalidomide-associated thrombocytopenia

    NARCIS (Netherlands)

    Duyvendak, M; Naunton, M.; Kingma, B.J; Brouwers, J.R.B.J.

    2005-01-01

    OBJECTIVE: To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY: A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy.

  7. Forgive sins: rise of thalidomide

    Directory of Open Access Journals (Sweden)

    Yugandar Inakanti

    2014-04-01

    Full Text Available Thalidomide was originally used as a Wonder Drug to treat morning sickness and insomnia in pregnant women in late 1950s. It became apparent in early 1960s that thalidomide treatment resulted in severe birth defects in thousands of children. Then it was banned in most of countries. Later on discovered anti-inflammatory and anti-angiogenic properties of Thalidomide proved to be useful for treatment of leprosy and multiple myeloma. A series of immunomodulatory drugs created by chemical modification of thalidomide have been developed to overcome the original devastating side effects. It’s being investigated extensively as a treatment for many other severe cutaneous disorders and advanced cancers. We briefly review pharmacological and the therapeutic profile of thalidomide.

  8. [Thalidomide teratogenicity and its direct target identification].

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Handa, Hiroshi

    2015-01-01

    Half a century ago, thalidomide was developed as a sedative drug and was wildly used over 40 countries. However the drug has serious birth defects such as amelia and phocomelia. Now thalidomide is regarded as a clinically effective drug and used for the treatment of multiple myeloma under strict controls. The direct target of thalidomide had been a long-standing question. We identified cereblon as a primary direct target protein for thalidomide teratogenicity using new affinity bead technology in 2010. In this review, we introduce an overview of thalidomide teratogenicity, a story about how we identified cereblon, and recent advances in cereblon studies.

  9. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.

    Science.gov (United States)

    Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony

    2012-01-05

    Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

  10. Thalidomide increases human keratinocyte migration and proliferation.

    Science.gov (United States)

    Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

    1999-11-01

    Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

  11. Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure.

    Science.gov (United States)

    Theodorakis, Nicholas G; Wang, Yining N; Korshunov, Vyacheslav A; Maluccio, Mary A; Skill, Nicholas J

    2015-04-14

    Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. Wild type, inducible nitric oxide synthase (iNOS)(-/-) and endothelial nitric oxide synthase (eNOS)(-/-) mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS(-/-) PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS(-/-) PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS(-/-) or iNOS(-/-) mice. Thalidomide acutely increased plasma NOx in wild type and eNOS(-/-) mice but not iNOS(-/-) mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, e

  12. Stability of an extemporaneously prepared thalidomide suspension.

    Science.gov (United States)

    Kraft, Shawna; Johnson, Cary E; Tyler, Ryan P

    2012-01-01

    The short-term physical and chemical stability of an oral suspension of thalidomide 20 mg/mL was studied. An oral suspension of thalidomide 20 mg/mL was prepared by emptying the contents of 12 100-mg thalidomide capsules into a glass mortar; 30 mL of Ora-Plus and 30 mL of Ora-Sweet were mixed and added to the thalidomide powder to make a final volume of 60 mL. Three identical samples of the formulation were prepared and placed in 2-oz amber plastic bottles with child-resistant caps and stored under refrigeration (3-5 °C). A 1-mL sample was withdrawn from each of the three samples with a micropipette immediately after preparation and at 7, 14, 21, 28, and 35 days. After further dilution to an expected concentration of 20 μg/mL with acetonitrile-methanol and then dilution with mobile phase, the samples were assayed in duplicate using stability-indicating high-performance liquid chromatography. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point; stability was defined as the retention of at least 90% of the initial concentration of thalidomide. At least 92% of the initial thalidomide concentration remained throughout the 35-day study period. There were no detectable changes in color, odor, or pH and no visible microbial growth in any sample. An extemporaneously prepared suspension of thalidomide 20 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet was stable for at least 35 days when stored in 2-oz amber plastic bottles under refrigeration.

  13. Antitumorigenic Evaluation of Thalidomide Alone and in Combination with Cisplatin in DBA2/J Mice

    Directory of Open Access Journals (Sweden)

    Jean Marie B. Ruddy

    2002-01-01

    thalidomide failed to inhibit cell proliferation. However, cisplatin treatment with or without thalidomide, significantly inhibited the multiplication of both cell lines in a dose dependent manner. Thalidomide does not appear to be a beneficial adjuvant to cisplatin treatment.

  14. Induction regimens for transplant-eligible patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Zeng ZH

    2017-07-01

    Full Text Available Zi-Hang Zeng,1,2 Jia-Feng Chen,1,2 Yi-Xuan Li,1,2 Ran Zhang,1,2 Ling-Fei Xiao,1,2 Xiang-Yu Meng1,2 1Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, 2Department of Evidence-Based Medicine and Clinical Epidemiology, Second Clinical College of Wuhan University, Wuhan, People’s Republic of China Objective: The aim of this study was to compare the early efficacy and survivals of induction regimens for transplant-eligible patients with untreated multiple myeloma. Materials and methods: A comprehensive literature search in electronic databases was conducted for relevant randomized controlled trials (RCTs. Eligible studies were selected according to the predefined selection criteria, before they were evaluated for methodological quality. Basic characteristics and data for network meta-analysis (NMA were extracted from included trials and pooled in our meta-analysis. The end points were the overall response rate (ORR, progression-free survival (PFS, and overall survival (OS. Results: A total of 14 RCTs that included 4,763 patients were analyzed. The post-induction ORR was higher with bortezomib plus thalidomide plus dexamethasone (VTD regimens, and VTD was better than the majority of other regimens. For OS, VTD plus cyclophosphamide (VTDC regimens showed potential superiority over other regimens, but the difference was not statistically significant. The PFS was longer with thalidomide plus doxorubicin plus dexamethasone (TAD regimens for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM. Conclusion: The NMA demonstrated that the VTD, VTDC, and TAD regimens are most beneficial in terms of ORR, OS, and PFS for transplant-eligible patients with NDMM, respectively. Keywords: multiple myeloma, newly diagnosed, transplant-eligible, induction therapies, network meta-analysis

  15. Identification of a primary target of thalidomide teratogenicity.

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Suzuki, Takayuki; Ogura, Toshihiko; Hotta, Kentaro; Imamura, Yoshimasa; Yamaguchi, Yuki; Handa, Hiroshi

    2010-03-12

    Half a century ago, thalidomide was widely prescribed to pregnant women as a sedative but was found to be teratogenic, causing multiple birth defects. Today, thalidomide is still used in the treatment of leprosy and multiple myeloma, although how it causes limb malformation and other developmental defects is unknown. Here, we identified cereblon (CRBN) as a thalidomide-binding protein. CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks. Thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting the associated ubiquitin ligase activity. This study reveals a basis for thalidomide teratogenicity and may contribute to the development of new thalidomide derivatives without teratogenic activity.

  16. Defibrotide blunts the prothrombotic effect of thalidomide on endothelial cells.

    Science.gov (United States)

    Echart, C L; Somaini, S; Distaso, M; Palumbo, A; Richardson, P G; Fareed, J; Iacobelli, M

    2012-01-01

    Patients with multiple myeloma (MM) are at relatively high risk of developing thromboembolic events such deep venous thrombosis (DVT) where thalidomide therapy has been identified to increase this risk. Defibrotide (DF), a polydisperse oligonucleotide, showed previously to counteract the alterations in endothelial cells (ECs) induced by lipopolysaccharide. It prompts us to investigate the impact of thalidomide on ECs and whether DF modulates changes in fibrinolysis induced by thalidomide. In this in vitro study, MM by itself alters the profibrinolytic potential of ECs decreasing the tissue plasminogen activator (t-PA) and increasing the plasminogen activator inhibitor 1 (PAI-1) levels which is potentiated by thalidomide. Defibrotide was able to counteract these effects. Additionally, DF upregulated the t-PA and downregulated PAI-1 gene expression modulated by thalidomide. Defibrotide also protects ECs from thalidomide-mediated cell death without interfering with its antitumor effects. These findings support DF clinical use for the prevention of DVT induced by immunomodulatory drugs.

  17. Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells.

    Science.gov (United States)

    Tachikawa, Saoko; Nishimura, Toshinobu; Nakauchi, Hiromitsu; Ohnuma, Kiyoshi

    2017-10-01

    Thalidomide, which was formerly available commercially to control the symptoms of morning sickness, is a strong teratogen that causes fetal abnormalities. However, the mechanism of thalidomide teratogenicity is not fully understood; thalidomide toxicity is not apparent in rodents, and the use of human embryos is ethically and technically untenable. In this study, we designed an experimental system featuring human-induced pluripotent stem cells (hiPSCs) to investigate the effects of thalidomide. These cells exhibit the same characteristics as those of epiblasts originating from implanted fertilized ova, which give rise to the fetus. Therefore, theoretically, thalidomide exposure during hiPSC differentiation is equivalent to that in the human fetus. We examined the effects of thalidomide on undifferentiated hiPSCs and early-differentiated hiPSCs cultured in media containing bone morphogenetic protein-4, which correspond, respectively, to epiblast (future fetus) and trophoblast (future extra-embryonic tissue). We found that only the number of undifferentiated cells was reduced. In undifferentiated cells, application of thalidomide increased the number of apoptotic and dead cells at day 2 but not day 4. Application of thalidomide did not affect the cell cycle. Furthermore, immunostaining and flow cytometric analysis revealed that thalidomide exposure had no effect on the expression of specific markers of undifferentiated and early trophectodermal differentiated cells. These results suggest that the effect of thalidomide was successfully detected in our experimental system and that thalidomide eliminated a subpopulation of undifferentiated hiPSCs. This study may help to elucidate the mechanisms underlying thalidomide teratogenicity and reveal potential strategies for safely prescribing this drug to pregnant women.

  18. New Rising Infection: Human Herpesvirus 6 Is Frequent in Myeloma Patients Undergoing Autologous Stem Cell Transplantation after Induction Therapy with Bortezomib

    Directory of Open Access Journals (Sweden)

    Netanel Horowitz

    2012-01-01

    Full Text Available Herpesvirus 6 (HHV-6 infection is a common complication during immunosuppression. Its significance for multiple myeloma (MM patients undergoing autologous stem cell transplantation (ASCT after treatment with novel agents affecting immune system remains undetermined. Data on 62 consecutive MM patients receiving bortezomib-dexamethasone (VD (; 66% or thalidomide-dexamethasone (TD (, 34% induction, together with melphalan 200 mg/m2 autograft between 01.2005 and 09.2010, were reviewed. HHV-6 reactivation was diagnosed in patients experiencing postengraftment unexplained fever (PEUF in the presence of any level of HHHV-6 DNA in blood. There were no statistically significant differences in patient characteristics between the groups, excluding dexamethasone dosage, which was significantly higher in patients receiving TD. Eight patients in TD and 18 in VD cohorts underwent viral screening for PEUF. HHV-6 reactivation was diagnosed in 10 patients of the entire series (16%, accounting for 35% of those screened; its incidence was 19.5% ( in the VD group versus 9.5% ( in the TD group. All patients recovered without sequelae. In conclusion, HHV-6 reactivation is relatively common after ASCT, accounting for at least a third of PEUF episodes. Further studies are warranted to investigate whether bortezomib has an impact on HHV-6 reactivation development.

  19. [Current therapeutic indications of thalidomide and lenalidomide].

    Science.gov (United States)

    Ordi-Ros, Josep; Cosiglio, Francisco Javier

    2014-04-22

    Thalidomide is a synthetic glutamic acid derivative first introduced in 1956 in Germany as an over the counter medications. It was thought to be one of the safest sedatives ever produced as it was effective in small doses, was not addictive, and did not have acute side-effects such as motor impairment, but was quickly removed from market after it was linked to cases of severe birth defects. The Food and Drug Administration approved use in the treatment of erythema nodosum leprosum. Further, it was shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell hystiocytosis, aphthous stomatitis, Behçet syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and others. In May 2006, it was approved for the treating multiple myeloma. New thalidomide analogues have been developed but lack clinical experience. This paper is a review of the history, pharmacology, mechanism of action, clinical applications and side effects of thalidomide and its analogues. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

  1. Thalidomide protects mice against LPS-induced shock

    Directory of Open Access Journals (Sweden)

    Moreira A.L.

    1997-01-01

    Full Text Available Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

  2. A Novel Green Synthesis of Thalidomide and Analogs

    Directory of Open Access Journals (Sweden)

    Ellis Benjamin

    2017-01-01

    Full Text Available Thalidomide and its derivatives are currently under investigation for their antiangiogenic, immunomodulative, and anticancer properties. Current methods used to synthesize these compounds involve multiple steps and extensive workup procedures. Described herein is an efficient microwave irradiation green synthesis method that allows preparation of thalidomide and its analogs in a one-pot multicomponent synthesis system. The multicomponent synthesis system developed involves an array of cyclic anhydrides, glutamic acid, and ammonium chloride in the presence of catalytic amounts of 4-N,N-dimethylaminopyridine (DMAP to produce thalidomide and structurally related compounds within minutes in good isolated yields.

  3. Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

    Directory of Open Access Journals (Sweden)

    Tatiana Barichello

    2011-01-01

    Full Text Available Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day. The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction.

  4. Impact of dexamethason

    Directory of Open Access Journals (Sweden)

    Zahra Basirat

    2016-09-01

    Full Text Available Objective: Infertile women with polycystic ovary (PCOs involve with anovulatory cycles. Various adjuvant treatments have been suggested to improve ovarian response in these patients. In this study, we aimed to evaluate the role of dexamethasone in the outcome of IVF/ICSI in PCOs infertile women. Study design: 129 PCOs infertile women undergone IVF/ICSI were enrolled for this single blind clinical trial study in 2012–2013. Setting: Fatemezahra Infertility and Reproductive Health Research Center, Babol University of Medical Sciences, Babol, Iran. Method: 43 patients who underwent IVF received dexamethasone (0.5 mg, 4 tab/day in the treatment group and 74 patients were considered as the placebo group. Main outcome measure: Pregnancy rate was compared between the two groups. In addition, number of dominant follicle, oocytes retrieved, embryos transferred, and number of gonadotropin ampoule were evaluated. Results: The pregnancy rate in the group receiving dexamethasone was 17.5% significantly higher versus 4.3% in the placebo group (P < 0.05. The mean number of embryos in the patients received dexamethasone was 6.7 ± 4.3, significantly greater than placebo which was 4.9 ± 4.9 (P < 0.05. The mean number of gonadotropin ampoules used in the group received dexamethasone was 3.5 ± 1.6, significantly lower versus the placebo which was 5.3 ± 2.5 (P < 0.05. The mean number of oocytes in the group received dexamethasone was 11.8 ± 8 and in the placebo group was 9.6 ± 5.8 that was not significant. Conclusion: Dexamethasone enhances embryos and pregnancy rate; in addition, it reduces gonadotropines ampoule used for stimulation, hence, and we recommend using of dexamethasone in women with PCOs undertreatment of IVF/ICSI.

  5. The Clinical Development of Thalidomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer

    National Research Council Canada - National Science Library

    Dlaiani, Danai

    2002-01-01

    ...), assessed by wound healing and peri-operative bleeding; 2) Efficacy of neo-adjuvant thalidomide treatment, as measured by the rate of tumor reduction I PSA decline while on thalidomide therapy; 3...

  6. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

    Science.gov (United States)

    San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

    2015-01-01

    Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

  7. Thalidomide has a significant effect in patients with thalassemia intermedia.

    Science.gov (United States)

    Li, YunShuan; Ren, Quan; Zhou, Yali; Li, Pingping; Lin, Wanhua; Yin, Xiaolin

    2018-01-01

    To investigate the effect of thalidomide in patients with thalassemia intermedia. We observed the effect of thalidomide in seven patients with thalassemia intermedia requiring blood transfusion. Four of the patients were transfusion-independent, and three patients were transfusion-dependent. For the four transfusion-independent patients, hemoglobin concentration increased significantly (≥2 g/dl) in three and moderately (1-2 g/dl) in one. After 3 months of treatment, hemoglobin concentration increased 3.2 ± 1.2 g/dl compared to pretreatment. Among the three transfusion-dependent patients, transfusion was terminated after one month of treatment in one patient and decreased >50% in the other two patients, accompanied by an increase in the average hemoglobin concentration. Thalidomide had a significant effect in patients with thalassemia intermedia. Further studies of a larger scale and more rigorous design are warranted.

  8. Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

    Science.gov (United States)

    Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

    2016-06-01

    Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

  9. Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver

    DEFF Research Database (Denmark)

    Møller, Lin Nanna Okholm; Knudsen, Anders Riegels; Andersen, Kasper Jarlhelt

    2015-01-01

    , high dose dexamethasone, low dose dexamethasone or placebo intravenously 18 h before laparotomy with subsequent 60 min of liver ischemia. After reperfusion for 24 h the animals had their liver removed. Bloods were drawn 30 min and 24 h post ischemia induction. Liver cell apoptosis and necrosis were...

  10. Safety of thalidomide in newly diagnosed elderly myeloma patients

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Waage, Anders; Hulin, Cyrille

    2013-01-01

    Background. Melphalan-prednisone-thalidomide (MPT) improves outcome in multiple myeloma (MM) patients, and it is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. Design and Methods. An individual patient data...

  11. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Hong-xia Xue

    2015-01-01

    Full Text Available Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  12. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis.

    Science.gov (United States)

    Xue, Hong-Xia; Fu, Wen-Yi; Cui, Hua-Dong; Yang, Li-Li; Zhang, Ning; Zhao, Li-Juan

    2015-05-01

    Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  13. Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.

    Science.gov (United States)

    Kwon, Jihyun; Min, Chang-Ki; Kim, Kihyun; Han, Jae-Joon; Moon, Joon Ho; Kang, Hye Jin; Eom, Hyeon-Seok; Kim, Min Kyoung; Kim, Hyo Jung; Yoon, Dok Hyun; Lee, Jeong-Ok; Lee, Won Sik; Lee, Jae Hoon; Lee, Je-Jung; Choi, Yoon-Seok; Kim, Sung Hyun; Yoon, Sung-Soo

    2017-01-01

    We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. The Rise, Fall and Subsequent Triumph of Thalidomide: Lessons Learned in Drug Development

    Science.gov (United States)

    Rehman, Waqas; Arfons, Lisa M.; Lazarus, Hillard M.

    2011-01-01

    Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and better understood. Ongoing research and development of related drugs such as lenalidomide now represent a class of irreplaceable drugs in hematological malignancies. Further, the tragedies associated with this agent stimulated the legislation which revamped the FDA regulatory process, expanded patient informed consent procedures and mandated more transparency from drug manufacturers. Finally, we review recent clinical trials summarizing selected medical indications for thalidomide with an emphasis on hematologic malignancies. Herein, we provide a historic perspective regarding the up-and-down development of thalidomide. Using PubMed databases we conducted searches using thalidomide and associated keywords highlighting pharmacology, mechanisms of action, and clinical uses. PMID:23556097

  15. Inhibition of DNA synthesis and radiosensitization effects of thalidomide on esophageal carcinoma TE1 cells

    International Nuclear Information System (INIS)

    Yu Jingping; Sun Suping; Sun Zhiqiang; Sun Meiling; Liu Fenju

    2010-01-01

    Objective: To explore the radiosensitization effect of thalidomide combined with X-ray on esophageal carcinoma TE1 cells. Methods: Cell scratch assay was used to detect the inhibition ability of different concentration of Thalidomide on cell invasion and metastasis. H 3 -TdR incorporation assay was used to investigate the inhibition of DNA synthesis in TE1 cells by treated with Thalidomide singly or combination with X-rays. The colony formation assay was used to analyze the radiosensitization of Thalidomide effect on TE1 cells. Results: Thalidomide had obvious inhibition effect on TE1 cell metastasis, DNA synthesis and colony formation, which were correlated with drug concentration. The values D 0 , D q and SF 2 in TE1 cells were gradually decreased with thalidomide concentration increased. When the concentration of thalidomide was 100μg/ml, the SER D 0 and SER D 0 and SER D q were (1.4±0.2) and (1.5±0.1), respectively, While the concentration of thalidomide was 150 μg/ml, the SER D 0 and SER D q were (1.5±0.2) and (1.8±0.2), respectively. Conclusions: Thalidomide could inhibit TE1 cell invasion, metastasis, DNA synthesis, and significantly enhance the radiosensitizing effect on esophageal carcinoma TE1 cells. (authors)

  16. Emerging role of thalidomide in the treatment of gastrointestinal bleeding.

    Science.gov (United States)

    McFarlane, Michael; O'Flynn, Lauren; Ventre, Rachel; Disney, Benjamin R

    2018-04-01

    Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.

  17. The efficacy and safety of the PAD regimen (bortezomib, doxorubicin, dexamethasone) in the treatment of plasma cell leukemia

    International Nuclear Information System (INIS)

    Kraj, M.; Poglod, R.; Szpila, T.; Warzocha, K.

    2009-01-01

    Plasma cell leukemia (PCL) represents the most aggressive variant of multiple myeloma that requires establishing new treatment approaches. Here, we report 4 patients with PCL treated with bortezomib. In 3 patients primary PCL and in one - secondary PCL was diagnosed. Two patients had previously received 2 to 4 lines of chemotherapy, including thalidomide and two patients received only VAD treatment. Bortezomib was given according to the standard schedule of 1.3 mg/m 2 days 1,4,8,11 with an interval of 10 days between the cycles. Three patients received doxorubicin 9 mg/m2 and dexamethasone 40 mg on days 1-4 of cycle in combination with bortezomib (PAD regimen). In the first patient with primary PCL (with bone marrow plasma cell ratio - 80%, absolute peripheral blood plasma cell count- 3.7 x 10 9 /L cells, IgGλ serum monoclonal protein 8.5 g/dL and osteolysis) bortezomib was administered twice as an induction therapy and was re-administered in relapse. A near complete remission (disappearance of circulating and bone marrow plasma cells, disappearance of M-component at electrophoresis but positive immunofixation) was achieved subsequently to induction PAD treatment. In this patient herpes zoster and neurological grade 2 toxicity was observed. Following cyclophosphamide 4.9 g and G-CSF, peripheral blood stem cells were successfully (8.0 x 10 6 CD34 + cells/kg) harvested. After melphalan 200 mg/m 2 peripheral blood autologous stem cell transplantation (PBASCT) was performed. The time to neutrophil > 0.5 x 10 9 /L engraftment was 20 days and the time to platelet count > 20 x 10 9 /L was 17 days. PBASCT led to complete remission which lasted 7 months. Partial remission was achieved subsequently to PCL relapse retreatment with PAD which was accompanied by hematological toxicity, infections and aggravation of peripheral sensory neuropathy. The patient died of progressive disease 27 months from PCL diagnosis and 8 months from its recurrence. In the second case of primary

  18. Effects of 5HPP-33,an antiangiogenic thalidomide analog, in mouse whole embryo culture

    Science.gov (United States)

    Thalidomide is a well-known example of a teratogen which has been shown to have an inhibitory effect on angiogenesis. As a result of its targeted effect on immature blood vessels, anti-angiogenic specific chemical analogs were developed to maximize this mechanism of thalidomide e...

  19. Effects of maternal dexamethasone exposure on hematological ...

    African Journals Online (AJOL)

    Exposure to dexamethasone at LD 1-14 and 1-21 significantly (P<0.05) reduced RBC and platelet counts but it raised MCV and MCH relative to control. This study suggests that prenatal and lactational dexamethasone administration may affect the hematological indices in the male offspring. Keywords: Dexamethasone ...

  20. Nitric oxide mediates the anticonvulsant effects of thalidomide on pentylenetetrazole-induced clonic seizures in mice.

    Science.gov (United States)

    Payandemehr, Borna; Rahimian, Reza; Gooshe, Maziar; Bahremand, Arash; Gholizadeh, Ramtin; Berijani, Sina; Ahmadi-Dastgerdi, Mohammad; Aminizade, Mehdi; Sarreshte-Dari, Ali; Dianati, Vahid; Amanlou, Massoud; Dehpour, Ahmad Reza

    2014-05-01

    Thalidomide is an old glutamic acid derivative which was initially used as a sedative medication but withdrawn from the market due to the high incidence of teratogenicity. Recently, it has reemerged because of its potential for counteracting number of diseases, including neurodegenerative disorders. Other than the antiemetic and hypnotic aspects, thalidomide exerts some anticonvulsant properties in experimental settings. However, the underlying mechanisms of thalidomide actions are not fully realized yet. Some investigations revealed that thalidomide could elicit immunomodulatory or neuromodulatory properties by affecting different targets, including cytokines (such as TNF α), neurotransmitters, and nitric oxide (NO). In this regard, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of thalidomide is affected through modulation of the l-arginine-nitric oxide pathway or not. Injection of a single effective dose of thalidomide (10 mg/kg, i.p. or higher) significantly increased the seizure threshold (P<0.05). On the one hand, pretreatment with low and per se noneffective dose of l-arginine [NO precursor] (10, 30 and 60 mg/kg) prevented the anticonvulsant effect of thalidomide. On the other hand, NOS inhibitors [l-NAME and 7-NI] augmented the anticonvulsant effect of a subeffective dose of thalidomide (1 and 5 mg/kg, i.p.) at relatively low doses. Meanwhile, several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of thalidomide significantly. In summary, our findings demonstrated that the l-arginine-nitric oxide pathway can be involved in the anticonvulsant properties of thalidomide, and the role of constitutive nNOS is prominent in the reported neuroprotective feature. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Thalidomide for control delayed vomiting in cancer patients receiving chemotherapy

    International Nuclear Information System (INIS)

    Han, Z.; Sun, X.; Du, X.

    2016-01-01

    To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. Study Design: Randomized, double-blind controlled study. Place and Duration of Study: The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. Methodology: A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the ?2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). Results: The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (?2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). Conclusion: Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.

  2. Comparative study of preoperative use of oral gabapentin, intravenous dexamethasone and their combination in gynaecological procedure

    Directory of Open Access Journals (Sweden)

    Neha Agrawal

    2015-01-01

    Full Text Available Background: We studied the effects of oral gabapentin and intravenous (I.V. dexamethasone given together or separately 1 h before the start of surgery on intraoperative hemodynamics Postoperative analgesia and postoperative nausea vomiting (PONV in patients undergoing gynaecological procedure. Materials and Methods: Patients were randomly divided into three groups: Group 1 (gabapentin, n = 46 received 400 mg gabapentin, Group 2 (dexamethasone, n = 46 received 8 mg dexamethasone and Group 3 (gabapentin plus dexamethasone, n = 46 received both 400 mg gabapentin and 8 mg dexamethasone I.V. 1 h before the start of surgery. Standard induction and maintenance of anesthesia were accomplished. Visual analog scale for pain was recorded for 12 h. Side effects were noted. Results: Hemodynamics at various time interval (0, 5, 10, 15, 20, 25 and 30 min of laryngeal mask airway insertion and PONV were found significantly lower in Group 3 than in Group 1 and Group 2 (P 3 was significantly longer in Group 3 (510.00 ± 61.64 min than in Group 1 (352.83 ± 80.61 min and in Group 2 (294.78 ± 60.76 min, (P < 0.05. Conclusion: The present study concludes that the combination of oral Gabapentin and I.V. dexamethasone has significantly less hemodynamic changes, better postoperative analgesia and less incidence of PONV than individual administration of each drug.

  3. The effect of single low-dose dexamethasone on vomiting during awake craniotomy.

    Science.gov (United States)

    Kamata, Kotoe; Morioka, Nobutada; Maruyama, Takashi; Komayama, Noriaki; Nitta, Masayuki; Muragaki, Yoshihiro; Kawamata, Takakazu; Ozaki, Makoto

    2016-12-01

    Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P awake craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.

  4. Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells

    Directory of Open Access Journals (Sweden)

    Madácsi Ramóna

    2010-06-01

    Full Text Available Abstract Background Cytoplasmic lipid-droplets are common inclusions of eukaryotic cells. Lipid-droplet binding thalidomide analogs (2,6-dialkylphenyl-4/5-amino-substituted-5,6,7-trifluorophthalimides with potent anticancer activities were synthesized. Results Cytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER, induction of reactive oxygen species (ROS, ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis. Conclusions Because of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.

  5. A novel brain trauma model in the mouse : effects of dexamethasone treatment

    NARCIS (Netherlands)

    Hortobágyi, Tibor; Hortobagyi, S; Gorlach, C; Harkany, T; Benbyo, Z; Gorogh, T; Nagel, W; Wahl, M

    2000-01-01

    We describe a novel methodological approach for inducing cold lesion in the mouse as a model of human cortical contusion trauma. To validate its reproducibility and reliability, dexamethasone (Dxm) was repeatedly applied to demonstrate possible antioedematous drug effects. Following tho induction of

  6. Treatment of Hepatic Epithelioid Hemangioendothelioma: Finding Uses for Thalidomide in a New Era of Medicine

    Directory of Open Access Journals (Sweden)

    Matthew P. Soape

    2015-01-01

    Full Text Available Hepatic epithelioid hemangioendothelioma (HEH is extremely rare, occurring in 1 to 2 per 100,000, with chemotherapy options not well defined. Our case involved a 49-year-old female who had hepatic masses and metastasis to the lungs with a liver biopsy revealing HEH. After developing a rash from sorafenib, thalidomide was started with the progression of disease stabilized. Resection is only an option in 10% of the cases; therefore, chemotherapy is the only line of treatment. Newer chemotherapy alternatives are targeting angiogenesis via the vascular endothelial growth factor. Thalidomide was first used as an antiemetic, but, sadly, soon linked to phocomelia birth defects. Given the mechanism of action against angiogenesis, thalidomide has a valid role in vascular tumors. In conclusion, the use of thalidomide as chemotherapy is novel and promising, especially in the setting of a rare vascular liver tumor such as HEH.

  7. Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

    Science.gov (United States)

    Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

    2009-07-01

    The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

  8. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Gao, Xiugong; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-01-01

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds

  9. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xiugong, E-mail: xiugong.gao@fda.hhs.gov; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-08-15

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.

  10. Thalidomide and the Titanic: reconstructing the technology tragedies of the twentieth century.

    Science.gov (United States)

    Annas, G J; Elias, S

    1999-01-01

    The Titanic has become a metaphor for the disastrous consequences of an unqualified belief in the safety and invincibility of new technology. Similarly, the thalidomide tragedy stands for all of the "monsters" that can be inadvertently or negligently created by modern medicine. Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. Although this indication is very restricted, thalidomide will be available for off-label uses once it is on the market. New laws regarding abortion and a new technology, ultrasound, make reasonable the approval of thalidomide for patients who suffer from serious conditions it can alleviate. In addition, the FDA and the manufacturer have proposed the most stringent postmarketing monitoring ever used for a prescription drug, including counseling, contraception, and ultrasonography in the event of pregnancy. The Titanic/thalidomide lesson for the FDA and public health is that rules and guidelines alone are not sufficient to guarantee safety. Continuous vigilance will be required to ensure that all reasonable postmarketing monitoring steps are actually taken to avoid predictable and preventable teratogenic disasters.

  11. Thalidomide and the Titanic: reconstructing the technology tragedies of the twentieth century.

    Science.gov (United States)

    Annas, G J; Elias, S

    1999-01-01

    The Titanic has become a metaphor for the disastrous consequences of an unqualified belief in the safety and invincibility of new technology. Similarly, the thalidomide tragedy stands for all of the "monsters" that can be inadvertently or negligently created by modern medicine. Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. Although this indication is very restricted, thalidomide will be available for off-label uses once it is on the market. New laws regarding abortion and a new technology, ultrasound, make reasonable the approval of thalidomide for patients who suffer from serious conditions it can alleviate. In addition, the FDA and the manufacturer have proposed the most stringent postmarketing monitoring ever used for a prescription drug, including counseling, contraception, and ultrasonography in the event of pregnancy. The Titanic/thalidomide lesson for the FDA and public health is that rules and guidelines alone are not sufficient to guarantee safety. Continuous vigilance will be required to ensure that all reasonable postmarketing monitoring steps are actually taken to avoid predictable and preventable teratogenic disasters. PMID:9987477

  12. Anti-inflammatory thalidomide improves islet grafts survival and functions in a xenogenic environment.

    Directory of Open Access Journals (Sweden)

    Chunguang Chen

    Full Text Available Thalidomide possesses both anti-inflammatory and anti-angiogenic properties. This study investigates its potential application in islet transplantation with a xenogenic transplantation model. Transplantation was performed using C57Bl/6 mice and NMRI nu/nu mice as recipients of porcine islets. Moreover, islet graft vasculature and inflammation were investigated to identify the mechanisms of thalidomide action. In the immunocompetent environment of C57Bl/6 mice, a fast graft rejection was observed. The group treated with thalidomide 200 mg/kg BW per day achieved and maintained euglycemia in the complete observation period for 42 days. The treated mice had more functional islet graft mass with less leukocyte infiltration. The pro-inflammatory TNF-alpha and VEGF content in islet grafted kidneys was significantly lowered by the treatment. By comparison, thalidomide was not effective in improving graft survival in immunocompromised nude mice. It strongly inhibited the VEGF and TNF-alpha-induced endothelial proliferation of isolated pig islets in a dose dependent manner. The magnitude of thalidomide's inhibitory effect was nearly identical to the effect of VEGF- receptor 2 inhibitor SU416 and anti-TNF-receptor 1 neutralizing antibody, and was reversed by sphingosine-1-phosphate. In conclusion, the anti-inflammatory effect of thalidomide improved islet graft survival and function in a transplantation model with a maximum immune barrier.

  13. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

    DEFF Research Database (Denmark)

    Zweegman, Sonja; van der Holt, Bronno; Mellqvist, Ulf-Henrik

    2016-01-01

    The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalid......The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone......, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen...... with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS...

  14. Thalidomide Induces Limb Anomalies by PTEN Stabilization, Akt Suppression, and Stimulation of Caspase-Dependent Cell Death▿

    OpenAIRE

    Knobloch, Jürgen; Schmitz, Ingo; Götz, Katrin; Schulze-Osthoff, Klaus; Rüther, Ulrich

    2007-01-01

    Thalidomide, a drug used for the treatment of multiple myeloma and inflammatory diseases, is also a teratogen that causes birth defects, such as limb truncations and microphthalmia, in humans. Thalidomide-induced limb truncations result from increased cell death during embryonic limb development and consequential disturbance of limb outgrowth. Here we demonstrate in primary human embryonic cells and in the chicken embryo that thalidomide-induced signaling through bone morphogenetic proteins (...

  15. Prophylactic antiemetic effects of midazolam, dexamethasone, and its combination after middle ear surgery

    International Nuclear Information System (INIS)

    Makhdoom, Naeem K; Farid, Magdy F

    2009-01-01

    To evaluate and compare the efficacy of the combination of midazolam and dexamethasone, with midazolam and dexamethasone alone, for the prevention of postoperative nausea and vomiting (PONV) in female patients undergoing middle ear surgery. A prospective, randomized, double-blind, placebo-controlled study in 80 female patients (mean age 32.6 years), undergoing middle ear surgery with general anesthesia at Ohud Hospital, Madina, Kingdom of Saudi Arabia from May 2007 to May 2008. Patients were classified into 4 groups. They received intravenous normal saline (S group), midazolam 0.075 mg/kg (M group), or dexamethasone 10 mg (D group), or a combination of midazolam and dexamethasone (MD group), before the induction of anesthesia. Postoperatively for 24 hours observation and assessment of nausea, vomiting, rescue anti-emetics, and side effects of the study drugs such as headache and drowsiness were carried out. There was a significant difference between the 4 groups. The MD group was the least to develop PONV compared to other groups (p<0.01). Regarding nausea, there was a non-significant difference between the 4 groups, although the MD group developed the least symptoms among the 4 groups, there were no significant differences in pain intensity and side effects such as, headache, dizziness, and drowsiness between the 4 groups. The combination of midazolam 0.075 mg/kg and dexamethasone 10 mg intravenously is better than either drug alone in reducing the incidence of PONV in female patients after middle ear surgery. (author)

  16. Effects of dexamethasone and pheniramine hydrogen maleate on stress response in patients undergoing elective laparoscopic cholecystectomy.

    Science.gov (United States)

    Karaman, Kerem; Bostanci, Erdal Birol; Aksoy, Erol; Ulas, Murat; Yigit, Tuba; Erdemli, Mehmet Ozcan; Ercin, Ugur; Bilgihan, Ayse; Saydam, Gul; Akoglu, Musa

    2013-02-01

    Laparoscopic cholecystectomy (LC) still leads to significant postoperative nausea and vomiting (PONV) and pain. Our aim was to evaluate the efficacy of dexamethasone or pheniramine hydrogen maleate, either alone or combined, in reducing the stress response and symptoms after LC. Patients were randomly assigned to 1 of 4 groups, each consisting of 20 patients: control, dexamethasone (8 mg/2 mL), pheniramine hydrogen maleate (45.5 mg/2 mL), and the combined group. The drugs were given before anesthesia induction. C-reactive protein levels (CRP) and visual analog scale (VAS) scores were significantly less in the dexamethasone (P = .003) and combined groups (P pheniramine hydrogen maleate (P = .005) significantly reduced PONV. Dexamethasone significantly reduced postoperative pain and the systemic acute-phase response, whereas these effects were only partially attained with pheniramine hydrogen maleate. Both dexamethasone and pheniramine hydrogen maleate significantly reduced PONV. An additive effect seemed to occur if these drugs were used in combination. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Time to spare newly diagnosed non transplant eligible myeloma (ENDMM) from thalidomide

    DEFF Research Database (Denmark)

    Demarquette, H.; Guidez, S.; Jurczyszyn, A. J.

    2015-01-01

    group, all patients had bortezomib upfront, patients received Vd, VCd or VMP upfront; lenalidomide was then given at first relapse to all patients. The median dose administered of bortezomib was 1.3mg/m2, for a median of 5 cycles (2-9). Results. Overall, the median age was 73 years (range, 65 - 85......), with 35% aged >75. The M/F ratio was 1.1, 38% were ISS 3, the median b2m was 5.5mg/L, 26% had an ECOG score > 2, 42% had renal insufficiency, 11% had elevated LDH, 8% presence of plasmacytoma, and 14% had adverse FISH (del17p, t(4;14) and or t(14;16)). There was no difference in patients' characteristics......,2% were in the thalidomide upfront exposed arm and 53,8% had never been exposed to thalidomide. Patients were required to be aged >65 years, NDMM treated with either thalidomide upfront or never been exposed to thalidomide upfront or later in the myeloma disease course. If not exposed to thalidomide...

  18. Magnetic resonance imaging for monitoring the effects of thalidomide on experimental human breast cancers

    International Nuclear Information System (INIS)

    Cyran, Clemens C.; Sennino, Barbara; McDonald, Donald M.; Chaopathomkul, Bundit; Fu, Yanjun; Rogut, Victor S.; Shames, David M.; Wendland, Michael F.; Brasch, Robert C.

    2009-01-01

    Thalidomide, which inhibits angiogenesis in certain tumor types, reduced extravasation of a macromolecular contrast medium (MMCM) in a human breast cancer model as assayed by MMCM-enhanced dynamic magnetic resonance imaging (MRI) and fluorescence microscopy in the same tumors. After a 1-week, three-dose course of thalidomide, the mean MRI-assayed endothelial transfer coefficient, K PS , decreased significantly (p 3 . Correspondingly, microscopic measurements of extravasated MMCM, expressed as fractional area of streptavidin staining, were significantly (p PS values correlated significantly (r 2 =0.55, p<0.05) with microscopic measures of MMCM extravasation. However, no significant differences were observed between saline- and thalidomide-treated tumors with respect to rate of growth, vascular richness, or amount of VEGF-containing cells. Because of its sensitivity to the detection of changes in vascular leakage in tumors, this MMCM-enhanced MRI assay could prove useful for monitoring the effects of thalidomide on an individual patient basis. The significant correlation between MRI and fluorescence microscopic measures of MMCM extravasation supports the utility of the non-invasive MRI approach for assessing the action of thalidomide on tumor blood vessels. (orig.)

  19. Follow-up of Thalidomide treatment in patients with Hereditary Haemorrhagic Telangiectasia.

    Science.gov (United States)

    Hosman, A; Westermann, C J J; Snijder, R; Disch, F; Mummery, C L; Mager, J J

    2015-12-01

    Patients with a hereditary vascular disorder called Rendu-Osler-Weber syndrome (Hereditary Haemorrhagic Telangiectasia, HHT) haemorrhage easily due to weak-walled vessels. Haemorrhage in lungs or brain can be fatal but patients suffer most from chronic and prolonged nosebleeds (epistaxis), the frequency and intensity of which increases with age. Several years ago, it was discovered serendipitously that the drug Thalidomide had beneficial effects on the disease symptoms in several of a small group of HHT patients: epistaxis and the incidence of anaemia were reduced and patients required fewer blood transfusions. In addition, they reported a better quality of life. However, Thalidomide has significant negative side effects, including neuropathy and fatigue. We followed up all HHT patients in the Netherlands who had been taking Thalidomide at the time the original study was completed to find out (i) how many had continued taking Thalidomide and for how long (ii) the nature and severity of any side-effects and (iii) whether side-effects had influenced their decision to continue taking Thalidomide. Only a minority of patients had continued taking the drug despite its beneficial effects on their symptoms and that the side effects were the primary reason to stop. Despite symptom reduction, alternative treatments are still necessary for epistaxis in HHT patients and a large-scale clinical trial is not justified although incidental use in the most severely affected patients can be considered.

  20. The Molecular Mechanisms of Thalidomide Teratogenicity and Implications for Modern Medicine.

    Science.gov (United States)

    Knobloch, J; Jungck, D; Koch, A

    2017-01-01

    Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and antiangiogenic activities are considered in many other refractory diseases. The aim is to develop derivatives that are not teratogenic but maintain the therapeutic potential. This requires detailed knowledge about the underlying molecular mechanisms. Much progress has been made in deciphering the teratogenic mechanisms in the last decade. Here, we summarize these mechanisms, explain thalidomide resistance of rodents, and discuss possible mechanisms that could explain why the drug primarily targets the developing limb in the embryo. We also summarize the most important therapeutic mechanisms. Finally, we discuss which therapeutic and teratogenic mechanisms do and do not overlap, and if there is a chance for the development of non-teratogenic thalidomide derivatives with therapeutic potential. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Dexamethasone

    Science.gov (United States)

    ... during periods of stress (injuries, infections, and severe asthma attacks). Ask your pharmacist or doctor how to obtain ... sputum (the matter you cough up during an asthma attack) thickens or changes color from clear white to ...

  2. Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.

    Science.gov (United States)

    Rodrigues, Gustavo Büchele; Passos, Giselle Fazzioni; Di Giunta, Gabriella; Figueiredo, Cláudia Pinto; Rodrigues, Eduardo Büchele; Grumman, Astor; Medeiros, Rodrigo; Calixto, João B

    2007-03-01

    The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

  3. Comparison the Effect of Granisetron and Dexamethasone on Intravenous Propofol Pain

    Science.gov (United States)

    Adinehmehr, Leili; Salimi, Sohrab; Sane, Shahryar; Sina, Venous; Najafizadeh, Rana

    2018-01-01

    Background: The incidence of propofol injection pain during induction of general anesthesia varies from 28% to 90%. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexamethasone and granisetron for reducing the incidence and severity of propofol injection pain. Materials and Methods: A total of 227 female subjects received 5 mL of preservative-free saline, 1 mg granisetron (5 ml), or 0.15 mg/kg of dexamethasone (5 ml), intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg/kg injection of propofol. Pain scores and intensity of pain recorded immediately following the injection of propofol. Hemodynamic parameters and O2 sat were recorded 1, 3, 5, and 10 min after propofol injection. Results: The incidence pain following the injection of propofol was significantly decreased with both granisetron and dexamethasone (50.7% and 49.4%). Mean pain score in granisetron group was 3.16 ± 1.23, dexamethasone was 2.73 ± 1.03, and in saline group was 4.82 ± 1.73 (P = 0.001). Mean pain intensity in granisetron group was 1.16 ± 0.18, dexamethasone was 1.26 ± 0.14, and in saline group was 2.2 ± 0.99 (P = 0.001). There were no differences in either mean arterial pressure or O2 Sate at any time point after drugs injection among the groups. There was a significant difference in pulse rate in third minutes between three groups and in the group who received granisetron was lesser (P = 0.04). Conclusion: Pretreatment with intravenous granisetron (1 mg) and dexamethasone (0.15 mg/kg) before injection of propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection. PMID:29862223

  4. Comparison the Effect of Granisetron and Dexamethasone on Intravenous Propofol Pain.

    Science.gov (United States)

    Adinehmehr, Leili; Salimi, Sohrab; Sane, Shahryar; Sina, Venous; Najafizadeh, Rana

    2018-01-01

    The incidence of propofol injection pain during induction of general anesthesia varies from 28% to 90%. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexamethasone and granisetron for reducing the incidence and severity of propofol injection pain. A total of 227 female subjects received 5 mL of preservative-free saline, 1 mg granisetron (5 ml), or 0.15 mg/kg of dexamethasone (5 ml), intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg/kg injection of propofol. Pain scores and intensity of pain recorded immediately following the injection of propofol. Hemodynamic parameters and O 2 sat were recorded 1, 3, 5, and 10 min after propofol injection. The incidence pain following the injection of propofol was significantly decreased with both granisetron and dexamethasone (50.7% and 49.4%). Mean pain score in granisetron group was 3.16 ± 1.23, dexamethasone was 2.73 ± 1.03, and in saline group was 4.82 ± 1.73 ( P = 0.001). Mean pain intensity in granisetron group was 1.16 ± 0.18, dexamethasone was 1.26 ± 0.14, and in saline group was 2.2 ± 0.99 ( P = 0.001). There were no differences in either mean arterial pressure or O 2 Sate at any time point after drugs injection among the groups. There was a significant difference in pulse rate in third minutes between three groups and in the group who received granisetron was lesser ( P = 0.04). Pretreatment with intravenous granisetron (1 mg) and dexamethasone (0.15 mg/kg) before injection of propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection.

  5. Comparison the Effect of Granisetron and Dexamethasone on Intravenous Propofol Pain

    Directory of Open Access Journals (Sweden)

    Leili Adinehmehr

    2018-01-01

    Full Text Available Background: The incidence of propofol injection pain during induction of general anesthesia varies from 28% to 90%. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexamethasone and granisetron for reducing the incidence and severity of propofol injection pain. Materials and Methods: A total of 227 female subjects received 5 mL of preservative-free saline, 1 mg granisetron (5 ml, or 0.15 mg/kg of dexamethasone (5 ml, intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg/kg injection of propofol. Pain scores and intensity of pain recorded immediately following the injection of propofol. Hemodynamic parameters and O2sat were recorded 1, 3, 5, and 10 min after propofol injection. Results: The incidence pain following the injection of propofol was significantly decreased with both granisetron and dexamethasone (50.7% and 49.4%. Mean pain score in granisetron group was 3.16 ± 1.23, dexamethasone was 2.73 ± 1.03, and in saline group was 4.82 ± 1.73 (P = 0.001. Mean pain intensity in granisetron group was 1.16 ± 0.18, dexamethasone was 1.26 ± 0.14, and in saline group was 2.2 ± 0.99 (P = 0.001. There were no differences in either mean arterial pressure or O2Sate at any time point after drugs injection among the groups. There was a significant difference in pulse rate in third minutes between three groups and in the group who received granisetron was lesser (P = 0.04. Conclusion: Pretreatment with intravenous granisetron (1 mg and dexamethasone (0.15 mg/kg before injection of propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection.

  6. A Phase II dose titration study of thalidomide for cancer-associated anorexia.

    Science.gov (United States)

    Davis, Mellar; Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Bicanovsky, Leslie; Lagman, Ruth

    2012-01-01

    Sixty-five percent of people with advanced cancer suffers from loss of appetite. Several inflammatory cytokines appear to cause appetite loss in animal models. Thalidomide is an immunomodulatory drug that has been associated with improved appetite in those with HIV infections and cancer. We completed a two-stage Phase II dose titration study of thalidomide, the primary purpose of which was to assess appetite response to thalidomide in cancer-associated anorexia. Individuals older than 18 years of age with active cancer, loss of appetite by numerical rating scale (NRS), life expectancy of at least four weeks, and Eastern Cooperative Oncology Group performance status of 0-3 were entered into the study. Pretreatment screening included medical history, neurologic examination, and symptoms by NRS and categorical scale (CAT). Patients received 50mg of thalidomide by mouth at bedtime for two weeks. Individuals who did not respond were dose escalated to 100mg at night for two weeks. Assessment of appetite, early satiety, fatigue, insomnia, night sweats, pain, and quality of life (QOL) occurred at two-week intervals. Toxicity also was assessed. The primary outcome was appetite response defined as a two-point reduction in the NRS or a one-point improvement in the CAT. Thirty-five patients entered the study; 33 completed 14 days of therapy and were analyzed for efficacy and toxicity. Sixty-four percent who completed at least two weeks of thalidomide had improved appetite. The CAT scores for appetite, insomnia, and QOL improved significantly. The 95% confidence intervals did not overlap. Five participants dropped out because of toxicity: two before two weeks and three later. Thalidomide reduced multiple symptoms commonly associated with cancer-related anorexia and improved QOL. Our findings confirmed and validated a previously published single-arm trial. A recent randomized trial demonstrated greater benefits when thalidomide is used combined with other agents to treat cancer

  7. The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients.

    Science.gov (United States)

    Murphy, Glenn S; Szokol, Joseph W; Avram, Michael J; Greenberg, Steven B; Shear, Torin; Vender, Jeffery S; Gray, Jayla; Landry, Elizabeth

    2014-06-01

    The effect of single low-dose dexamethasone therapy on perioperative blood glucose concentrations has not been well characterized. In this investigation, we examined the effect of 2 commonly used doses of dexamethasone (4 and 8 mg at induction of anesthesia) on blood glucose concentrations during the first 24 hours after administration. Two hundred women patients were randomized to 1 of 6 groups: Early-control (saline); Early-4 mg (4 mg dexamethasone); Early-8 mg (8 mg dexamethasone); Late-control (saline); Late-4 mg (4 mg dexamethasone); and Late-8 mg (8 mg dexamethasone). Blood glucose concentrations were measured at baseline and 1, 2, 3, and 4 hours after administration in the early groups and at baseline and 8 and 24 hours after administration in the late groups. The incidence of hyperglycemic events (the number of patients with at least 1 blood glucose concentration >180 mg/dL) was determined. Blood glucose concentrations increased significantly over time in all control and dexamethasone groups (from median baselines of 94 to 102 mg/dL to maximum medians ranging from 141 to 161.5 mg/dL, all P < 0.001). Blood glucose concentrations did not differ significantly between the groups receiving dexamethasone (either 4 or 8 mg) and those receiving saline at any measurement time. The incidence of hyperglycemic events did not differ in any of the early (21%-28%, P = 0.807) or late (13%-24%, P = 0.552) groups. Because blood glucose concentrations during the first 24 hours after administration of single low-dose dexamethasone did not differ from those observed after saline administrations, these results suggest clinicians need not avoid using dexamethasone for nausea and vomiting prophylaxis out of concerns related to hyperglycemia.

  8. Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury

    International Nuclear Information System (INIS)

    Anscher, Mitchell S.; Garst, Jennifer; Marks, Lawrence B.; Larrier, Nicole; Dunphy, Frank; Herndon, James E.; Clough, Robert B.S.; Marino, Christine R.N.; Vujaskovic, Zeljko; Zhou, Sumin; Dewhirst, Mark W.; Shafman, Timothy D.; Crawford, Jeffrey

    2006-01-01

    Purpose: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. Methods and Materials: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status ≥70, and life expectancy ≥6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m 2 ) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. Results: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. Conclusions: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity

  9. Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

    Science.gov (United States)

    Barea, Silvana A; Mattos, Cristiane B; Cruz, Ariadne C C; Chaves, Vitor C; Pereira, Rafael N; Simões, Claudia M O; Kratz, Jadel M; Koester, Letícia S

    2017-03-01

    Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire ® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor ® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.

  10. Granistron and dexamethasone provide more improved prevention of postoperative emesis than granisetron alone in children.

    Science.gov (United States)

    Fujii, Y; Tanaka, H; Toyooka, H

    1996-12-01

    Dexamethasone decreases chemotherapy-induced emesis when added to antiemetic regimens. This study was designed to compare the effectiveness of granisetron and dexamethasone with granisetron alone in the prevention of post-operative vomiting after strabismus repair, tonsillectomy with or without adenoidectomy in children. In a randomized, double-blind study, 60 healthy children, 4-10 yr of age, received either granisetron 40 micrograms.kg-1 and saline (Group S) or granisetron 40 micrograms.kg-1 and dexamethasone 4 mg (Group D) iv immediately after the induction of anaesthesia. All subjects received anaesthetics consisting of sevoflurane and nitrous oxide in oxygen Postoperative pain was treated with acetaminophen pr or pentazocine iv. Postoperatively, during the first 24 hr after anaesthesia, the frequencies of retching and vomiting, and the incidence of adverse events were recorded by nursing staff. There were no differences between the treatment groups with regard to demographics, surgical procedure, anaesthetic administered or analgesics used for postoperative pain. The frequency of the symptoms was 27% and 7% in Groups S and D, respectively (P < 0.05). The incidence of adverse events was comparable in the two groups. The prophylactic administration of granisetron and dexamethasone was more effective than granisetron alone in the prevention of postoperative vomiting in paediatric subjects undergoing strabismus repair, tonsillectomy and adenoidectomy.

  11. Efficacy of thalidomide in a girl with inflammatory calcinosis, a severe complication of juvenile dermatomyositis

    Directory of Open Access Journals (Sweden)

    Inayama Yoshiaki

    2010-02-01

    Full Text Available Abstract We report a 14-year-old girl with juvenile dermatomyositis (JDM complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions.

  12. Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Michelle S. Boyar

    2008-01-01

    Full Text Available We assessed the efficacy of combined temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma in a phase II single-institution trial. Twenty-four patients were enrolled. Temozolomide (150 mg/m2/day for 7 days every other week was administered with concomitant thalidomide (200 mg/day, and continued until unacceptable toxicity or disease progression. There were no complete responses and two (10% partial responses. Five patients (24% had stable disease for at least six months. Fourteen patients (67% progressed after a median of two-month treatment. The median overall survival (twenty-two assessable patients was 9.5 months [95% CI 7–28 months]. There were no treatment-related deaths or CTC grade 4 toxicities. Thirteen patients were dose-reduced or discontinued thalidomide due to toxicity. In conclusion, this combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with advanced leiomyosarcoma. We hypothesize that temozolomide is the active agent in this regimen, and should be further studied.

  13. Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

    2014-01-01

    Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six e...

  14. Thalidomide for Epistaxis in Patients with Hereditary Hemorrhagic Telangiectasia: A Preliminary Study.

    Science.gov (United States)

    Fang, Jia; Chen, Xiaomeng; Zhu, Bijun; Ye, Haibo; Zhang, Weitian; Guan, Jian; Su, Kaiming

    2017-08-01

    To evaluate the effectiveness of thalidomide for epistaxis in hereditary hemorrhagic telangiectasia (HHT), 7 HHT patients with recurrent epistaxis were treated with thalidomide at an initial dose of 50 mg/d, gradually increasing to 100 mg/d if needed. The Epistaxis Severity Score (ESS) was used to evaluate the treatment effects. Patients reported that epistaxis improved 1 to 3 weeks after starting thalidomide. The mean ESS before treatment, at the end of treatment, and 3 months after stopping treatment was 5.03 ± 2.05, 0.90 ± 0.84 ( P = .003), and 1.98 ± 1.33 ( P = .006), respectively. Four patients reported mild to moderate side effects, including drowsiness, dizziness, constipation, nausea, and peripheral neuropathy. Two patients stopped the treatment because of adverse effects. Those results showed that thalidomide may be a treatment choice for recurrent epistaxis in HHT patients, although the side effects should be considered. Further study should focus on guidelines for dosing and course and investigate how to reduce the adverse effects.

  15. O renascimento de um fármaco: talidomida The rebirth of a drug: thalidomide

    Directory of Open Access Journals (Sweden)

    Lídia Moreira Lima

    2001-10-01

    Full Text Available Thalidomide, first synthesized in 1953, was widely prescribed for morning sickness of pregnant women from 1957 to 1961, when it was found to be seriously teratogenic, having caused serious birth defect. Nowadays, a quarter of a century later, it appears that it may be a miracle drug for such diseases as leprosy, AIDS, cancer and tuberculosis.

  16. The use of dexamethasone in animals: implication for fertility ...

    African Journals Online (AJOL)

    Exposure to dexamethasone causes numerous changes in various biological systems including the reproductive system and this has huge implication on fertility and pregnancy. Maternal dexamethasone administration promotes foetal lung maturation and thermoregulation in premature foetuses. This indication makes ...

  17. The role of dexamethasone in peripheral and neuraxial nerve blocks ...

    African Journals Online (AJOL)

    pain and prolongs analgesia in the postoperative period when combined with ... management of acute pain and that focused on dexamethasone's ability to prolong ... of dexamethasone to brachial plexus nerve blocks and Akram and Hassani ...

  18. Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Ch’ang, Hui-Ju; Hsu, Chiun; Chen, Chien-Hung; Chang, Ya-Hui; Chang, Jeffrey S.; Chen, Li-Tzong

    2012-01-01

    Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 ± 48.9 vs. 148 ± 6.2 days, p = .15), or median overall survival (258 ± 45.6 vs. 241 ± 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-α levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1 month after RT

  19. Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ch' ang, Hui-Ju, E-mail: hjmc@nhri.org.tw [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan (China); Hsu, Chiun [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Chien-Hung [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Chang, Ya-Hui; Chang, Jeffrey S. [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Chen, Li-Tzong [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan (China)

    2012-02-01

    Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 {+-} 48.9 vs. 148 {+-} 6.2 days, p = .15), or median overall survival (258 {+-} 45.6 vs. 241 {+-} 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-{alpha} levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1

  20. Analgesic effects of dexamethasone in burn injury

    DEFF Research Database (Denmark)

    Werner, Mads U; Lassen, Birgit Vibeke; Kehlet, Henrik

    2002-01-01

    and secondary hyperalgesia. RESULTS: The burn injury induced significant increases in erythema (P burn did not differ between dexamethasone and placebo treatments (P >.6). There were no significant......BACKGROUND AND OBJECTIVES: Glucocorticoids are well-known adjuvant analgesics in certain chronic pain states. There is, however, a paucity of data on their analgesic efficacy in acute pain. Therefore, the aim of the study was to examine the analgesic effects of dexamethasone in a validated burn...... model of acute inflammatory pain in humans. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Intravenous dexamethasone 8 mg or placebo was administered on 2 separate study days. Two hours after drug administration, a first-degree burn...

  1. Dexamethasone for pain after outpatient shoulder surgery

    DEFF Research Database (Denmark)

    Bjørnholdt, K. T.; Mønsted, P. N.; Søballe, Kjeld

    2014-01-01

    Background Dexamethasone has analgesic properties when given intravenously before surgery, but the optimal dose has not been determined. We hypothesised that a dose of 40 mg dexamethasone would improve analgesia after outpatient shoulder surgery compared with 8 mg. Methods A randomised, double...... a dose–response relationship, increasing the dexamethasone dose from 8 to 40 mg did not improve analgesia significantly after outpatient shoulder surgery.......) or placebo (D0) before surgery. The primary outcome was pain intensity 8 h after surgery rated on a numeric rating scale of 0 to 10. Secondary outcomes were pain intensity, analgesic consumption and side effects during the first 3 days after surgery. Results Data from 73 patients were available for analysis...

  2. Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study.

    Science.gov (United States)

    Sethi, Rakesh; Naqash, Imtiaz A; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

    2016-01-01

    The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only.

  3. A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

    International Nuclear Information System (INIS)

    Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

    2008-01-01

    Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects

  4. A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide

    Directory of Open Access Journals (Sweden)

    Paiva Renata T

    2012-06-01

    Full Text Available Abstract Background Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide. Results We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR. Conclusions The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.

  5. Dexamethasone Therapy for Bacterial Meningitis: Better Never Than Late?

    Directory of Open Access Journals (Sweden)

    Susan M King

    1994-01-01

    Full Text Available A multicentre randomized controlled trial was conducted in children with bacterial meningitis using dexamethasone or placebo for four days within 24 h of starting antibiotics. Primary outcomes were hearing loss and neurological abnormalities at 12 months after meningitis. The dexamethasone (n=50 and placebo (n=51 groups were similar in age, severity of illness and etiological agent. Hearing loss occurred in 10% and 11% of the dexamethasone and placebo groups and neurological deficits occurred in 20% and 18% of patients, respectively. Duodenal perforation occurred in one dexamethasone-treated child. In conclusion, there was no significant benefit in those receiving dexamethasone. The lack of benefit may have been due to the delay in administration of dexamethasone (median delay of 11 h after antibiotics. Therefore, if dexamethasone is used for meningitis it should be given immediately with the antibiotic.

  6. Pinoresinol diglucoside exhibits protective effect on dexamethasone ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of pinoresinol diglucoside (PDG) on dexamethasone-induced osteoporosis in rats. Methods: Sixty Wistar rats were randomly and equally divided into normal, control, alendronate and PDG (10, 20 or 40 mg/kg) groups. Bone tissue parameters, including length, transverse diameter, weight, ...

  7. Effects of dexamethasone on brain edema

    International Nuclear Information System (INIS)

    Takemoto, Motohisa

    1982-01-01

    Experimental cerebral edema was produced on the right parietal lobe of Wistar male rats with a cold metal probe cooled by liquid nitrogen. Twenty hour later, 3 H-dexamethasone was either intramuscularly or intravenously injected into rats, estimated in the brain tissue by the liquid scintillation counting method. Edematous brain generally contained much higher 3 H-activity than the control. Furthermore, I.V. injection showed higher 3 H-activity than I.M injection in edematous and control brains at all times. For examination of the subcellular distribution of 3 H-dexamethasone in edematous brain, 3 H-activity was most strongly detected in the supernatant fraction (63%), followed by the heavy mitochondrial fraction (25.4%) and the nuclear fraction (8.4%). Although edematous brain tissue constantly demonstrated higher 3 H-activity than the control, its supernatant fraction conversely had less activity. As a next step, distribution of 3 H-dexamethasone in the supernatant fraction was studies. The result was that the high molecular weight fraction in the edematous brain showed higher radioactivity than the control. From these findings, unequivocal distribution of dexamethasone in the supernatant fraction of edematous brain tissue could be correlated with its biochemical action for preventing brain edema. (J.P.N.)

  8. Postoperative nausea and vomiting prophylaxis: A comparative study of ondansetron, granisetron and granisetron and dexamethasone combination after modified radical mastectomy

    Directory of Open Access Journals (Sweden)

    Pushplata Gupta

    2014-01-01

    Full Text Available Background: Post-operative nausea and vomiting (PONV is commonly seen after modified radical mastectomy (MRM. In this randomized double-blind prospective study we compared the efficacy of ondansetron, granisetron and granisetron and dexamethasone combination for prevention of PONV following MRM in female patients. Materials and Methods: A total of 75 patients (20-60 years of age undergoing elective MRM were randomly allocated to one of the three groups of 25 patients each. Group O received ondansetron 4 mg, Group G received granisetron 40 mcg/kg and group granisetron and dexamethasone (G + D received granisetron 40 mcg/kg + dexamethasone 8 mg prior to induction. All episodes of PONV within 24 h after induction of anesthesia were recorded. Statistical Analysis: Statistical analysis was done using Kruskal-Wallis test (nonparametric ANOVA. Results: The incidence of complete response (no PONV, no rescue medication was 96% with G+D, as compared with 86% with granisetron and 4% with ondansetron during 0-3h after surgery which was clinically significant (P < 0.05. Similarly clinically significant response was seen during 3-6, 6-9, 9-12 and 12-24 h of surgery. Conclusion: Granisetron and dexamethasone combination is more effective for prevention of PONV in comparison to individual ondansetron and granisetron in MRM.

  9. Mullerian agenesis associated with in-utero thalidomide exposure: A case report

    Directory of Open Access Journals (Sweden)

    Sarah Dotters-Katz

    2013-09-01

    Full Text Available Thalidomide is a well-known teratogen, which is experiencing resurgence as new uses are identified. Exposure is classically associated with limb deformities, such as: dysmelia, phocomelia, preaxial hypoplasia and polydactyly, in addition to visceral anomalies that have been documented as well. We report a case of a 38 year-old nulligravid female, who was previously evaluated for primary amenorrhea, and given the presumptive false diagnosis of an imperforate hymen. On magnetic resonance imaging (MRI exam, she was noted to have uterovaginal agenesis. The implications of thalidomide on women’s health extend beyond external birth defects. Although, most commonly associated with limb deformities, there may also be gynecologic implications of in utero exposure. As this medication is increasingly used for various medical conditions, obstetricians/gynecologists need to remain aware of this potential mullerian teratogenic effect.

  10. Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide?

    DEFF Research Database (Denmark)

    Beksac, Meral; Waage, Anders; Bringhen, Sara

    2015-01-01

    of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP...... ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor...

  11. The influence of dexamethasone and ketolgan on postoperative nausea and vomiting and estimation of risk factors in women undergoing gynecologic laparoscopic surgeries.

    Science.gov (United States)

    Rimaitis, Kestutis; Svitojūte, Asta; Macas, Andrius

    2010-01-01

    The aim of this study was to determine the effect of dexamethasone and ketolgan on postoperative nausea and vomiting and to evaluate risk factors for postoperative nausea and vomiting. A prospective, double-blind, randomized clinical study was carried out. One hundred fifty-three ASA I-II women undergoing laparoscopic gynecologic operations were randomized into three groups: dexamethasone group (n=51), ketolgan group (n=51), and control group (n=51). Patients in the dexamethasone group were given 4 mg of dexamethasone intravenously before the induction of general anesthesia, the ketolgan group received 30-mg ketolgan intravenously, and control group did not receive any medication. The incidence and severity of postoperative nausea and vomiting were registered 24 hours after the surgery. The incidence of postoperative nausea and vomiting in the dexamethasone group was 13.8%; in the ketolgan group, 37.3%, and in the control group, 58.9% (P=0.026). Patients with a history of migraine suffered from postoperative nausea and vomiting in 70.3% of cases and migraine-free patients in 25.8% of cases (P=0.015). Opioids for postoperative analgesia increased the incidence of postoperative nausea and vomiting as compared with nonsteroidal anti-inflammatory drugs (P=0.00002). Preoperative medication with dexamethasone significantly reduces the incidence of postoperative nausea and vomiting. Avoidance of opioids for postoperative analgesia reduces the incidence of postoperative nausea and vomiting. Migraine and motion sickness are independent risk factors for postoperative nausea and vomiting.

  12. Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

    Directory of Open Access Journals (Sweden)

    T.B.M. Castro

    2016-01-01

    Full Text Available In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61% vs 23 (39% males, and of whites, 49 (83.1% vs 10 (16.9% blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6. Regarding staging at diagnosis, 27 (45.7% patients were in stage III-A, with 12 (20.3% patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40 were: neutropenia (42.5%, diarrhea (47.5%, and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26 and sc (n=14 administration routes (P=0.343. In the group treated with thalidomide (n=19, 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038. Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%. Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

  13. Results of three-dimensional conformal radiotherapy and thalidomide for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hsu, Wei-Chung; Chung, Na-Na; Wang, Po-Ming; Ying, Kung-Shih; Shin, Jeng-Shiann; Chao, Che-Jen; Lin, Gau-De; Chan, Sue-Ching; Ting, Lai-Lei

    2006-01-01

    The purpose of this study was to evaluate the effectiveness of three-dimensional conformal radiotherapy and thalidomide in the treatment of advanced hepatocellular carcinoma. Between 1999 and 2003, 121 patients (mean age, 54.4±12.4 years; range, 20-81 years) with advanced hepatocellular carcinoma received three-dimensional conformal radiotherapy and thalidomide. Radiation was delivered in 1.5 Gy fractions twice daily for 5 days a week, for a total dose of 45-75 Gy. Mean treatment volume was 429.52±408.50 cm 3 (range, 26.89-2284.82 cm 3 ). Thalidomide was given concomitantly: 200 mg/day in 109 patients, 300 mg/day in 8 patients and 400 mg/day in 4 patients. Treatment responses, survival rates and factors affecting survival were analyzed. Treatment responses were observed in 61% of the patients. Liver cirrhosis (P=0.001) and tumor size (P=0.001) significantly affected the tumor responses. Overall survival at 6, 12 and 24 months was 84.8, 60.0 and 44.6%, respectively. On univariate analysis, liver cirrhosis (P=0.003), Karnofsky performance status (P=0.007), tumor size (P<0.001), portal vein tumor thrombosis (P<0.001) and alpha-fetoprotein level (P=0.003) were shown to significantly affect survival. On multivariate analysis, only thrombosis (P=0.039) and alpha-fetoprotein level (P=0.006) were shown to be factors affecting survival. Three-dimensional conformal radiotherapy with thalidomide seems to be effective in the treatment of advanced hepatocellular carcinoma. (author)

  14. A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. Pt. 2

    International Nuclear Information System (INIS)

    Kido, Hiroshi; Higashi, Takao; Katanuma, Nobuhiko

    1977-01-01

    1) An amplifier of the action of glucocorticoid was purified from Proteus mirabilis as described previously. It was found that it amplified the induction of liver tyrosine aminotransferase by dexamethasone markedly with doses of dexamethasone that caused minimal enzyme induction, but had little effect with doses that caused maximal induction. Thus the amplification may represent a saving of glucocorticoid. The amplification of enzyme activity was brought about by increase in amount of enzyme. 2) The amplification was observed when the amplifier was administered before or with dexamethasone, but not when it was given 2 h after dexamethasone. These results and the finding that actinomycin D inhibited the amplification indicate that the amplifier does not act on the translational level of enzyme induction. 3) It was found that the amplifier increased both incorporation of [ 3 H]dexamethasone into the cytosol and binding of [ 3 H]dexamethasone to cytosol protein and that it decreased decay of the [ 3 H]dexamethasone protein complex. (orig.) [de

  15. Synthesis and evaluation of 4-[F-18]fluoro thalidomide for the in vivo studies of angiogenesis

    International Nuclear Information System (INIS)

    Kim, D. H.; Choi, Y. S.; Jeong, K. H.; Lee, K. H.; Choi, Y.; Kim, B. T.

    2005-01-01

    Thalidomide has been recently rediscovered for its possible utility as an antitumor agent, although it was marketed as a sedative in the 1950s and later found to be a potent teratogen. In this study, therefore, F-18 labeled thalidomide was synthesized and evaluated for the in vivo studies of angiogenesis. 4-[F-18]Fluoro thalidomide ([F-18]1) was prepared by labeling of 4-trimethylammonium thalidomide triflate with TBA[F-18]F in DMSO (90 .deg. C, 10 min) and purified by HPLC. The triflate salt was prepared from 3-fluoro phthalic anhydride in 3 steps. [F-18]1 was incubated with HUVEC cells at 37 .deg. C for 15, 30, 60, and 120 min, respectively. Dynamic PET images of [F-18]1 was obtained in mice implanted with LLC cells. In vitro metabolism study of [F-18]1 was carried out using mouse, rabbit, or human liver microsomes in the presence of NADPH, and the metabolites obtained from the mouse liver microsomal incubation of 1 were analyzed using LC-MS. Radiochemical yield of [F-18]1 was 50-60%, and the specific activity was 42-120 GBq/imol. The HUVEC cell uptake of [F-18]1 increased with time (100% at 15 min and 241% at 120 min). PET images showed that the radioactivity was accumulated in the liver, the kidneys and the bladder of the mice, and brain uptake was shown from 40 min postinjection. However, there was low level of radioactivity uptake in tumor. [F-18]1 was not metabolized by mouse, rabbit, or human liver microsomes but was hydrolyzed significantly at physiological pH. The hydrolyzed product was further analyzed by LC-MS, showing a mass peak corresponding to that of 4-fluoro-N-(o-carboxybenzoyl)glutamic acid imide. This result suggests that [F-18]1 is easily hydrolyzed at physiological pH and thus may not be suitable for the in vivo studies of tumor angiogenesis at least in rodents, although it was reported that the hydrolysis product of thalidomide may be responsible for its angiogenesis activity in humans

  16. Does Dexamethasone Helps in Meningococcal Sepsis?

    OpenAIRE

    Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

    2017-01-01

    Purpose: Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. Methods: In this non-interventional cl...

  17. Resolving a double standard for risk management of thalidomide: an evaluation of two different risk management programmes in Japan.

    Science.gov (United States)

    Ooba, Nobuhiro; Sato, Tsugumichi; Watanabe, Hikaru; Kubota, Kiyoshi

    2010-01-01

    Thalidomide, once withdrawn because of its teratogenicity, has now been re-launched worldwide. In Japan, thalidomide has been imported by individual doctors since around the year 2000. In October 2008, it was approved for the treatment of multiple myeloma (MM) by the Ministry of Health, Labour and Welfare (MHLW) on the condition that the manufacturer implemented a risk management programme termed the Thalidomide Education and Risk Management System (TERMS). It is likely that the imports of thalidomide will be used off-label to treat diseases other than MM. Thus, the MHLW is also planning to introduce a web-based registration system, referred to as the Safety Management System for Unapproved Drugs (SMUD), for thalidomide imported by individual doctors. To evaluate the difference between TERMS and SMUD and establish a way to resolve the 'double standard' for risk management of thalidomide treatment in Japan. The fraction of patients with disorders other than MM was estimated by the volume of annual imports obtained from the MHLW and records of the imports for patients with MM, other oncological diseases (ODs) and non-ODs in 2007 through a major supplier covering 63% of the total imported thalidomide. The information for TERMS was obtained from web pages of the manufacturer and the MHLW. The components of TERMS were compared with those in SMUD. Provided that the distribution of the indication for thalidomide (MM) in 2007, estimated from the records of imports through the major supplier, is representative of the entire nation, it is estimated that on average 866 patients, including 851 (98.3%) with MM, are using thalidomide on any one day. However, if the major supplier's imports, which account for 63% of the total imports, are not representative of the nation as a whole, possibly only half of the patients treated with thalidomide in Japan have MM. This would be the case in a scenario where the remaining 37% of imports are exclusively used to treat disorders other than

  18. Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

    OpenAIRE

    Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

    2013-01-01

    Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. H...

  19. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    DEFF Research Database (Denmark)

    Vangsted, A. J.; Soeby, K.; Klausen, T.W.

    2010-01-01

    . We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion...

  20. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials

    DEFF Research Database (Denmark)

    Fayers, Peter M; Palumbo, Antonio; Hulin, Cyrille

    2011-01-01

    or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS...

  1. Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Tânia R.C. Vergara

    2017-09-01

    Conclusions: Short-term use of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4+ cell count without changes to the CD8+ cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication.

  2. Does Dexamethasone Helps in Meningococcal Sepsis?

    Science.gov (United States)

    Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

    2017-06-01

    Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease.

  3. Intravitreal clindamycin and dexamethasone for toxoplasmic retinochoroiditis.

    Science.gov (United States)

    Kishore, K; Conway, M D; Peyman, G A

    2001-01-01

    To present a new method for the management of toxoplasmic retinochoroiditis (TRC). The patients were females ranging in age from 10 to 61 years (average 26.5). Four eyes of 4 patients were treated with intravitreal injections of 1.0 mg clindamycin in 0.1 mL and 1.0 mg of dexamethasone in 0.1 mL. The injections were given under general or peribulbar anesthesia. Three patients continued one systemic drug. Follow-up ranged from 11 to 26 months (mean 17.5). A favorable response was noted in each eye within two weeks after the intravitreal injections. All patients required 2 to 4 intravitreal injections in the affected eye for the control of TRC. Visual acuity improved in each eye. The disc and macula were preserved in all eyes. Recurrence was noted in one case, which responded to a repeated intravitreal injection of clindamycin and dexamethasone. Intravitreal injections of clindamycin and dexamethasone are well tolerated and may offer an additional strategy to treat TRC in patients who are unable to afford or tolerate systemic therapy, or whose disease progresses despite systemic therapy.

  4. Role of dexamethasone in brachial plexus block

    International Nuclear Information System (INIS)

    Dawood, M.

    2015-01-01

    To evaluate the effect of dexamethasone added to (lignocaine) on the onset and duration of axillary brachial plexus block. Study Design: Randomized controlled trial. Place and Duration of Study: Combined Military Hospital Rawalpindi, from September 2009 to March 2010. Patients and Methods: A total of 100 patients, who were scheduled for elective hand and forearm surgery under axillary brachial plexus block, were randomly allocated to group A in which patients received 40 ml 1.5% lidocaine with 2 ml of isotonic saline (0.9%) and group B in which patients received 40 ml 1.5% lidocaine with 2 ml of dexamethasone (8 mg). Nerve stimulator with insulated needle for multiple stimulations technique was used to locate the brachial plexus nerves. After the injection onset of action and duration of sensory blockade of brachial plexus were recorded at 5 minutes and 15 minutes interval. Results: Group A showed the onset of action of 21.64 ± 2.30 min and in group B it was 15.42 ± 1.44 min (p< 0.001). Duration of nerve block was 115.08 ± 10.92 min in group A and 265.42 ± 16.56 min in group B (p < 0.001). Conclusion: The addition of dexamethasone to 1.5% lignocaine solution in axillary brachial plexus block prolongs the duration of sensory blockade significantly. (author)

  5. Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy

    Directory of Open Access Journals (Sweden)

    A.M. Sales

    2007-02-01

    Full Text Available Type II reaction in leprosy, or erythema nodosum leprosum (ENL, is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients.

  6. A TAD better for myeloma therapy?

    Science.gov (United States)

    Giralt, Sergio

    2010-02-11

    In this issue of Blood, Lokhorst and colleagues report on the results of HOVON-50, a phase 3 randomized trial designed to evaluate the effects of thalidomide during induction treatment and as maintenance in patients with multiple myeloma. There were 556 patients randomly assigned either to 3 cycles of VAD or to TAD. All patients were to receive high-dose melphalan with autologous stem cell support followed by maintenance with interferon for the VAD arm or thalidomide for the TAD arm.(1) This study together with other randomized and nonrandomized trials establish a definitive role for thalidomide as induction therapy in conjunction with dexamethasone, anthracyclines, and alkylating agents.

  7. Glucocorticoid receptors on leukemic cells as evidenced by dexamethasone-induced cytolysis and /sup 3/H-dexamethasone binding

    Energy Technology Data Exchange (ETDEWEB)

    Thraenhardt, H; Haefer, R; Zintl, F

    1987-01-01

    The presence of glucocorticoid receptors on the leukemic cells of 33 patients affected with acute lymphatic leukemia (ALL) and 6 patients affected with acute myeloic leukemia (AML) was investigated by dexamethasone-induced cytolysis and (/sup 3/H)-dexamethasone binding. The tests undertaken proved that after 20 hours of incubation 9 of 26 non-T-non-B-ALL (c-ALL and unclassified ALL) and 2 of AML were lysed with dexamethasone; blood lymphocytes and bone marrow leukocytes of healthy donors, however, were not affected. Non-T-non-B-ALL and AML were able to bind essentially more (/sup 3/H)-dexamethasone than T-ALL. There existed no correlation between dexamethasone binding and dexamethasone-induced cytolysis.

  8. Rituximab and Dexamethasone vs Dexamethasone Monotherapy in Newly Diagnosed Patients with Primary Immune Thrombocytopenia

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Birgens, Henrik Sverre; Frederiksen, Henrik

    2013-01-01

    In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding sy...

  9. Effects of dexamethasone on liver enzymes and some serum ...

    African Journals Online (AJOL)

    Concomitant usage of dexamethasone and other medications may alter electrolyte metabolism and increase the formation of potentially hepatotoxic reactive metabolites which can contribute to elevated liver enzymes. The role of dexamethasone in liver functions and electrolyte metabolism during pregnancy in Yankasa ...

  10. Dexamethasone enhances the anti-emetic effect of metoclopramide ...

    African Journals Online (AJOL)

    Ninety patients, ASA I or II, aged 21-64years were randomly selected to either the dexamethasone-metoclopramide group, metoclopramide group or dexamethasone group using computer-generated random numbers . Spinal anaesthesia was induced in the sitting position under strict aseptic technique with hyperbaric ...

  11. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

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

    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

  12. Oral pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; 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. Six patients responded. Side effects

  13. Dexamethasone-induced haptoglobin release by calf liver parenchymal cells.

    Science.gov (United States)

    Higuchi, H; Katoh, N; Miyamoto, T; Uchida, E; Yuasa, A; Takahashi, K

    1994-08-01

    Parenchymal cells were isolated from the liver of male calves, and monolayer cultures formed were treated with glucocorticoids to examine whether haptoglobin, appearance of which is associated with hepatic lipidosis (fatty liver) in cattle, is induced by steroid hormones. Without addition of dexamethasone, only trace amounts of haptoglobin were detected in culture medium. With addition of dexamethasone (10(-12) to 10(-4) M), considerable amounts of haptoglobin were released into the medium. Maximal release was observed at concentrations of 10(-8) to 10(-6) M dexamethasone. Haptoglobin release was similarly induced by cortisol, although the effect was less potent than that of dexamethasone. Actinomycin D (a known protein synthesis inhibitor) dose-dependently reduced amounts of haptoglobin released in response to 10(-8) M dexamethasone. Dexamethasone also induced annexin I, which is known to be synthesized in response to glucocorticoids. Dexamethasone treatment resulted in reduced protein kinase C activity in the cell cytosol, which has been shown to be an early event in dexamethasone-treated cells. Other than glucocorticoids, estradiol induced haptoglobin release, whereas progesterone was less effective. The association of haptoglobin with hepatic lipidosis can be reasonably explained by the fact that haptoglobin production by the liver is induced by glucocorticoids and estradiol, and these steroid hormones are triggers for development of hepatic lipidosis in cattle.

  14. Evaluation of gabapentin and dexamethasone alone or in combination for pain control after adenotonsillectomy in children

    Directory of Open Access Journals (Sweden)

    Sabry Mohammad Amin

    2014-01-01

    Full Text Available Background: Different methods and many drugs have been used to control the post-operative pain. In this study, we evaluate the role of gabapentin premedication and/or dexamethasone in management of post-operative pain following adenotonsillectomy in children. Materials and Methods: In a double-blind randomized study, 120 children were subjected for adenotonsillectomy classified into three equal groups. Group G: Gabapentin 10 mg/kg was given orally 2 h before induction of anesthesia (Gabapentin syrup 250 mg/5 ml. Group D: Children in this group received placebo pre-operatively and received dexamethasone 0.15 mg/kg intravenously after induction of anesthesia, but before surgery. Group C: Children in this group received combination of oral gabapentin 10 mg/kg 2 h before induction of anesthesia and intra-operative 0.15 mg/kg dexamethasone intravenously. All children underwent general anesthesia. Pain score was assisted post-operatively 2 h, 4 h, 6 h, 8 h, 12 h and 18 h after recovery using face, legs, activity, cry, consolability scale. Results: Pain score in Group C and Group G was significantly less at 4 h, 6 h and 8 h post-operatively than in Group D (P 0.05. The time to first analgesia was longer in the Group C than in Group G and Group D and the time to first analgesia was significantly longer in Group G than in Group D (P < 0.05. The total amount of pethidine was less in Group C and Group G than in Group D (P < 0.05. The incidence of post-operative nausea and vomiting was statically insignificant among all groups and no reported post-operative bleeding. Conclusion: Gabapentin 10 mg/kg premedication combined with intra-operative dexamethasone 0.15 mg/kg prolongs the post-operative analgesia following adenotonsillectomy in children and decreases the amount of pethidine used post-operatively with no reported adverse effects or increase in the incidence of post-operative bleeding.

  15. Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury.

    Science.gov (United States)

    Reis, Fernando Fonseca Dos; Reboredo, Maycon de Moura; Lucinda, Leda Marília Fonseca; Bianchi, Aydra Mendes Almeida; Rabelo, Maria Aparecida Esteves; Fonseca, Lídia Maria Carneiro da; Oliveira, Júlio César Abreu de; Pinheiro, Bruno Valle

    2016-01-01

    To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. Wistar rats were allocated to one of three groups: pre-VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p grupos: administração de dexametasona pré-LPIVM (grupo dexametasona); administração de salina pré-LPIVM (grupo controle); e somente ventilação (grupo sham). A LPIVM foi realizada por ventilação com volume corrente alto. Os animais dos grupos dexametasona e controle foram sacrificados em 0, 4, 24 e 168 h após LPIVM. Analisamos gasometria arterial, edema pulmonar, contagens de células (totais e diferenciais) no lavado broncoalveolar e histologia de tecido pulmonar. Em 0, 4 e 24 h após LPIVM, os escores de lesão pulmonar aguda (LPA) foram maiores no grupo controle que no grupo sham (p grupo dexametasona não foi significativamente diferente daquele observado no grupo sham e foi menor que o observado no grupo controle (p grupos controle e dexametasona, com pico em 4 h após LPIVM (p grupo dexametasona que no grupo controle em 4 e 24 h após LPIVM (p grupo controle. A administração de dexametasona antes de LPIVM atenua os efeitos da lesão em ratos Wistar. Os mecanismos moleculares dessa lesão e o possível papel clínico dos corticosteroides na LPIVM ainda precisam ser elucidados.

  16. Does Dexamethasone Helps in Meningococcal Sepsis?

    Science.gov (United States)

    Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

    2017-01-01

    Purpose: Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. Methods: In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Results: Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. Conclusion: The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease. PMID:28974828

  17. The effect of granisetron dexamethasone combination on postoperative nausea and vomiting in gynecological operations

    Directory of Open Access Journals (Sweden)

    Ziya Kaya

    2010-06-01

    Full Text Available Objectives: Postoperative nausea and vomiting (PONV is one of the most frequent adverse effects of anesthesia. PONV postpones hospital stays and also delays recover and getting better, of the patients. The objective of the current study is to compare efficacy of prophylactic granisetron(40 μ/kg + dexamethasone (4 mg combination against PONV in different anesthesia models.Materials and Methods: 72 patients with an age range of 18-72 years and ASA 1 or 2 were enrolled in the present study. The patients were assigned as group 1 propofol-remifentanil (P-R, group 2 propofol- nitrous oxide (P-N2O, group 3 sevoflurane- nitrous oxide (S-N2O and group 4 sevoflurane-remifentanyl-air (S-R+H. Inductions of the patients in all groups were made with intravenous 2-3 mg/kg propofol, 1μ/kg remifentanil and 0.2 mg/kg cis-atracurium. 4 mg of dexamethasone by bolus and 40 μ/kg of granisetron by infusion were administered to the patients in all groups after induction. During the last 10 minutes of the operation, 1mg/kg tramadol was administered.Postoperative nausea and vomiting, VAS scores, and additional antiemetic needs were recorded during postoperative 48 hours.Results: Postoperative 48 hours follow up revealed that PONV was seen 27%, 16%, 38%, 48% frequencies in (P+R, (P+ N2O, (S+ N2O, (S+R+H groups, respectively.While antiemetic requirement was not observed in (P+ N2O and (S+ N2O groups, the patients in (P+R and (S+R+H groups needed additional antiemetic drugs with a frequency of 5.5% and 11% respectively.Conclusion: Granisetron, dexamethasone combination in different anesthetic models did not reveal significant difference in terms of postoperative nausea, vomiting, and additional antiemetic usage.

  18. The inhibitory effect of dexamethasone on platelet-derived growth factor-induced vascular smooth muscle cell migration through up-regulating PGC-1α expression

    International Nuclear Information System (INIS)

    Xu, Wei; Guo, Ting; Zhang, Yan; Jiang, Xiaohong; Zhang, Yongxian; Zen, Ke; Yu, Bo; Zhang, Chen-Yu

    2011-01-01

    Dexamethasone has been shown to inhibit vascular smooth muscle cell (VSMC) migration, which is required for preventing restenosis. However, the mechanism underlying effect of dexamethasone remains unknown. We have previously demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 alpha (PGC-1α) can inhibit VSMC migration and proliferation. Here, we investigated the role of PGC-1α in dexamethasone-reduced VSMC migration and explored the possible mechanism. We first examined PGC-1α expression in cultured rat aortic VSMCs. The results revealed that incubation of VSMCs with dexamethasone could significantly elevate PGC-1α mRNA expression. In contrast, platelet-derived growth factor (PDGF) decreased PGC-1α expression while stimulating VSMC migration. Mechanistic study showed that suppression of PGC-1α by small interfering RNA strongly abrogated the inhibitory effect of dexamethasone on VSMC migration, whereas overexpression of PGC-1α had the opposite effect. Furthermore, an analysis of MAPK signal pathways showed that dexamethasone inhibited ERK and p38 MAPK phosphorylation in VSMCs. Overexpression of PGC-1α decreased both basal and PDGF-induced p38 MAPK phosphorylation, but it had no effect on ERK phosphorylation. Finally, inhibition of PPARγ activation by a PPARγ antagonist GW9662 abolished the suppressive effects of PGC-1α on p38 MAPK phosphorylation and VSMC migration. These effects of PGC-1α were enhanced by a PPARγ agonist troglitazone. Collectively, our data indicated for the first time that one of the anti-migrated mechanisms of dexamethasone is due to the induction of PGC-1α expression. PGC-1α suppresses PDGF-induced VSMC migration through PPARγ coactivation and, consequently, p38 MAPK inhibition.

  19. Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo.

    Science.gov (United States)

    Vasvari, Gergely P; Dyckhoff, Gerhard; Kashfi, Farzaneh; Lemke, Britt; Lohr, Jennifer; Helmke, Burkhard M; Schirrmacher, Volker; Plinkert, Peter K; Beckhove, Philipp; Herold-Mende, Christel C

    2007-10-15

    Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is evidence that it might be more effective in combination with chemotherapy the exact mechanism of action is unclear. Therefore, we investigated its effect in combination with metronomically applied cisplatin in a xenotransplant mouse model characteristic for advanced head and neck squamous cell carcinomas, its possible synergistic action in vitro, and which tumor-derived factors might be targeted by thalidomide. Although thalidomide alone was ineffective, a combined treatment with low-dose cisplatin inhibited significant tumor growth, proliferation and angiogenesis in vivo as well as migration and tube formation of endothelial cells in vitro. Noteworthy, the latter effect was enhanced after coapplication of cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was also observed suggesting a direct antitumor effect. Although thalidomide alone did not influence cell proliferation, it augmented antiproliferative response after cisplatin application emphasizing the idea of a potentiated effect when both drugs are combined. Furthermore, we could show that antiangiogenic effects of thalidomide are related to tumor-cell derived factors including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and Il-8 some known and with, granulocyte colony stimulating growth factor and granulocyte macrophage colony stimulating growth factor, some new target molecules of thalidomide. Altogether, our findings reveal new insights into thalidomide-mediated antitumor and antiangiogenic effects and its interaction with cytostatic drugs. (c) 2007 Wiley-Liss, Inc.

  20. Ondansetron, granisetron, and dexamethasone compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy : A randomized placebo-controlled study.

    Science.gov (United States)

    Erhan, Yamac; Erhan, Elvan; Aydede, Hasan; Yumus, Okan; Yentur, Alp

    2008-06-01

    Laparoscopic cholecystectomies are associated with an appreciably high rate of postoperative nausea and vomiting (PONV). This study was designed to compare the effectiveness of ondansetron, granisetron, and dexamethasone for the prevention of PONV in patients after laparoscopic cholecystectomy. A total of 80 American Society of Anesthesiologists (ASA) physical class I-II patients scheduled for laparoscopic cholecystectomy were included in this randomized, double blind, placebo-controlled study. All patients received a similar standardized anesthesia and operative treatment. Patients were randomly divided into four groups (n = 20 each). Group 1, consisting of control patients, received 0.9% NaCl; group 2 patients received ondansetron 4 mg i.v.; group 3 patients received granisetron 3 mg i.v.; and group 4 patients received dexamethasone 8 mg i.v., all before the induction of anesthesia. Both nausea and vomiting were assessed during the first 24 h after the procedure. The total incidence of PONV was 75% with placebo, 35% with ondansetron, 30% with granisetron, and 25% with dexamethasone. The incidence of PONV was significantly less frequent in groups receiving antiemetics (p granisetron, and ondansetron were not significant. Prophylactic dexamethasone 8 mg i.v. significantly reduced the incidence of PONV in patients undergoing laparoscopic cholecystectomy. Dexamethasone 8 mg was as effective as ondansetron 4 mg and granisetron 3 mg, and it was more effective than placebo.

  1. Injection dexamethasone in preventing postoperative nausea and vomiting: a comparison with placebo in the patients undergoing laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Kashmiri, Z.U.A.; Sheikh, Z.; Haider, S.

    2006-01-01

    To determine the efficacy of intravenous dexamethasone for preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy (lap-chole) and comparing it with normal saline (placebo). After the approval of the hospital's ethical committee, the study was conducted on 60 patients who were randomly divided into two groups, each group containing 30 patients. All belonged to A.S.A-I and A.S.A-II. Randomization was done by envelope draw method. Injections dexamethasone (8 mg in 2mls) and normal saline ( 2 mls ) were given intravenously to respective groups just before induction of anesthesia. Fisher's exact test was applied to compare proportion of PONV between two groups for the recovery room data, while Chi-square test was applied to compare the proportion of PONV between two groups during first 12 hours and second 12 hours. The p-value was calculated at the level of significance chosen as 0.05. In the recovery room where the patient stayed for one hour 10% of patients in the dexamethasone group in comparison with 33% of the patients in the placebo group experienced PONV (p=0.028). In the ward, during first 12 hours observation period, 27% of the patients in the dexamethasone group in comparison with 43% of the patients in the placebo group experienced PONV (p=0.176). During the second 12 hours observation period, 30% of the patients in the dexamethasone in comparison with 80% of the patients in the placebo group experienced PONV (p<0.001). (author)

  2. Synthesis of dexamethasone-4-14C

    International Nuclear Information System (INIS)

    Rao, P.N.; Cessac, J.W.; Hill, K.A.

    1982-01-01

    The bismethylenedioxy (BMD) derivative of dexamethasone 2 was silylated with trimethylchlorosilane and imidazole in dimethylformamide to give the 11β-trimethylsilyloxy BMD derivative 3. The Δ 1 -double bond in 3 was hydrogenated over 5% palladium on carbon to give the Δ 4 -3-oxo steroid 4. Oxidation of 4 with potassium permanganate-sodium metaperiodate gave the seco-acid 5 which on subsequent treatment with acetic anhydride; sodium acetate and triethylamine gave the enol-lactone 6. The enol-lactone 6 was reacted with 14 C-methylmagnesium iodide to give an adduct 7a which on heating at reflux with lithium 2,6-di-t-butylphenoxide in dioxane gave the Δ 4 -3-oxo derivative 8. Compound 8 was heated at reflux with m-iodylbenzoic acid and diphenyl diselenide in toluene to give the Δsup(1,4)-3-oxo steroid 9. The protecting BMD and silyl groups were removed in a single step by reaction with aqueous trifluoroacetic acid containing 2N hydrochloric acid at room temperature to give dexamethasone-4- 14 C 10. (author)

  3. Thalidomide inhibits UVB-induced mouse keratinocyte apoptosis by both TNF-α-dependent and TNF-α-independent pathways

    NARCIS (Netherlands)

    Lu, K.Q.; Brenneman, S.; Burns Jr., R.; Vink, A.; Gaines, E.; Haake, A.; Gaspari, A.

    2003-01-01

    Background: Thalidomide is an anti-inflammatory pharmacologic agent that has been utilized as a therapy for a number of dermatologic diseases. Its anti-inflammatory properties have been attributed to its ability to antagonize tumor necrosis factor-alfa (TNF-α) production by monocytes. However, its

  4. After thalidomide - do we have the right balance between public health and intellectual property.

    Science.gov (United States)

    Feldschreiber, Peter; Breckenridge, Alasdair

    2015-01-01

    The current European regulatory and consumer protection legal framework is the legacy of Thalidomide. The disaster led to the introduction of systematic biological and clinical data to endorse the safety and efficacy of new medicines. The European Medicines Directive outlined the pre-clinical, clinical data and product information to evaluate an appropriate benefit. Risk profile of new medicines and also allowed innovative companies to extend patent protection and data/marketing exclusivity periods to compensate for the cost for research and development. However in recent years it has become apparent that the costs and time for research and development are becoming increasingly burdensome, particularly for new drugs with recently discovered mechanisms of action for cancers and neurodegenerative disorders. The costs of development and the commercial uncertainty of such products is reducing commercialisation of these medicines. There is now considerable debate in the regulatory community as to how this regulatory burden may be eased by making earlier review of benefit risk and hence earlier access to authorised medicines. The Courts are moving away from the wide definition of medicinal product to a more nuanced view of the biological and clinical therapeutic mechanisms to satisfy the 'functional' limb definition in the Directive. This may be a move away from the rigorous scientific methodology generated after thalidomide. We discuss the ethical and public health implications of this shift in policy and the implications for intellectual property mechanisms currently available to protect the commercial needs of companies.

  5. Does dexamethasone have a perineural mechanism of action?

    DEFF Research Database (Denmark)

    Jæger, P; Grevstad, Jens Ulrik; Koscielniak-Nielsen, Z J

    2016-01-01

    BACKGROUND: Dexamethasone prolongs block duration. Whether this is achieved via a peripheral or a central mechanism of action is unknown. We hypothesized that perineural dexamethasone added as an adjuvant to ropivacaine prolongs block duration compared with ropivacaine alone, by a locally mediated...... effect when controlled for a systemic action. METHODS: We performed a paired, blinded, randomized trial, including healthy men. All subjects received bilateral blocks of the saphenous nerve with ropivacaine 0.5%, 20 ml mixed with dexamethasone 2 mg in one leg and saline in the other, according...

  6. Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling.

    Science.gov (United States)

    Sun, Xiang; Xu, Yang; Wang, Yi; Chen, Qian; Liu, Liu; Bao, Yangyi

    2018-05-15

    BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC. MATERIAL AND METHODS Humanized NSCLC cell lines PC9 and A549 were co-cultured with thalidomide and/or icotinib to test for anti-tumor efficiency. Cell proliferation was measured by MTT assay, cell apoptosis by flow cytometry and cell migration by wound healing assay. Western blot was performed to determine the expression of caspase-3, -8, -9, Bax, EGFR, VEGF-R, AKT, ERK, MMP2, MMP9, and NF-κB. The xenograft mouse model was used to explore the effects of thalidomide and icotinib in vivo. Immunohistochemical testing was used to determine the expression of Ki-67 and TUNEL staining in tumor tissues. RESULTS Treatments of thalidomide and/or icotinib reduced cell viability, induced apoptosis, and suppressed migration. Attenuation of pEGFR and pVEGF-R resulted in deactivation of ERK and AKT pathways, which eventually increased the anti-proliferative response. In PC9 xenograft model, combined administration of thalidomide and icotinib restrained tumor growth with remarkable reduced Ki-67 index and increased TUNEL positive cells. CONCLUSIONS Thalidomide sensitizes icotinib to increase apoptosis and prevent migration, and it may be a potentially promising anti-tumor drug in lung cancer multi-modality therapy.

  7. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

    Science.gov (United States)

    Dimopoulos, Meletios A; Oriol, Albert; Nahi, Hareth; San-Miguel, Jesus; Bahlis, Nizar J; Usmani, Saad Z; Rabin, Neil; Orlowski, Robert Z; Komarnicki, Mieczyslaw; Suzuki, Kenshi; Plesner, Torben; Yoon, Sung-Soo; Ben Yehuda, Dina; Richardson, Paul G; Goldschmidt, Hartmut; Reece, Donna; Lisby, Steen; Khokhar, Nushmia Z; O'Rourke, Lisa; Chiu, Christopher; Qin, Xiang; Guckert, Mary; Ahmadi, Tahamtan; Moreau, Philippe

    2016-10-06

    Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened

  8. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study

    NARCIS (Netherlands)

    Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Vincent, Andrew D.; Korse, Catharina M.; van Klaveren, Rob J.; Schramel, Franz M. N. H.; Pavlakis, Nick; Nowak, Anna K.; Custers, Frank L. J.; Schouwink, J. Hugo; Gans, Steven J. M.; Groen, Harry J. M.; Strankinga, Wim F. M.; Baas, Paul

    2013-01-01

    Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic

  9. 77 FR 32010 - New Animal Drugs; Altrenogest; Dexamethasone; Florfenicol

    Science.gov (United States)

    2012-05-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 516, 520, 522, and 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Altrenogest; Dexamethasone; Florfenicol AGENCY: Food and Drug Administration, HHS. [[Page 32011

  10. Effects of Antenatal Betamethasone and Dexamethasone in Preterm Neonates

    Directory of Open Access Journals (Sweden)

    Chen-Yu Chen

    2005-09-01

    Conclusion: In our study, no significant differences between antenatal betamethasone and dexamethasone were found in complications of preterm neonates. Incomplete courses of antenatal corticosteroids were associated with an increased incidence of RDS compared with complete courses.

  11. Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

    Science.gov (United States)

    Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

    2013-01-01

    Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism. PMID:23365169

  12. Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of β-secretase in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Ping He

    Full Text Available Thalidomide is a tumor necrosis factor alpha (TNFα inhibitor which has been found to have abilities against tumor growth, angiogenesis and inflammation. Recently, it has been applied in clinic for the treatment of multiple myeloma as well as some inflammatory diseases. However, whether thalidomide has any therapeutic effects on neurodegenerative disorders, i.e. Alzheimer's disease (AD is not clear. AD is characterized by excessive amount of amyloid β peptides (Aβ, which results in a significant release of inflammatory factors, including TNFα in the brain. Studies have shown that inhibition of TNFα reduces amyloid-associated pathology, prevents neuron loss and improves cognition. Our recent report showed that genetic inhibition of TNFα/TNF receptor signal transduction down-regulates β amyloid cleavage enzyme 1 (BACE1 activity, reduces Aβ generation and improves learning and memory deficits. However, the mechanism of thalidomide involving in the mitigation of AD neuropathological features remains unclear. Here, we chronically administrated thalidomide on human APPswedish mutation transgenic (APP23 mice from 9 months old (an onset of Aβ deposits and early stage of AD-like changes to 12 months old. We found that, in addition of dramatic decrease in the activation of both astrocytes and microglia, thalidomide significantly reduces Aβ load and plaque formation. Furthermore, we found a significant decrease in BACE1 level and activity with long-term thalidomide application. Interestingly, these findings cannot be observed in the brains of 12-month-old APP23 mice with short-term treatment of thalidomide (3 days. These results suggest that chronic thalidomide administration is an alternative approach for AD prevention and therapeutics.

  13. Talidomida, contextos históricos y éticos Thalidomide, historical and ethical contexts

    Directory of Open Access Journals (Sweden)

    José Ángel Chávez Viamontes

    2009-12-01

    Full Text Available A finales de la década del 50, en Europa, Australia, Japón y varios países africanos, la talidomida provocó más de 10 000 casos de defectos congénitos en hijos de madres que la consumieron durante el embarazo. En 1962, es retirada del mercado. Tres décadas después, se reivindica su prescripción en el manejo de enfermedades de pronóstico desfavorable. Sus propiedades antiangiogénicas e inmunorreguladoras la hacen diferente al fármaco de los años 50 en gran medida. A pesar de poseer las mismas propiedades farmacológicas y riesgos teratogénicos, la molécula talidomida tiene otras las indicaciones, dosis, campos de aplicación y condiciones legales de uso. Esta revisión tiene como objetivo reseñar los contextos históricos y éticos que condicionaron la proscripción de la talidomida a principios de los años 60, así como las actuales condiciones clínicas en que se usan o ensayan actualmente sus efectos terapéuticos.In Europe, Australia, Japan, and some African countries in the late 50's, Thalidomide caused more than 10 000 cases of congenital defects in children whose mothers consumed it during pregnancy. In 1962, it was withdrawn from market. Thirty years later, it is used for the management diseases with unfavorable prognosis. Its antiangiogenic and immunoregulatory characteristics distinguish it from the drug of 1950. Although containing the same pharmacological features and teratogenic risks, the molecule thalidomide does have other prescriptions, doses, application fields, and lawful conditions of use. This revision points out both the historical and ethical contexts, which conditioned the banning of Thalidomide in the early 60's, and the clinical conditions in which its therapeutic effects are used and studied today.

  14. Labor Induction

    Science.gov (United States)

    f AQ FREQUENTLY ASKED QUESTIONS FAQ154 LABOR, DELIVERY, AND POSTPARTUM CARE Labor Induction • What is labor induction? • Why is labor induced? • What is the Bishop score? • What is “ripening ...

  15. Living with thalidomide: health status and quality of life at 40 years.

    Science.gov (United States)

    Bent, N; Tennant, A; Neumann, V; Chamberlain, M A

    2007-06-01

    Thalidomide was first synthesized in 1953 and was subsequently marketed as a mild hypnotic and sedative in more than 20 countries. By 2001 it was estimated that there were 5,000 survivors from the 10,000 - 12,000 babies who were, as a result, born with severe abnormalities. For these survivors, recent concerns have emerged about their physical state, in particular their levels of pain and their ability to maintain independence. It was therefore wished to ascertain health status and current concerns amongst a sample of survivors living in the UK. A combination of qualitative and quantitative methodologies was employed. Qualitative interviews were undertaken with a sample drawn from the population affected by thalidomide known to the Thalidomide Trust. Selection of participants was based upon a theoretical sample frame. Postal questionnaires to examine health status and various psychosocial aspects concerned with living with the consequences of thalidomide were sent subsequently to these same participants and to a random sample of those not originally drawn for the qualitative interviews. For the qualitative interviews, 28 agreed to take part; two refused and the remainder did not respond. Those agreeing to interview were representative of the original compensation bands (Chi-Square = 3.929; p = 0.416). Several themes emerged from these interviews, including the effects on work and career; coping in terms of attitude to life, self-image, confidence, self-esteem, stress and emotion; relationships, independent living issues and emergent problems such as pain, quality of life, and anxiety about the future. A postal questionnaire was then sent to those who had agreed to interview (28), plus a random sample of the remaining group who were not initially chosen for the qualitative interviews. In total 82 people were sent the questionnaire, of whom 41 (50%) responded. Two-thirds of responders were female. Seven out of ten lived with a partner, and over half (56%) had

  16. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    M. Dolenc-Voljč

    2013-11-01

    Full Text Available Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg.

  17. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Science.gov (United States)

    Dolenc-Voljč, M.; Jurčić, V.; Hočevar, A.; Tomšič, M.

    2013-01-01

    Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg) appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg. PMID:24348379

  18. Indeterminate cell histiocytosis in a pediatric patient: successful treatment with thalidomide.

    Science.gov (United States)

    Tóth, Béla; Katona, Mária; Hársing, Judit; Szepesi, Agota; Kárpáti, Sarolta

    2012-04-01

    The 15-year-old male patient presented several 2-6 mm large livid reddish-yellowish, shiny, compact papules on the head, trunk and extremities, which had developed within the last 4 months. Histology showed normal epidermis with dense dermal infiltrate of histiocytes accompanied by few eosinophils, Touton or foamy giant cells. The histiocytes were S100 positive, CD1a negative and did not contain Birbeck granules ultrastructurally. Chest X ray, EEG, skull MRI did not show pathology. Opthalmology, neurology, oto-rhino-laryngology did not reveal alterations. Based upon the clinical symptoms and the histopathology, the diagnosis of indeterminate cell histiocytosis was confirmed. Cryotherapy and cauterization did not stop the progression of the disease, however, under thalidomide treatment no new symptoms developed and the lesions healed with pigmentation.

  19. Antiemetic effects of granisetron versus dexamethasone in clonidine premedicated children undergoing strabismus surgery

    Directory of Open Access Journals (Sweden)

    Indu Sen

    2007-01-01

    Full Text Available In a prospective, double blind, randomized trial, 120 children, aged 3-8 years,ASAI-II, undergoing strabismus repair were randomly divided into three groups (n = 40 each. Oral clonidine premedication (4gg.kg-1 was administered to all the patients two hours prior to surgery. Soon after induction of anaesthesia, Group G patients were administered intravenous granisetron (40gg.kg-1 , Group D intravenous dexamethasone (150gg.kg-1 and group S received 4ml normal saline. Postoperatively, children were continuously monitored and assessed half-hourly till discharge and then after 24 hours for vomiting and pain. The overall incidence of postoperative emesis was lower (15.4% in the Group G compared with the Group D (21.6% in the first 24 hours (P>0.05. The Group S had a highest incidence of postoperative vomiting ((37% P value < 0.0324 compared to group G. The frequency of early vomiting was highest in the S group. Both G and D groups showed better control of delayed emetic episodes. We observed that in children who were premedicated with clonidine, both IV granisetron or dexamethasone were efficacious in reducing the incidence and severity of POV in day-care strabismus surgery.

  20. MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions

    Science.gov (United States)

    BIAN, FANG; WANG, CHANGJUN; TUKLER-HENRIKSSON, JOHANNA; PFLUGFELDER, STEPHEN C.; CAMODECA, CATERINA; NUTI, ELISA; ROSSELLO, ARMANDO; LI, DE-QUAN; DE PAIVA, CINTIA S.

    2016-01-01

    Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix-metalloproteinases (MMPs -1,-3,-9,-13), IL-1β and IL-6, while it significantly increased MMP-8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP-8 induction is responsible for some of the protective effects of Dex in CM, MMP-8 knock out mice (MMP-8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP-8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP-8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL-6, CXCL1, and MMP-1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP-8KO mice. These results suggest that some of the anti-inflammatory effects of Dex are mediated through increased MMP-8 expression. PMID:26923552

  1. Induction linacs

    International Nuclear Information System (INIS)

    Keefe, D.

    1986-07-01

    The principle of linear induction acceleration is described, and examples are given of practical configurations for induction linacs. These examples include the Advanced Technology Accelerator, Long Pulse Induction Linac, Radial Line Accelerator (RADLAC), and Magnetically-Insulated Electron-Focussed Ion Linac. A related concept, the auto accelerator, is described in which the high-current electron-beam technology in the sub-10 MeV region is exploited to produce electron beams at energies perhaps as high as the 100 to 1000 MeV range. Induction linacs for ions are also discussed. The efficiency of induction linear acceleration is analyzed

  2. Effects of dexamethasone on palate mesenchymal cell phospholipase activity

    International Nuclear Information System (INIS)

    Bulleit, R.F.; Zimmerman, E.F.

    1984-01-01

    Corticosteroids will induce cleft palate in mice. One suggested mechanism for this effect is through inhibition of phospholipase activity. This hypothesis was tested by measuring the effects of dexamethasone, a synthetic corticosteroid, on phospholipase activity in cultures of palate mesenchymal cells. Palate mesenchymal cells were prelabeled with [3H]arachidonic acid. The cells were subsequently treated with various concentrations of dexamethasone. Concurrently, cultures of M-MSV-transformed 3T3 cells were prepared identically. After treatment, phospholipase activity was stimulated by the addition of serum or epidermal growth factor (EGF), and radioactivity released into the medium was taken as a measure of phospholipase activity. Dexamethasone (1 X 10(-5) or 1 X 10(-4) M) could inhibit serum-stimulated phospholipase activity in transformed 3T3 cells after 1 to 24 hr of treatment. However, no inhibition of activity was measured in palate mesenchymal cells following this period of treatment. Not until 120 hr of treatment with dexamethasone (1 X 10(-4) M) was any significant inhibition of serum-stimulated phospholipase activity observed in palate mesenchymal cells. When EGF was used to stimulate phospholipase activity, dexamethasone (1 X 10(-5) M) caused an increase in phospholipase activity in palate mesenchymal cells. These observations suggested that phospholipase in transformed 3T3 cells was sensitive to inhibition by dexamethasone. However, palate mesenchymal cell phospholipase is only minimally sensitive to dexamethasone, and in certain instances can be enhanced. These results cannot support the hypothesis that corticosteroids mediate their teratogenic effect via inhibition of phospholipase activity

  3. Dexamethasone minimizes the risk of cranial nerve injury during CEA.

    Science.gov (United States)

    Regina, Guido; Angiletta, Domenico; Impedovo, Giovanni; De Robertis, Giovanni; Fiorella, Marialuisa; Carratu', Maria Rosaria

    2009-01-01

    The incidence of cranial and cervical nerve injury during carotid endarterectomy (CEA) ranges from less than 7.6% to more than 50%. Lesions are mainly due to surgical maneuvers such as traction, compression, tissue electrocoagulation, clamping, and extensive dissections. The use of dexamethasone (DEX) and its beneficial effects in spinal cord injuries have already been described. We investigated whether DEX could also be beneficial to minimize the incidence of cranial and cervical nerve injury during CEA. To evaluate whether dexamethasone is able to reduce the incidence of cranial nerve injuries. From March 1999 through April 2006, 1126 patients undergoing CEA because of high-grade carotid stenosis were enrolled and randomized by predetermined randomization tables into two groups. The first group, "A", included 586 patients that all received an intravenous administration of dexamethasone following a therapeutic scheme. The second group, "B", included 540 control subjects that received the standard pre- and postoperative therapy. All patients were submitted to a deep cervical plexus block, eversion carotid endarterectomy, and selective shunting. Three days after the operation, an independent neurologist and otorhinolaryngologist evaluated the presence of cranial nerve deficits. All patients (group A and group B) showing nerve injuries continued the treatment (8 mg of dexamethasone once in the morning) for 7 days and were re-evaluated after 2 weeks, 30 days, and every 3 months for 1 year. Recovery time took from 2 weeks to 12 months, with a mean time of 3.6 months. The chi(2) test was used to compare the two groups and to check for statistical significance. The incidence of cranial nerve dysfunction was higher in group B and the statistical analysis showed a significant effect of dexamethasone in preventing the neurological damage (P = .0081). The incidence of temporary lesions was lower in group A and the chi(2) test yielded a P value of .006. No statistically

  4. Low-dose dexamethasone during arthroplasty: What do we know about the risks?

    NARCIS (Netherlands)

    Wegener, Jessica T.; Kraal, Tim; Stevens, Markus F.; Hollmann, Markus W.; Kerkhoffs, Gino M. M. J.; Haverkamp, Daniël

    2016-01-01

    Dexamethasone is commonly applied during arthroplasty to control post-operative nausea and vomiting (PONV). However, conflicting views of orthopaedic surgeons and anaesthesiologists regarding the use of dexamethasone raise questions about risks of impaired wound healing and surgical site infections

  5. Randomized clinical trial of dexamethasone versus placebo in laparoscopic inguinal hernia repair

    DEFF Research Database (Denmark)

    Tolver, M A; Strandfelt, P; Bryld, Clara E

    2012-01-01

    The effect of dexamethasone on recovery and length of convalescence has not been evaluated in patients after laparoscopic groin hernia repair. It was hypothesized that preoperative intravenous dexamethasone would reduce postoperative pain.......The effect of dexamethasone on recovery and length of convalescence has not been evaluated in patients after laparoscopic groin hernia repair. It was hypothesized that preoperative intravenous dexamethasone would reduce postoperative pain....

  6. Inductive reasoning.

    Science.gov (United States)

    Hayes, Brett K; Heit, Evan; Swendsen, Haruka

    2010-03-01

    Inductive reasoning entails using existing knowledge or observations to make predictions about novel cases. We review recent findings in research on category-based induction as well as theoretical models of these results, including similarity-based models, connectionist networks, an account based on relevance theory, Bayesian models, and other mathematical models. A number of touchstone empirical phenomena that involve taxonomic similarity are described. We also examine phenomena involving more complex background knowledge about premises and conclusions of inductive arguments and the properties referenced. Earlier models are shown to give a good account of similarity-based phenomena but not knowledge-based phenomena. Recent models that aim to account for both similarity-based and knowledge-based phenomena are reviewed and evaluated. Among the most important new directions in induction research are a focus on induction with uncertain premise categories, the modeling of the relationship between inductive and deductive reasoning, and examination of the neural substrates of induction. A common theme in both the well-established and emerging lines of induction research is the need to develop well-articulated and empirically testable formal models of induction. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  7. Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

    DEFF Research Database (Denmark)

    Thomsen, Karen Louise; Møller, Holger Jon; Graversen, Jonas Heilskov

    2016-01-01

    ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight (421 ± 11 mg vs 465 ± 12 mg, P any other group. CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased...

  8. Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy.

    Directory of Open Access Journals (Sweden)

    Alessia Nicotra

    Full Text Available Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females and 17 controls (37.9±9.0 years; 8 females demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1, L5 radiculopathic sensory impairment (n = 1 and cervical myelopathy (n = 1. In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002 ([95% CI], p-value and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089 in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232 and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169.We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.

  9. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

    Directory of Open Access Journals (Sweden)

    Rubem David Azulay

    2004-10-01

    Full Text Available A talidomida, descoberta na Alemanha Oriental, em 1954, mostrou vários efeitos terapêuticos: antiemético, sedativo e hipnótico. De 1959 a 1961, foram descritas cerca de 12.000 crianças nascidas com defeitos teratogênicos. Seu uso foi, conseqüentemente, suspenso. Sheskin, entretanto, recomeçou a usar a droga e verificou efeito benéfico no eritema nodoso leprótico. A talidomida é derivada do ácido glutâmico. Sua eliminação urinária é mínima (1%. Tem ações: antiinflamatória, imunomoduladora e antiangiogênica. Tem sido usada, com certo êxito terapêutico, em algumas entidades mais adiante estudadas. O principal efeito adverso é teratogênico: alterações nos membros, orelhas, olhos e órgãos internos. Supõe-se que esses efeitos teratogênicos decorram da ação antiangiogênica. Outros efeitos adversos: cefaléia, secura da pele e da mucosa da boca, prurido, erupção cutânea, aumento de peso, hipotireoidismo, neutropenia, bradicardia ou taquicardia e hipotensão. Interage com outros fármacos: barbitúrico, clorpromazina, reserpina, álcool, acetaminofen, histamina, serotonina e prostaglandina.Thalidomide was discovered in East Germany in 1954. It presented with several therapeutic effects: antiemetic, sedative and hypnotic. From 1959 to 1961, roughly 12,000 children born with teratogenic defects were described. Its use was consequently halted. Sheskin started using the drug again and observed its beneficial effect on erythema nodosa leprosum. Thalidomide is derived from glutamic acid. Its urinary elimination is minimal (1%. It has the following actions: anti-inflammatory, immunomodulary and antiangiogenic. It has been used with a successful therapeutic outcome on some entities, which have been studied further. The main side effect is teratogenic: limb alterations, ears, eyes and internal organs. The teratogenic effects are assumed to result from antiangiogenic action. Other side effects are cephalea, dry skin and mouth

  10. Targeting Dexamethasone to Macrophages in a Porcine Endotoxemic Model

    DEFF Research Database (Denmark)

    Granfeldt, Asger; Hvas, Christine Lodberg; Graversen, Jonas Heilskov

    2013-01-01

    -8 minutes. CONCLUSION: Targeted delivery of dexamethasone to macrophages using a humanized CD163 antibody as carrier exhibits anti-inflammatory effects comparable with 50 times higher concentrations of free dexamethasone and does not inhibit endogenous cortisol production. This antibody-drug complex showing......OBJECTIVES: Macrophages are important cells in immunity and the main producers of pro-inflammatory cytokines. The main objective was to evaluate if specific delivery of glucocorticoid to the macrophage receptor CD163 is superior to systemic glucocorticoid therapy in dampening the cytokine response...

  11. Teacher induction

    NARCIS (Netherlands)

    Beijaard, D.; Buitink, J.; Kessels, C.; Peterson, P.; Baker, E.; McGraw, B.

    2010-01-01

    Teacher induction programs are intended to support the professional development of beginning teachers and thereby contribute to the reduction of teacher attrition during the early teaching years. Teacher induction programs are often based upon a deficit model with a focus on the better organization

  12. Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant

    Directory of Open Access Journals (Sweden)

    Yusuf Kale

    2015-08-01

    Full Text Available Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

  13. Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Prosthetic Aspects

    Science.gov (United States)

    Gilpin, R. E.

    1963-01-01

    The types of prostheses available for treatment of congenital amputations in children, and the assistance in habilitation which can be expected from their use, are described in this communication. The limb deformities in children commonly associated with the drug thalidomide are phocomelia and amelia. Prosthetic treatment of these is difficult, but in almost every case some assistance can be offered. The degree of this assistance will depend to a large extent on (1) the number of limbs involved, (2) the site of the deformity, (3) the intellectual capacity of the child. These factors are evaluated by a clinic team, consisting of a prosthetist, a therapist, a social worker, and a doctor, who acts as the clinical chief. They are also embodied into a prescription for a prosthesis and into a program of management. Subsequently, the clinic team also carry out an assessment of the result. The prosthetist makes available his knowledge of present-day appliances, and assures that the way is left open for use of new, and perhaps revolutionary prostheses, in the future. ImagesFig. 1(a)-1(b)Fig. 2Fig. 3Fig. 4 PMID:13947980

  14. Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Surgery of Limb Defects

    Science.gov (United States)

    Hall, John E.

    1963-01-01

    The deformities commonly seen in “thalidomide babies” are described. These vary from relatively uncomplicated radial-ray defects to complete phocomelia of all four extremities. It is suggested that the care of these children is best carried out in a clinic accustomed to dealing with juvenile amputee problems. A plea is made for very early fitting of upper-extremity prostheses (at approximately three months of age) in cases of unilateral upper-limb deficiencies. A “bucket” for sitting should be supplied for children with quadrilateral phocomelia to sit in when they reach seven or eight months of age. Children with severe upper-limb malformations will be candidates for some form of externally powered prostheses. ImagesFig. 1a and 1bFig. 2a and 2bFig. 3a and 3bFig. 4a and 4bFig. 5a, b and cFig. 6a and 6bFig. 7Fig. 8Fig. 9a and 9bFig. 10a,bFig. 10c and d PMID:13952105

  15. Dexamethasone selectively suppresses microglial trophic responses to hippocampal deafferentation

    DEFF Research Database (Denmark)

    Woods, A G; Poulsen, F R; Gall, C M

    1999-01-01

    hippocampus. Daily dexamethasone injections almost completely blocked increases in insulin-like growth factor-1 messenger RNA content, but did not perturb increases in ciliary neurotrophic factor or basic fibroblast growth factor messenger RNA content, in the deafferented dentate gyrus molecular layer...

  16. Effects of Maternal Dexamethasone Exposure During Lactation on ...

    African Journals Online (AJOL)

    olayemitoyin

    examined the effects of lactational dexamethasone exposure on metabolic imbalance and oxidative stress marker in the liver ... control. Basal Fasting Blood Sugar (FBS) was also significantly (p<0.001) higher in the Dex ... Exposure to stress and glucocorticoids hormone ..... Energy expenditure and energy intake during.

  17. The use of dexamethasone in women with preterm premature ...

    African Journals Online (AJOL)

    The use of dexamethasone in women with preterm premature rupture of membranes - A multicentre, double-blind, placebocontrolled, randomised trial. R.C. Pattinson, J.D. Makin, M. Funk, S.D. Delport, A.P. Macdonald, K. Norman, G. Kirsten, C. Stewart, D. Woods, G. Moller, E. Coetzee, P. Smith, J. Anthony, M. Schoon, ...

  18. 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)

    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

  19. 21 CFR 520.540a - Dexamethasone powder.

    Science.gov (United States)

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540a Dexamethasone powder. (a... such as acute arthritic lameness, and for various stress conditions where corticosteroids are required...

  20. Practicing induction:

    DEFF Research Database (Denmark)

    Sprogøe, Jonas; Rohde, Nicolas

    2009-01-01

    We claim that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and organization, what we call a generative dance, ignites both kinds of learning.......We claim that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and organization, what we call a generative dance, ignites both kinds of learning....

  1. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

    Science.gov (United States)

    Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio

    2015-01-08

    Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

  2. Effects of dexamethasone on brain edema. Uptake and distribution of tritiated (/sup 3/H) dexamethasone in cold induced edema

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Motohisa [Okayama Univ. (Japan). School of Medicine

    1982-06-01

    Experimental cerebral edema was produced on the right parietal lobe of Wistar male rats with a cold metal probe cooled by liquid nitrogen. Twenty hour later, /sup 3/H-dexamethasone was either intramuscularly or intravenously injected into rats, estimated in the brain tissue by the liquid scintillation counting method. Edematous brain generally contained much higher /sup 3/H-activity than the control. Furthermore, I.V. injection showed higher /sup 3/H-activity than I.M injection in edematous and control brains at all times. For examination of the subcellular distribution of /sup 3/H-dexamethasone in edematous brain, /sup 3/H-activity was most strongly detected in the supernatant fraction (63%), followed by the heavy mitochondrial fraction (25.4%) and the nuclear fraction (8.4%). Although edematous brain tissue constantly demonstrated higher /sup 3/H-activity than the control, its supernatant fraction conversely had less activity. As a next step, distribution of /sup 3/H-dexamethasone in the supernatant fraction was studies. The result was that the high molecular weight fraction in the edematous brain showed higher radioactivity than the control. From these findings, unequivocal distribution of dexamethasone in the supernatant fraction of edematous brain tissue could be correlated with its biochemical action for preventing brain edema.

  3. Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription*

    Science.gov (United States)

    Hidalgo, Alejandro A.; Deeb, Kristin K.; Pike, J. Wesley; Johnson, Candace S.; Trump, Donald L.

    2011-01-01

    Calcitriol, the active form of vitamin D, in combination with the glucocorticoid dexamethasone (Dex) has been shown to increase the antitumor effects of calcitriol in squamous cell carcinoma. In this study we found that pretreatment with Dex potentiates calcitriol effects by inhibiting cell growth and increasing vitamin D receptor (VDR) and VDR-mediated transcription. Treatment with actinomycin D inhibits Vdr mRNA synthesis, indicating that Dex regulates VDR expression at transcriptional level. Real time PCR shows that treatment with Dex increases Vdr transcripts in a time- and a dose-dependent manner, indicating that Dex directly regulates expression of Vdr. RU486, an inhibitor of glucocorticoids, inhibits Dex-induced Vdr expression. In addition, the silencing of glucocorticoid receptor (GR) abolishes the induction of Vdr by Dex, indicating that Dex increases Vdr transcripts in a GR-dependent manner. A fragment located 5.2 kb upstream of Vdr transcription start site containing two putative glucocorticoid response elements (GREs) was evaluated using a luciferase-based reporter assay. Treatment with 100 nm Dex induces transcription of luciferase driven by the fragment. Deletion of the GRE distal to transcription start site was sufficient to abolish Dex induction of luciferase. Also, chromatin immunoprecipitation reveals recruitment of GR to distal GRE with Dex treatment. We conclude that Dex increases VDR and vitamin D effects by increasing Vdr de novo transcription in a GR-dependent manner. PMID:21868377

  4. Real-time measurement of blood pressure with Nexfin in a patient with thalidomide-related phocomelia.

    Science.gov (United States)

    Earle, Rosie; Vaghadia, Himat; Shanahan, Enda; Tang, Raymond; Sawka, Andrew

    2016-11-01

    We report the novel application of photoplethysmographic technology with the Nexfin HD monitor for real-time measurement of blood pressure (BP) in a patient with tetraamelia. The patient was a 58-year-old man with tetraamelia secondary to thalidomide exposure in utero, who presented for surgical excision of a maxillary schwannoma. Because difficulty of cuff use on rudimentary limbs and failure to gain invasive arterial access due to abnormalities of limb vasculature, this population is known to pose some unique challenges for BP measurement. Nexfin may offer an alternative noninvasive method to detect BP in patients with phocomelia during the perioperative period. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. 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

    Science.gov (United States)

    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; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

    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 dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

  6. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von

  7. Mucosal healing with thalidomide in refractory Crohn's disease patients intolerant of anti-TNF-α drugs: report of 3 cases and literature review.

    Science.gov (United States)

    Scribano, Maria Lia; Cantoro, Laura; Marrollo, Marzia; Cosintino, Rocco; Kohn, Anna

    2014-07-01

    Thalidomide is an oral immunomodulatory and anti-inflammatory drug with antitumor necrosis factor-α (TNF-α) activity. Several case reports and some clinical trials have demonstrated its efficacy in the treatment of refractory Crohn's disease (CD). We report the effect and tolerability of thalidomide in 3 patients with moderate-to-severe CD who were not responsive to anti-TNF-α therapies, and review the relevant literature. The first case is of a 28-year-old female affected by Crohn's colitis complicated by a severe fistulizing perianal disease; she was treated with infliximab, adalimumab, and certolizumab pegol, which were stopped because of intolerance. The second case is of a 39-year-old female with fistulizing ileocolitis complicated by severe arthralgias and perianal disease with loss of response to infliximab and intolerance of certolizumab pegol. The third case is of a 39-year-old male with gastric and ileocolonic CD refractory to immunosuppressors and intolerant of infliximab. All the 3 cases achieved complete clinical remission and endoscopic healing of mucosal lesions at a low dose of thalidomide (50 to 150 mg/d). In our CD patients who experienced loss of response or were unable to tolerate anti-TNF-α drugs, thalidomide was an effective and well-tolerated therapy for inducing and maintaining long-term remission.

  8. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    International Nuclear Information System (INIS)

    Vangsted, Annette J; Rasmussen, Henrik B; Søeby, Karen; Klausen, Tobias W; Abildgaard, Niels; Andersen, Niels F; Gimsing, Peter; Gregersen, Henrik; Vogel, Ulla; Werge, Thomas

    2010-01-01

    The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome

  9. Comparison of Thromboemboli Prophylactic Effect of Aspirin and Low Dose Warfarin in Standard Risk Multiple Myeloma Patients that Treated with Regimens Containing Thalidomide

    Directory of Open Access Journals (Sweden)

    Seyed Amir Dadkhahi

    2017-05-01

    Full Text Available Abstract Background: Most of the current regimens in the treatment of multiple myeloma include thalidomide. Thalidomide is a modulator of the immune system and according to several studies, its main complication is thromboembolism. The aim of this study is to compare the thromboemboli prophylactic effect of aspirin and low dose warfarin in standard risk multiple myeloma patients that treated with regimens containing thalidomide. Materials and Methods: In this double- blind clinical trial study, sixty-six patients with multiple myeloma under treatment with thalidomide-containing regimens with standard risk for thromboembolism who were admitted to Khansari hospital, entered the study according to inclusion and exclusion criteria. The incidence of thromboembolism in these patients was evaluated. Results: Five patients in the warfarin group and 2 patients in the aspirin group had thromboemboli. Chi square analyses showed no significant difference between groups (p=0.635. Conclusion: The results showed that both drugs are effective in preventing thromboembolism and can be used as a prophylactic treatment.

  10. Dexamethasone Intravitreal Implant for Diabetic Macular Edema During Pregnancy

    DEFF Research Database (Denmark)

    Concillado, Michael; Lund-Andersen, Henrik; Mathiesen, Elisabeth R

    2016-01-01

    PURPOSE: To describe the management of diabetic macular edema during pregnancy with the use of a dexamethasone slow-release intravitreal implant. DESIGN: Retrospective, observational, consecutive case series. METHODS: The study included 5 pregnant women who presented with diabetic macular edema...... injection. RESULTS: Diabetic macular edema involving the foveal center was observed between gestational weeks 9 and 23 in 10 eyes of 5 patients. Dexamethasone intravitreal implant injection was given 10 times in 9 eyes with a mean preinjection center field retinal thickness of 535 μm (range, 239-727 μm...... center field thickness and in 6 of 8 eyes by an increase in BCVA of 5 or more approxETDRS letters. A mild transient rise in intraocular pressure occurred in 3 out of 8 eyes. CONCLUSION: Diabetic macular edema involving the foveal center that presented during pregnancy responded promptly to intravitreal...

  11. Induction practice -

    DEFF Research Database (Denmark)

    Rohde, Nicolas; Sprogøe, Jonas

    2007-01-01

    that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and the organization, what we call agenerative dance, ignites both kinds of learning. We focus on and describe the interplay , ignites both kinds...

  12. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis.

    Science.gov (United States)

    Corneli, Howard M; Zorc, Joseph J; Mahajan, Prashant; Majahan, Prashant; Shaw, Kathy N; Holubkov, Richard; Reeves, Scott D; Ruddy, Richard M; Malik, Baqir; Nelson, Kyle A; Bregstein, Joan S; Brown, Kathleen M; Denenberg, Matthew N; Lillis, Kathleen A; Cimpello, Lynn Babcock; Tsung, James W; Borgialli, Dominic A; Baskin, Marc N; Teshome, Getachew; Goldstein, Mitchell A; Monroe, David; Dean, J Michael; Kuppermann, Nathan

    2007-07-26

    Bronchiolitis, the most common infection of the lower respiratory tract in infants, is a leading cause of hospitalization in childhood. Corticosteroids are commonly used to treat bronchiolitis, but evidence of their effectiveness is limited. We conducted a double-blind, randomized trial comparing a single dose of oral dexamethasone (1 mg per kilogram of body weight) with placebo in 600 children (age range, 2 to 12 months) with a first episode of wheezing diagnosed in the emergency department as moderate-to-severe bronchiolitis (defined by a Respiratory Distress Assessment Instrument score > or =6). We enrolled patients at 20 emergency departments during the months of November through April over a 3-year period. The primary outcome was hospital admission after 4 hours of emergency department observation. The secondary outcome was the Respiratory Assessment Change Score (RACS). We also evaluated later outcomes: length of hospital stay, later medical visits or admissions, and adverse events. Baseline characteristics were similar in the two groups. The admission rate was 39.7% for children assigned to dexamethasone, as compared with 41.0% for those assigned to placebo (absolute difference, -1.3%; 95% confidence interval [CI], -9.2 to 6.5). Both groups had respiratory improvement during observation; the mean 4-hour RACS was -5.3 for dexamethasone, as compared with -4.8 for placebo (absolute difference, -0.5; 95% CI, -1.3 to 0.3). Multivariate adjustment did not significantly alter the results, nor were differences detected in later outcomes. In infants with acute moderate-to-severe bronchiolitis who were treated in the emergency department, a single dose of 1 mg of oral dexamethasone per kilogram did not significantly alter the rate of hospital admission, the respiratory status after 4 hours of observation, or later outcomes. (ClinicalTrials.gov number, NCT00119002 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

  13. Effects of thyroxine and dexamethasone on rat submandibular glands

    International Nuclear Information System (INIS)

    Sagulin, G.B.; Roomans, G.M.

    1989-01-01

    Glucocorticoids and thyroxine are known to have a marked effect on the flow rate and protein composition of rat parotid saliva in hormonally intact animals. In the present study, the effects of a one-week treatment of male rats with dexamethasone and thyroxine were studied by electron microscopy and x-ray micro-analysis, and by measurement of the flow rate and determination of the chemical composition of pilocarpine-induced submandibular saliva. Thyroxine had the most extensive effects on the submandibular gland. The acinar cells were enlarged and filled with mucus; the cellular calcium concentration was significantly increased. The flow rate of the submandibular saliva was significantly reduced compared with that in saline-injected control animals. Thyroxine caused an increase in the concentrations of protein, total calcium, and potassium in the saliva. Dexamethasone had no significant effects on gland ultrastructure or on the elemental composition of the acinar cells; flow rate was not affected, but the concentrations of protein, calcium, and potassium were significantly increased. The effects of dexamethasone and thyroxine on the flow rate and protein composition of pilocarpine-induced rat submandibular saliva differ from those reported earlier for rat parotid saliva after simultaneous stimulation with pilocarpine and isoproterenol

  14. Significance of Fractionated Administration of Thalidomide Combined With γ-Ray Irradiation in Terms of Local Tumor Response and Lung Metastasis

    Science.gov (United States)

    Masunaga, Shin-ichiro; Sanada, Yu; Moriwaki, Takahiro; Tano, Keizo; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Watanabe, Tsubasa; Nakagawa, Yosuke; Maruhashi, Akira; Ono, Koji

    2014-01-01

    Background The aim of this study was to evaluate the significance of fractionated administration of thalidomide combined with γ-ray irradiation in terms of local tumor response and lung metastatic potential, referring to the response of intratumor quiescent (Q) cells. Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumor-bearing mice then received γ-ray irradiation after thalidomide treatment through a single or two consecutive daily intraperitoneal administrations up to a total dose of 400 mg/kg in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (= P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results Thalidomide raised the sensitivity of the total cell population more remarkably than Q cells in both single and daily administrations. Daily administration of thalidomide elevated the sensitivity of both the total and Q cell populations, but especially the total cell population, compared with single administration. Daily administration, especially combined with MTH, decreased the number of lung metastases. Conclusion Daily fractionated administration of thalidomide in combination with γ-ray irradiation was thought to be more promising than single administration because of its potential to enhance local tumor response and repress lung metastatic potential. PMID:29147396

  15. Induction Brazing

    DEFF Research Database (Denmark)

    Henningsen, Poul

    , or if the hottest area is located outside the joint interface, a number of defects may appear: the braze metal may flow away from the joint, the flux may burn off, poor binding of the braze metal may appear or the braze metal may be overheated. Joint geometry as well as electro-magnetic properties of the work piece...... presents a combined numerical and experimental method for determination of appropriate/optimiged coil geometry and position in induction brazing tube-to-plate joints of different ratios between tube and plate thickness and different combinations of the materials stainless steel, brass and copper....... The method has proven to give successful results in brazing tube-plate joints of copper-brass, copper-stainless steel, stainless steel-brass, and stainless steel-stainless steel. A new design of an adjustable flux concentrator for induction heating tube-to-plate joints is proposed and tested on a variety...

  16. Induction of dexamethasone (DM) of histidine decarboxylase (HDC) in mast cells

    International Nuclear Information System (INIS)

    Ichikawa, A.; Imanishi, N.; Nakayama, T.; Asano, M.; Tomita, K.

    1986-01-01

    Effects of glucocorticoids on HDC in cultured mouse mastocytoma P-815 cells and rat peritoneal mast cells (RPMC) were investigated to explore the role of steroids in inflammatory tissues. DM (1 nM to 10 μM) significantly elevated the histamine content and HDC activity of P-815 cells (37 0 C, 24 hrs), accompanying with a growth retardation of the cells by about 40%. In contrast to histamine, serotonin levels of P-815 cells were decreased by treatment with DM. However, DM had no significant effects on the activities of various enzymes other than HDC present in granules or membrane of P-815 cells. DM-induced increases of histamine and HDC activity were completely suppressed by the addition of cycloheximide and actinomycin D. P-815 cells were found to have the binding sites for 3 H-DM in the cytosol (Kd=2.2 nM, 450 sites/cell) and in the nuclei (Kd=0.1 nM, 39 sites/nucleus). Purified HDC from P-815 cells was identified to be an isozyme of mast cell type enzyme (MW=110K, pI=5.4). In contrast, the basal histamine level of cultured RPMC was not affected by treatment of DM, which suppressed histamine release activity induced by DNP-ascaris antiserum by 40%-50%. Histamine-depleted RPMC after degranulation partially recovered histamine level by 50%-60% in the presence of DM. These results showed that glucocorticoids specifically stimulated histamine formation with the increased de novo synthesis of HDC in mast cells

  17. A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery.

    LENUS (Irish Health Repository)

    Szarvas, Szilvia

    2012-02-03

    In a prospective, double-blinded, randomized trial, we evaluated the efficacy of IV (a) dexamethasone 8 mg, (b) ondansetron 8 mg, and (c) dexamethasone 8 mg plus ondansetron 4 mg for the prevention of postoperative nausea, vomiting (PONV), and pruritus in 130 (ASA physical status I to III) patients undergoing elective major orthopedic surgery after spinal anesthesia with hyperbaric 0.5% bupivacaine and intrathecal morphine. After spinal anesthesia, patients were randomized to one of three groups. Failure of PONV prophylaxis in the 24-h postoperative period occurred more frequently in patients who received dexamethasone alone (29 of 40; 73%) compared with those who received either ondansetron alone (23 of 47; 49%) (P = 0.02) or dexamethasone plus ondansetron together (19 of 43; 44%)(P = 0.01). There was no difference in the incidence of failure of prophylaxis of pruritus (70%, 72%, and 70% in dexamethasone 8 mg, ondansetron 8 mg, and dexamethasone 8 mg plus ondansetron 4 mg, respectively) (P > 0.1) in the 24-h postoperative period. We conclude that the administration of dexamethasone 8 mg with ondansetron 4 mg has no added benefit compared with ondansetron 8 mg alone in the prophylaxis of PONV and pruritus. IMPLICATIONS: Postoperative nausea and vomiting (PONV) and pruritus are common side effects after spinal opioid administration. In this study, dexamethasone 8 mg plus ondansetron 4 mg was as effective as ondansetron 8 mg. The administration of dexamethasone alone was associated with a frequent incidence of PONV, demonstrating a lack of efficacy. This has important cost implications.

  18. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

    Science.gov (United States)

    Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

    2010-07-01

    Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

  19. Dexamethasone-Mediated Upregulation of Calreticulin Inhibits Primary Human Glioblastoma Dispersal Ex Vivo

    Directory of Open Access Journals (Sweden)

    Mohan Nair

    2018-02-01

    Full Text Available Dispersal of Glioblastoma (GBM renders localized therapy ineffective and is a major cause of recurrence. Previous studies have demonstrated that Dexamethasone (Dex, a drug currently used to treat brain tumor–related edema, can also significantly reduce dispersal of human primary GBM cells from neurospheres. It does so by triggering α5 integrin activity, leading to restoration of fibronectin matrix assembly (FNMA, increased neurosphere cohesion, and reduction of neurosphere dispersal velocity (DV. How Dex specifically activates α5 integrin in these GBM lines is unknown. Several chaperone proteins are known to activate integrins, including calreticulin (CALR. We explore the role of CALR as a potential mediator of Dex-dependent induction of α5 integrin activity in primary human GBM cells. We use CALR knock-down and knock-in strategies to explore the effects on FNMA, aggregate compaction, and dispersal velocity in vitro, as well as dispersal ex vivo on extirpated mouse retina and brain slices. We show that Dex increases CALR expression and that siRNA knockdown suppresses Dex-mediated FNMA. Overexpression of CALR in GBM cells activates FNMA, increases compaction, and decreases DV in vitro and on explants of mouse retina and brain slices. Our results define a novel interaction between Dex, CALR, and FNMA as inhibitors of GBM dispersal.

  20. Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Decourt, Boris; Drumm-Gurnee, Denise; Wilson, Jeffrey; Jacobson, Sandra; Belden, Christine; Sirrel, Sherye; Ahmadi, Michael; Shill, Holly; Powell, Jessica; Walker, Aaron; Gonzales, Amanda; Macias, Mimi; Sabbagh, Marwan N

    2017-01-01

    To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects. This was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests. A total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial. This study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Enantioseparation of thalidomide and its hydroxylated metabolites using capillary electrophoresis with various cyclodextrins and their combinations as chiral buffer additives.

    Science.gov (United States)

    Meyring, M; Chankvetadze, B; Blaschke, G

    1999-09-01

    The separation of thalidomide (TD) and its hydroxylated metabolites including their simultaneous enantioseparation was studied in capillary electrophoresis (CE) using four different randomly substituted charged cyclodextrin (CD) derivatives, the combinations of some of them with each other, and beta-CD. TD, as well as two metabolites recently found in incubations of human liver microsomes and human blood, 5-hydroxythalidomide (5-OH-TD) and one of the diastereomeric 5'-hydroxythalidomides (5'-OH-TD), are neutral compounds. Therefore, they were resolved using charged chiral selectors in CE. Two different separation modes (normal polarity and carrier mode) and two different capillaries (fused-silica and polyacrylamide-coated) were tested. Based on the behavior of the individual CDs, their designed combinations were selected in order to improve the separation selectivity and enantioselectivity. Under optimized conditions all three chiral compounds and their enantiomers were resolved simultaneously.

  2. Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

    NARCIS (Netherlands)

    Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating

  3. Pregabalin and dexamethasone improves post-operative pain treatment after tonsillectomy

    DEFF Research Database (Denmark)

    Mathiesen, O; Jørgensen, D G; Hilsted, K L

    2011-01-01

    Post-tonsillectomy pain can be severe. We investigated the analgesic effect from combinations of paracetamol, pregabalin and dexamethasone in adults undergoing tonsillectomy.......Post-tonsillectomy pain can be severe. We investigated the analgesic effect from combinations of paracetamol, pregabalin and dexamethasone in adults undergoing tonsillectomy....

  4. Effect of dexamethasone in primary intracerebral hemorrhage in the south west of iran

    International Nuclear Information System (INIS)

    Sharafadinzadeh, N.; Baghebanian, S.M.; Pipelzadeh, M.; Moravej, A. A.; Ghanavatiz, P.

    2008-01-01

    Previous study revealed the value of dexamethasone in the treatment of vasogenic edema associated with brain tumor and abscess. However there are poor documented studies about its usefulness in primary intracerebral hemorrhage. In this study we evaluated dexamethasone effects in primary intracerebral hemorrhage. In a double blind randomized placebo-controlled clinical trial we evaluated 200 intracerebral hemorrhage cases between 40 to 80 years old whom were admitted at Golestan Hospital (Ahwaz, IR) between March 2002 and March 2003. They were divided in two groups dexamethasone (N=100) and placebo (N=100). Then mortality, GI bleeding, fever, electrolytes disturbances, hypertension and hyperglycemic status were analyzed in two groups. Ethical considerations were employed and subjects were followed by appropriate statistical methods for 21 days to assess the major outcomes. Mortality was much higher in the dexamethasone group; Dexamethasone group (49.3%) and placebo (23.4%) and also fever was higher seen in the dexamethasone group; dexamethasone group (40.2%) and placebo group (24.7%) but there was not any significant statistical difference between two groups as regards other complications. Dexamethasone is widely used for cerebral edema associated conditions but in this study we saw that it's complications in intracerebral hemorrhage such as increasing fever and mortality are significantly higher. Hence it use for treatment of primary intracerebral hemorrhage should be reconsidered. (author)

  5. Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease

    Science.gov (United States)

    Quinn, Charles T.; Stuart, Marie J.; Kesler, Karen; Ataga, Kenneth I.; Wang, Winfred C.; Styles, Lori; Smith-Whitley, Kim; Wun, Ted; Raj, Ahsok; Hsu, Lewis L.; Krishnan, Suba; Kuypers, Frans A; Setty, B. N. Yamaja; Rhee, Seungshin; Key, Nigel S.; Buchanan, George R.

    2011-01-01

    Summary Tapered oral dexamethasone for acute chest syndrome (ACS) in sickle cell anaemia was studied using a novel ACS assessment tool and investigational biomarkers. Twelve participants were randomized (mean age 17.3 years) before early study termination. Dexamethasone decreased duration of hospitalization for ACS by 20.8 h compared to placebo (P=0.024). Rebound pain occurred in both groups (3 dexamethasone vs. 1 placebo). Overall, dexamethasone decreased the leucocyte activation biomarker, sL-selectin; however, participants with rebound pain had higher sL-selectin within 24 h of treatment (dexamethasone or placebo). This ACS assessment tool was feasibly applied, and sL-selectin is a promising biomarker of ACS therapy. PMID:21848879

  6. Atomoxetine Prevents Dexamethasone-Induced Skeletal Muscle Atrophy in Mice

    Science.gov (United States)

    Jesinkey, Sean R.; Korrapati, Midhun C.; Rasbach, Kyle A.; Beeson, Craig C.

    2014-01-01

    Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. β2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator–activated receptor-γ coactivator-1 α (PGC-1α) isoforms, ATP synthase β, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 β subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1α-4-IGF1–Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1α expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. PMID:25292181

  7. Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents.

    Directory of Open Access Journals (Sweden)

    M Estée Török

    Full Text Available Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown.Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability.545 patients were randomised to receive either dexamethasone (274 patients or placebo (271 patients. 50 patients (9.2% were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07 but five-year survival rates were similar (0.54 versus 0.51, p = 0.51 in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07 but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36. The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7% and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32.Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM.ClinicalTrials.gov NCT01317654.

  8. Mechanisms of dexamethasone-induced disturbed sleep and fatigue in paediatric patients receiving treatment for ALL.

    Science.gov (United States)

    Vallance, Kelly; Liu, Wei; Mandrell, Belinda N; Panetta, John C; Gattuso, Jami S; Hockenberry, Marilyn; Zupanec, Sue; Yang, Lei; Yang, Jie; Hinds, Pamela S

    2010-07-01

    Dexamethasone contributes to high cure rates in paediatric acute lymphoblastic leukaemia (ALL) but significantly and adversely alters sleep and fatigue. Herein we explored three mechanisms (pharmacokinetics, serum albumin and pharmacogenetics) through which dexamethasone may cause debilitating fatigue and disrupted sleep. We enrolled 100 patients on a 10-d study: 5-d of no dexamethasone (OFF DEX) followed by 5-d of dexamethasone (ON DEX) during continuation chemotherapy. Sleep variables were collected with continuous actigraphy on days 1 through 5, both OFF DEX and ON DEX. On days 2 and 5 of each 5-d period, parents and patients 7 years of age and older completed a sleep diary and Fatigue Scale questionnaire. Blood was collected at 0 (pre-dexamethasone), 1, 2, 4 and 8 h after the first oral dexamethasone dose for pharmacokinetic analysis. Serum albumin concentration was retrospectively analysed in stored samples. Patient DNA was genotyped for 99 polymorphic loci in candidate genes associated with glucocorticoid metabolism. Dexamethasone clearance was significantly greater in younger patients than in older ones and in lower risk patients. In multiple regression models, risk group was significantly related to pharmacokinetic parameters. We found that polymorphisms in three genes (AHSG, IL6, POLDIP3) were significantly associated with sleep measures but not with fatigue. Risk group had the most significant relationship with disrupted sleep in patients while on dexamethasone. Serum albumin levels had neither a direct relationship with sleep or fatigue variables nor an indirect relationship through systemic exposure to dexamethasone. We identified candidate genes that may help explain the adverse events of disrupted sleep in paediatric patients receiving dexamethasone. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Biodegradable polyurethane nanocomposites containing dexamethasone for ocular route

    International Nuclear Information System (INIS)

    Rodrigues da Silva, Gisele; Silva-Cunha, Armando da; Behar-Cohen, Francine; Ayres, Eliane; Orefice, Rodrigo L.

    2011-01-01

    The treatment of posterior segment ocular diseases, such as uveitis, by using eye drops and oral drugs is usually not effective due to the body's natural barriers to drug penetration. In this study, ocular implants to treat uveitis were synthesized by incorporating dexamethasone acetate, an important type of corticoid used in the treatment of some uveitis, into a biodegradable polyurethane containi clay nanoparticles. Biodegradable polyurethane nanocomposites having poly(caprolactone) oligomers as soft segments were obtained by delaminating clay particles within a polyurethane aqueous dispersion. The drug was incorporated into the polymer by dispersing it in the waterborne polyurethane followed by a drying step. Nanoparticles derived from clay were demonstrated to be able to tailor the mechanical properties of polyurethanes to achieve values that can match the properties of ocular soft tissues. Infrared spectra (FTIR) showed that the presence of clay particles was able to change the microphase separation process typical of polyurethanes. X-ray diffraction and small angle x-ray scattering (SAXS) results were explored to show that the incorporation of both dexamethasone acetate and nanocomponents derived from clay led to a less defined two-phase polyurethane. The presence of clay nanoparticles increased the rate of drug release measured in vitro. Human retinal pigment epithelial cells (ARPE-19) were cultured in contact with polyurethanes and polyurethane nanocomposites, and the viability of them (evaluated by using MTT assay after 7 days) showed that no toxic components were released from polyurethanes containing no drugs during the test.

  10. Dexamethasone nanowafer as an effective therapy for dry eye disease.

    Science.gov (United States)

    Coursey, Terry G; Henriksson, Johanna Tukler; Marcano, Daniela C; Shin, Crystal S; Isenhart, Lucas C; Ahmed, Faheem; De Paiva, Cintia S; Pflugfelder, Stephen C; Acharya, Ghanashyam

    2015-09-10

    Dry eye disease is a major public health problem that affects millions of people worldwide. It is presently treated with artificial tear and anti-inflammatory eye drops that are generally administered several times a day and may have limited therapeutic efficacy. To improve convenience and efficacy, a dexamethasone (Dex) loaded nanowafer (Dex-NW) has been developed that can release the drug on the ocular surface for a longer duration of time than drops, during which it slowly dissolves. The Dex-NW was fabricated using carboxymethyl cellulose polymer and contains arrays of 500 nm square drug reservoirs filled with Dex. The in vivo efficacy of the Dex-NW was evaluated using an experimental mouse dry eye model. These studies demonstrated that once a day Dex-NW treatment on alternate days during a five-day treatment period was able to restore a healthy ocular surface and corneal barrier function with comparable efficacy to twice a day topically applied dexamethasone eye drop treatment. The Dex-NW was also very effective in down regulating expression of inflammatory cytokines (TNF-α, and IFN-γ), chemokines (CXCL-10 and CCL-5), and MMP-3, that are stimulated by dry eye. Despite less frequent dosing, the Dex-NW has comparable therapeutic efficacy to topically applied Dex eye drops in experimental mouse dry eye model, and these results provide a strong rationale for translation to human clinical trials for dry eye. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Biodegradable polyurethane nanocomposites containing dexamethasone for ocular route

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues da Silva, Gisele [Federal University of Sao Joao Del Rei, School of Pharmacy, Divinopolis, Minas Gerais (Brazil); Silva-Cunha, Armando da [Federal University of Minas Gerais, School of Pharmacy, Belo Horizonte, Minas Gerais (Brazil); Behar-Cohen, Francine [INSERM, Physiopathology of ocular diseases: Therapeutic innovations, Institut des Cordeliers, Paris (France); Laboratoire d' Innovations Therapeutiques, Fondation Rothschild, Paris (France); Universite Rene Descartes, Hotel Dieu University Hospital, Paris (France); Ayres, Eliane [Federal University of Minas Gerais, Department of Metallurgical and Materials Engineering, Belo Horizonte, Minas Gerais (Brazil); Orefice, Rodrigo L., E-mail: rorefice@demet.ufmg.br [Federal University of Minas Gerais, Department of Metallurgical and Materials Engineering, Belo Horizonte, Minas Gerais (Brazil)

    2011-03-12

    The treatment of posterior segment ocular diseases, such as uveitis, by using eye drops and oral drugs is usually not effective due to the body's natural barriers to drug penetration. In this study, ocular implants to treat uveitis were synthesized by incorporating dexamethasone acetate, an important type of corticoid used in the treatment of some uveitis, into a biodegradable polyurethane containi clay nanoparticles. Biodegradable polyurethane nanocomposites having poly(caprolactone) oligomers as soft segments were obtained by delaminating clay particles within a polyurethane aqueous dispersion. The drug was incorporated into the polymer by dispersing it in the waterborne polyurethane followed by a drying step. Nanoparticles derived from clay were demonstrated to be able to tailor the mechanical properties of polyurethanes to achieve values that can match the properties of ocular soft tissues. Infrared spectra (FTIR) showed that the presence of clay particles was able to change the microphase separation process typical of polyurethanes. X-ray diffraction and small angle x-ray scattering (SAXS) results were explored to show that the incorporation of both dexamethasone acetate and nanocomponents derived from clay led to a less defined two-phase polyurethane. The presence of clay nanoparticles increased the rate of drug release measured in vitro. Human retinal pigment epithelial cells (ARPE-19) were cultured in contact with polyurethanes and polyurethane nanocomposites, and the viability of them (evaluated by using MTT assay after 7 days) showed that no toxic components were released from polyurethanes containing no drugs during the test.

  12. Intravenous Dexamethasone Pulse Therapy For Extensive Alopecia Areata

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    1999-01-01

    Full Text Available Patient with extensive alopecia areata (>30% scalp involvement were given 32mg of dexamethasone in 200 ml of 5% dextrose intravenously on three consecutive days (total 96mg every four weeks. Response was quantified as 1 to 25%, 25% to 50%, 50 to 75% and 75 to 100% of terminal hair growth by mapping and serial photographs. They were examined monthly for side effects of steroids. Six patients (5 male and 1 female with a mean age of 32 years were recruited. They had alopecia areata for a period ranging from 3 months to 2.5 years. All the six cases did not show further worsening of alopecia after 3 pulses. However, two of them showed less than 25% hair growth after 4 pulses and did not turn up for follow up. In 2 cases, 25 to 50% growth was observed an 50 to 75% growth was seen in 2 patients (one of them with ophiasic pattern after 6 pulses. The results were cosmetically acceptable for three of them. No adverse effect to steroids was encountered and the patients are still under follow up. The preliminary results show that dexamethasone pulse therapy is safe and effective for extensive alopecia areata.

  13. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary hemorrhagic telangiectasia: results of a prospective phase II clinical trial

    Science.gov (United States)

    Invernizzi, Rosangela; Quaglia, Federica; Klersy, Caherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L

    2016-01-01

    Summary Background Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anemia. Multiple therapeutic approaches have been tried, but they are largely palliative with variable results.We aimed to assess the efficacy of thalidomide in reducing epistaxis in patients with HHT refractory to standard therapy. Methods HHT patients with severe recurrent epistaxis refractory to mini-invasive surgical procedures were included in an open label, phase II, prospective, non-randomized, single-centre study. Thalidomide was administered at a starting dose of 50 mg/day orally. In the event of no response, thalidomide dosage was increased by 50 mg/day every four weeks until response to a maximum dose of 200 mg/day. After response achievement, patients were treated for eight to16 additional weeks. Monthly follow-up was based on the epistaxis severity score and transfusion need, with adverse events being reported (ClinicalTrials.gov Identifier: NCT01485224). Findings Thirty-one patients, mean age 62∙6 (SD 11∙1) years, were enrolled (median follow-up 15∙9 months, 25th-75th 10∙1-22∙3). Treatment induced cessation of bleeding in three cases (9∙7%) and a significant decrease in all epistaxis parameters in 28 cases (90∙3%). Twenty-five patients (80∙7%) obtained remission with 50 mg/day of thalidomide, five (16∙1%) with 100 mg/day and one (3∙2%) with 150 mg/day. Treatment significantly increased hemoglobin levels (pepistaxis in HHT patients, allowing for a rapid, often durable clinical improvement. Funding Telethon Foundation PMID:26686256

  14. Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.

    Science.gov (United States)

    García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia

    2017-12-01

    Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Endocrinologic and psychological effects of short-term dexamethasone in anorexia nervosa.

    Science.gov (United States)

    Gordon, C M; Emans, S J; DuRant, R H; Mantzoros, C; Grace, E; Harper, G P; Majzoub, J A

    2000-09-01

    Patients with anorexia nervosa (AN) have hyperactivity of their hypothalamic-pituitary-adrenal (HPA) axis, sometimes accompanied by elevations of cortisol. We examined whether the normal effects of short-term dexamethasone treatment upon HPA axis suppression and appetite stimulation are observed in these patients. Five young women with AN and ten healthy female controls received one week of high-dose oral dexamethasone (2 mg/m2/d) preceded and followed by hormonal evaluation of sensitivity to glucocorticoids and psychological assessments. No differences in hormone levels of the HPA axis were observed between the two groups and control groups at baseline, after dexamethasone suppression, or following ACTH stimulation testing. However, fasting insulin levels were significantly lower in the AN group, both before and after dexamethasone therapy and their serum leptin levels were also significantly lower. The AN group had significantly lower scores on the Anorexia Nervosa Subtest and the Beck Depression Inventory after dexamethasone compared to controls. On daily analog scales, AN patients had higher anxiety scores while on dexamethasone. Normal sensitivity to glucocorticoids was observed in all parameters examined except for mild abnormalities in pancreatic beta-cell function. These data suggest that AN may represent a state of partial glucocorticoid resistance, as in other states of restricted food intake. Furthermore, these pilot data, including the effects of dexamethasone upon psychological outlook in AN, suggest that glucocorticoids are not an effective therapy for these patients.

  16. Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity.

    Science.gov (United States)

    Topdag, M; Iseri, M; Gelenli, E; Yardimoglu, M; Yazir, Y; Ulubil, S A; Topdag, D O; Ustundag, E

    2012-11-01

    This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals. This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats. Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05). Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

  17. A practical dexamethasone suppression test to evaluate hirsute women

    International Nuclear Information System (INIS)

    Wu, C.H.

    1982-01-01

    Fifty-five hirsute women were subjected to a 2-week dexamethasone (DXM) suppression test. The pre- and post-DXM plasma dehydroepiandrosteronesulfate (DS) and testosterone (T) were measured by radioimmunoassay to define the source of androgen excess in hirsute women. Four patients (7%) failed to have adequate adrenal suppression due to failure in medication. Among the 51 patients with adequate adrenal suppression, the source of androgen excess was clearly defined in 48 patients (94%). Seventeen patients (33%) showed ovarian source, 13 patients (26%) had adrenal source, while 18 patients (35%) revealed a mixed adrenal and ovarian source. Normal baseline DS and T levels were noted in 22% of hirsute women and more than half (55%) of them had ovarian androgen excess. Even in 17 patients with normal DS and elevated T, 6 patients (36%) suggested adrenal androgen excess. The source of androgen excess in hirsute women seems evenly distributed among the ovarian, the adrenal, and the mixed group. (author)

  18. Effect of 8-bromo-cAMP and dexamethasone on glutamate metabolism in rat astrocytes

    International Nuclear Information System (INIS)

    Zielke, H.R.; Tildon, J.T.; Landry, M.E.; Max, S.R.

    1990-01-01

    Glutamine synthetase (GS) activity in cultured rat astrocytes was measured in extracts and compared to the intracellular rate of glutamine synthesis by intact control astrocytes or astrocytes exposed to 1 mM 8-bromo-cAMP (8Br-cAMP) + 1 microM dexamethasone (DEX) for 4 days. GS activity in extracts of astrocytes treated with 8Br-cAMP + DEX was 7.5 times greater than the activity in extracts of control astrocytes. In contrast, the intracellular rate of glutamine synthesis by intact cells increased only 2-fold, suggesting that additional intracellular effectors regulate the expression of GS activity inside the intact cell. The rate of glutamine synthesis by astrocytes was 4.3 times greater in MEM than in HEPES buffered Hank's salts. Synthesis of glutamine by intact astrocytes cultured in MEM was independent of the external glutamine or ammonia concentrations but was increased by higher extracellular glutamate concentrations. In studies with intact astrocytes 80% of the original [U- 14 C]glutamate was recovered in the medium as radioactive glutamine, 2-3% as aspartate, and 7% as glutamate after 2 hours for both control and treated astrocytes. The results suggest: (1) astrocytes are highly efficient in the conversion of glutamate to glutamine; (2) induction of GS activity increases the rate of glutamate conversion to glutamine by astrocytes and the rate of glutamine release into the medium; (3) endogenous intracellular regulators of GS activity control the flux of glutamate through this enzymatic reaction; and (4) the composition of the medium alters the rate of glutamine synthesis from external glutamate

  19. The role of growth retardation in lasting effects of neonatal dexamethasone treatment on hippocampal synaptic function.

    Directory of Open Access Journals (Sweden)

    Yu-Chen Wang

    Full Text Available BACKGROUND: Dexamethasone (DEX, a synthetic glucocorticoid, is commonly used to prevent or lessen the morbidity of chronic lung disease in preterm infants. However, evidence is now increasing that this clinical practice negatively affects somatic growth and may result in long-lasting neurodevelopmental deficits. We therefore hypothesized that supporting normal somatic growth may overcome the lasting adverse effects of neonatal DEX treatment on hippocampal function. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we developed a rat model using a schedule of tapering doses of DEX similar to that used in premature infants and examined whether the lasting influence of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance are correlated with the deficits in somatic growth. We confirmed that neonatal DEX treatment switched the direction of synaptic plasticity in hippocampal CA1 region, favoring low-frequency stimulation- and group I metabotropic glutamate receptor agonist (S-3,5,-dihydroxyphenylglycine-induced long-term depression (LTD, and opposing the induction of long-term potentiation (LTP by high-frequency stimulation in the adolescent period. The effects of DEX on LTP and LTD were correlated with an increase in the autophosphorylation of Ca(2+/calmodulin-dependent protein kinase II at threonine-286 and a decrease in the protein phosphatase 1 expression. Neonatal DEX treatment resulted in a disruption of memory retention subjected to object recognition task and passive avoidance learning. The adverse effects of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance of the animals from litters culled to 4 pups were significantly less than those for the 8-pup litters. However, there was no significant difference in maternal care between groups. CONCLUSION/SIGNIFICANCE: Our results demonstrate that growth retardation plays a crucial role in DEX-induced long-lasting influence of

  20. Transcriptional profiling of mesenchymal stromal cells from young and old rats in response to Dexamethasone

    Directory of Open Access Journals (Sweden)

    Rechavi Gideon

    2006-04-01

    Full Text Available Abstract Background Marrow-derived stromal cells (MSCs maintain the capability of self-renewal and differentiation into multiple lineages in adult life. Age-related changes are recognized by a decline in the stemness potential that result in reduced regeneration potential of the skeleton. To explore the molecular events that underline skeletal physiology during aging we catalogued the profile of gene expression in ex vivo cultured MSCs derived from 3 and 15 month old rats. The ex vivo cultured cells were analyzed following challenge with or without Dexamethasone (Dex. RNA retrieved from these cells was analyzed using Affymetrix Gene Chips to compare the effect of Dex on gene expression in both age groups. Results The molecular mechanisms that underline skeletal senescence were studied by gene expression analysis of RNA harvested from MSCs. The analysis resulted in complex profiles of gene expression of various differentiation pathways. We revealed changes of lineage-specific gene expression; in general the pattern of expression included repression of proliferation and induction of differentiation. The functional analysis of genes clustered were related to major pathways; an increase in bone remodeling, osteogenesis and muscle formation, coupled with a decrease in adipogenesis. We demonstrated a Dex-related decrease in immune response and in genes that regulate bone resorption and an increase in osteoblastic differentiation. Myogenic-related genes and genes that regulate cell cycle were induced by Dex. While Dex repressed genes related to adipogenesis and catabolism, this decrease was complementary to an increase in expression of genes related to osteogenesis. Conclusion This study summarizes the genes expressed in the ex vivo cultured mesenchymal cells and their response to Dex. Functional clustering highlights the complexity of gene expression in MSCs and will advance the understanding of major pathways that trigger the natural changes

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    on acute and sustained pain after lumbar disk surgery. In this blinded study, 160 patients undergoing lumbar disk surgery were randomly assigned to 16 mg IV dexamethasone or placebo. All patients received perioperative paracetamol and ibuprofen, and postoperative IV patient-controlled analgesia...... months postoperatively. Acute pain during mobilization (weighted average area under the curve, 2-24 hours) was significantly reduced in the dexamethasone group: 33 (22) mm vs placebo 43 (18) mm, (95% confidence interval [CI] 3-16) P = 0.005. Vomiting 0 to 24 hours postoperatively was reduced....../paralysis of the legs in the dexamethasone and placebo groups, respectively, 3 months postoperatively (P = 0.20). In conclusion, preoperative dexamethasone significantly reduced pain during mobilization and vomiting, after lumbar disk surgery. No significant effects were observed 3 months postoperatively....

  2. Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Warris, Lidewij T.; van den Akker, Erica L. T.; Aarsen, Femke K.; Bierings, Marc B.; van den Bos, Cor; Tissing, Wim J. E.; Sassen, Sebastiaan D. T.; Veening, Margreet A.; Zwaan, Christian M.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied

  3. Dexamethasone prolongs local analgesia after subcutaneous infiltration of bupivacaine microcapsules in human volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Werner, Mads U; Lacouture, Peter G

    2002-01-01

    BACKGROUND: The addition of small amounts of dexamethasone to extended-release formulations of bupivacaine in microcapsules has been found to prolong local analgesia in experimental studies, but no clinical data are available. METHODS: In a double-blinded study, 12 healthy male volunteers were...... randomized to receive simultaneous subcutaneous injections of bupivacaine microcapsules with dexamethasone and bupivacaine microcapsules without dexamethasone in each calf. Local analgesia was assessed with a validated human pain model; main parameters evaluated were thermal, mechanical, and pain detection...... curve [AUC]) were considered best estimate of analgesia. Safety evaluations were performed daily for the first week and at 2 weeks, 6 weeks, and 6 months after injection. RESULTS: The addition of dexamethasone significantly prolonged local analgesia of bupivacaine microcapsules without influence...

  4. Subdural infusion of dexamethasone inhibits leukomyelitis after acute spinal cord injury in a rat model

    Czech Academy of Sciences Publication Activity Database

    Kwiecien, J. M.; Jarocz, B.; Urdzíková, Lucia; Rola, R.; Dabrowski, W.

    2015-01-01

    Roč. 53, č. 1 (2015), s. 41-51 ISSN 1641-4640 Institutional support: RVO:68378041 Keywords : spinal cord injury * leukomyelitis * macrophage s * subdural infusion * dexamethasone Subject RIV: FH - Neurology Impact factor: 1.233, year: 2015

  5. Dexamethasone-suppressed cortisol awakening response predicts treatment outcome in posttraumatic stress disorder

    NARCIS (Netherlands)

    Nijdam, M. J.; van Amsterdam, J. G. C.; Gersons, B. P. R.; Olff, M.

    2015-01-01

    Posttraumatic stress disorder (PTSD) has been associated with several alterations in the neuroendocrine system, including enhanced cortisol suppression in response to the dexamethasone suppression test. The aim of this study was to examine whether specific biomarkers of PTSD predict treatment

  6. β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy.

    Science.gov (United States)

    Aversa, Zaira; Alamdari, Nima; Castillero, Estibaliz; Muscaritoli, Maurizio; Rossi Fanelli, Filippo; Hasselgren, Per-Olof

    2012-07-13

    High levels of glucocorticoids result in muscle wasting and weakness. β-hydroxy-β-methylbutyrate (HMB) attenuates the loss of muscle mass in various catabolic conditions but the influence of HMB on glucocorticoid-induced muscle atrophy is not known. We tested the hypothesis that HMB prevents dexamethasone-induced atrophy in cultured myotubes. Treatment of cultured L6 myotubes with dexamethasone resulted in increased protein degradation and expression of atrogin-1 and MuRF1, decreased protein synthesis and reduced myotube size. All of these effects of dexamethasone were attenuated by HMB. Additional experiments provided evidence that the inhibitory effects of HMB on dexamethasone-induced increase in protein degradation and decrease in protein synthesis were regulated by p38/MAPK- and PI3K/Akt-dependent cell signaling, respectively. The present results suggest that glucocorticoid-induced muscle wasting can be prevented by HMB. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Effects of adding dexamethasone or ketamine to bupivacaine for ultrasound-guided thoracic paravertebral block in patients undergoing modified radical mastectomy: A prospective randomized controlled study

    Directory of Open Access Journals (Sweden)

    Mona Blough El Mourad

    2018-01-01

    Full Text Available Background and Aims: Pain after modified radical mastectomy (MRM has been successfully managed with thoracic paravertebral block (TPVB. The purpose of this study was to evaluate the effect of adding dexamethasone or ketamine as adjuncts to bupivacaine in TPVB on the quality of postoperative analgesia in participants undergoing MRM. Methods: This prospective randomised controlled study enrolled ninety adult females scheduled for MRM. Patients were randomised into three groups (30 each to receive ultrasound-guided TPVB before induction of general anaesthesia. Group B received bupivacaine 0.5% + 1 ml normal saline, Group D received bupivacaine 0.5% + 1 ml dexamethasone (4 mg and Group K received bupivacaine 0.5% + 1 ml ketamine (50 mg. Patients were observed for 24 h postoperatively to record time to first analgesic demand as a primary outcome, pain scores, total rescue morphine consumption and incidence of complications. Results: Group K had significantly longer time to first analgesic demand than group D and control group (18.0 ± 6.0, 10.3 ± 4.5 and 5.3 ± 3.1 hours respectively; P = 0.0001. VAS scores were significantly lower in group D and group K compared to control group at 6h and 12 h postoperative (p 0.0001 and 0.0001 respectively while group K had lower VAS at 18 hours compared to other two groups (P = 0.0001. Control group showed the highest mean 24 h opioid consumption (8.9 ± 7.9 mg compared to group D and group K (3.60 ± 6.92 and 2.63 ± 5.24 mg, P = 0.008,0.001 respectively. No serious adverse events were observed. Conclusion: Ketamine 50 mg or dexamethasone 4 mg added to bupivacaine 0.5% in TPVB for MRM prolonged the time to first analgesic request with no serious side effects.

  8. Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation.

    LENUS (Irish Health Repository)

    Butler, Joseph S

    2010-09-01

    The Wnt\\/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in bone development and remodeling. The objectives of this study were firstly, to determine the effects of dexamethasone exposure on Wnt\\/β-catenin signaling at an intracellular and transcriptional level, and secondly, to assess the phenotypic effects of silencing the Wnt antagonist, Dickkopf-1 (Dkk1) in the setting of dexamethasone exposure.

  9. Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D

    2017-08-01

    Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017

  10. Longstanding refractory pseudophakic cystoid macular edema resolved using intravitreal 0.7 mg dexamethasone implants

    DEFF Research Database (Denmark)

    Brynskov, Troels; Laugesen, Caroline Schmidt; Halborg, Jakob

    2013-01-01

    Refractory pseudophakic cystoid macular edema (PCME) following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition.......Refractory pseudophakic cystoid macular edema (PCME) following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition....

  11. Randomized clinical trial of preoperative dexamethasone on postoperative nausea and vomiting after laparoscopy for suspected appendicitis

    DEFF Research Database (Denmark)

    Kleif, J.; Kirkegaard, A.; Vilandt, J.

    2017-01-01

    Background: Few studies have investigated the effects of preoperative dexamethasone in acute surgical patients. This study examined the effects of 8 mg dexamethasone administered intravenously 30 min before surgery for suspected acute appendicitis. Methods: A multicentre, parallel-group, double......-blind, placebo-controlled study was conducted at two university hospitals in Denmark. Adults undergoing laparoscopic surgery for suspected appendicitis were eligible for inclusion. Participants, healthcare staff and investigators were blinded until all data analysis had been done. The primary outcome...

  12. ¿Por qué se está usando otra vez la talidomida? Why is thalidomide back?

    Directory of Open Access Journals (Sweden)

    Emilio Sanín Pérez

    2004-02-01

    óxica ni en la Enfermedad crónica injerto contra huésped. Background: in 1998 the FDA approved the restricted commercialization of Thalidomide for the treatment of Erithema Nodosum Leprosum. Brazil and Mexico have also regulated its use. Because of the current use of this teratogenic drug in rheumatological, dermatological, infectious and neoplasic diseases, it is necessary to instruct General Practitioners and specialists on its most relevant topics, active principle, benefic and deleterious effects. We carried out a revision by reading and analyzing controlled clinical trials, randomized or not, case series and reviews about thalidomide and its potential uses, that appeared in Medline from January 1993 to December 2003, to draw indications and contraindications in light of the evidence found in them. Results: forty six randomized controlled studies were found and 22 (with at least 50 patients described were reviewed (complete articles and/or including design and end points measured – expressed abstracts, plus 10 reviews and 22 cases series. The analysis allowed us to inform potential or restricted and not indicated uses of thalidomide in humans, its pharmacokynetic principles which explain its benefic and deleterious effects, and recommendations to prevent teratogenesis. Conclusion: thalidomide is available, with restrictions, for the treatment of Erithema Nodosum Leprosum (first line and Multiple Myeloma (refractory to multiple chemotherapy. It appears to have beneficial effects in many other serious conditions refractory to first line treatments: AIDS, esophagus and prostate cancer and some severe dermatosis, rheumatological or not.

  13. Prolonged Suppression of Neuropathic Pain by Sequential Delivery of Lidocaine and Thalidomide Drugs Using PEGylated Graphene Oxide.

    Science.gov (United States)

    Song, Tieying; Gu, Kunfeng; Wang, Wenli; Wang, Hong; Yang, Yunliang; Yang, Lijun; Ma, Pengxu; Ma, Xiaojing; Zhao, Jianhui; Yan, Ruyu; Guan, Jiao; Wang, Chunping; Qi, Yan; Ya, Jian

    2015-11-01

    The management of patients with neuropathic pain is challenging. Monotherapy with a single pain relief drug may encounter different difficulties, such as short duration of efficacy and hence too many times of drug administration, and inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have been proved to provide promising strategies for efficient drug loading, delivery, and release. In the present study, we developed poly(ethylene glycol) methyl ether functionalized graphene oxide (GO) bearing two commonly used drugs of lidocaine (LDC) and thalidomide (THD) as an agent for the treatment of neuropathic pain. The sequential drug release of LDC and THD from the developed LDC-THD-GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro and in vivo, as evidenced by the increased pain threshold in mechanical allodynia and hyperalgesic response tests, and the improved inhibition of proinflammatory cytokines TNF-α, IL-1β, IL-6, and nitric oxide. We believed that the present study herein would hold promise for future development of a new generation of potent agents for neuropathic pain relief. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Outcome with lenalidomide plus dexamethasone followed by early autologous stem cell transplantation in patients with newly diagnosed multiple myeloma on the ECOG-ACRIN E4A03 randomized clinical trial: long-term follow-up.

    Science.gov (United States)

    Biran, N; Jacobus, S; Vesole, D H; Callander, N S; Fonseca, R; Williams, M E; Abonour, R; Katz, M S; Rajkumar, S V; Greipp, P R; Siegel, D S

    2016-09-02

    In Eastern Cooperative Oncology Group-ACRIN E4A03, on completion of four cycles of therapy, newly diagnosed multiple myeloma patients had the option of proceeding to autologous peripheral blood stem cell transplant (ASCT) or continuing on their assigned therapy lenalidomide plus low-dose dexamethasone (Ld) or lenalidomide plus high-dose dexamethasone (LD). This landmark analysis compared the outcome of 431 patients surviving their first four cycles of therapy pursuing early ASCT to those continuing on their assigned therapy. Survival distributions were estimated using the Kaplan-Meier method and compared with log-rank test. Ninety patients (21%) opted for early ASCT. The 1-, 2-, 3-, 4- and 5-year survival probability estimates were higher for early ASCT versus no early ASCT at 99, 93, 91, 85 and 80% versus 94, 84, 75, 65 and 57%, respectively. The median overall survival (OS) in the early versus no early ASCT group was not reached (NR) versus 5.78 years. In patients 50, 0.25). In patients ⩾65 years of age, median OS in the early versus no early ASCT was NR versus 5.11 years. ASCT dropped out of statistical significance (P=0.080). Patients opting for ASCT after induction Ld/LD had a higher survival probability and improvement in OS regardless of dexamethasone dose density.

  15. Dexamethasone and Long-Term Outcome of Tuberculous Meningitis in Vietnamese Adults and Adolescents

    Science.gov (United States)

    Török, M. Estée; Bang, Nguyen Duc; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Thwaites, Guy E.; Thi Quy, Hoang; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Thi Thanh Hoang, Hoang; Wolbers, Marcel; Farrar, Jeremy J.

    2011-01-01

    Background Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown. Methods Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability. Results 545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32). Conclusions Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM. Trial Registration ClinicalTrials.gov NCT01317654 NCT01317654?term = tuberculous+meningitis&rank = 3 PMID:22174748

  16. Single Dexamethasone Intravitreal Implant in the Treatment of Noninfectious Uveitis.

    Science.gov (United States)

    Frère, Ariane; Caspers, Laure; Makhoul, Dorine; Judice, Lia; Postelmans, Laurence; Janssens, Xavier; Lefebvre, Pierre; Mélot, Christian; Willermain, François

    2017-05-01

    To investigate the effect of a single intravitreal dexamethasone implant (IVT-DI; Ozurdex; Allergan, Inc.) on visual acuity, macular thickness, and intraocular pressure (IOP) in active noninfectious uveitis. Medical records of patients with noninfectious active uveitis treated by IVT-DIs were retrospectively reviewed. Uveitis etiologies, treatment indications, best corrected visual acuity (BCVA), central retinal thickness measured by ocular coherence tomography, IOP, and systemic, local, and topical treatments were collected. Parameters were analyzed before the injection of the implant, after 1.5 ± 0.8 months and 4.4 ± 0.9 months for the BCVA, after 2 ± 1.3 months and 4.6 ± 1.3 months for the ocular coherence tomography, and after 1.3 ± 0.7 months and 4.4 ± 1 months for the IOP. We included 14 patients (20 eyes, 20 implant injections) with cystoid macular edema (78%), vasculitis (7%), choroiditis (7%), and vasculitis associated with choroiditis (7%). Before the injection, mean visual acuity was 0.4 ± 0.5 logMAR (logarithm of the minimum angle of resolution) that improved to 0.3 ± 0.5 logMAR (P = 0.0002) after 1.5 ± 0.8 months and to 0.3 ± 0.5 logMAR (P = 0.005) after 4.4 ± 0.9 months. A statistically significant decrease of macular thickness was observed both at 2 ± 1.3 months and at 4.6 ± 1.3 months after IVT-DI. Mean IOP was 16 ± 5 mmHg before injections, 18 ± 6 mmHg (P = 0.13) at 1.3 ± 0.7 months, and 15 ± 4 mmHg (P = 0.65) at 4.4 ± 1 months. By Kaplan-Meier analysis, we found that after 3.3 months, 17% of the eyes still present a BCVA amelioration ≥0.3 logMAR. In our patients with active noninfectious uveitis, injection of a first single dexamethasone implant was found to improve visual acuity and decrease macular thickness without significant increase of IOP, although the effect seems limited in time.

  17. Overnight Dexamethasone Suppression Test in the Diagnosis of Cushing's Disease

    Directory of Open Access Journals (Sweden)

    Fatemeh Esfahanian

    2010-08-01

    Full Text Available Realizing the cause of Cushing's Syndrome (CS is one of the most challenging processes in clinical endocrinology. The long high dose dexamethasone suppression test (standard test is costly and need an extended inpatient stay. In this study we want to show the clinical utility of the overnight 8 mg dexamethasone suppression test (DST for differential diagnosis of CS in a referral center. Retrospectively from 2002-2005 we selected the patients of endocrinology ward in Imam hospital who were admitted with the diagnosis of Cushing syndrome and had 8 mg DST (modified test along with classic DST. In modified test a decrease in an 8 AM serum cortisol level of 50% or more is thought to indicate suppression and we compared the results of modified test with standard test. This test had been done on 42 patients: 10 male (23% and 32 female (76%. The mean age of patients was 31.39 (15-63, 32 with proven pituitary Cushing's disease, 7 with primary adrnal tumors and 3 with ectopic ACTH syndrome. The standard test according to 50% suppression of UFC had 90.62% sensitivity, and according to 90% suppression had 43.75% sensitivity. The sensitivity of this test was 71.85% for serum cortisol suppression. The modified test (8 mg overnight DST had 78% sensitivity. All of these tests had 100% specificity for the diagnosis of Cushing's disease. The positive predictive vale (PPV of all of these tests was 100%. The negative predictive value (NPV of modified test for the diagnosis of Cushing's disease was 58.82%. In standard test the NPV of serum cortisol was 52.6%, UFC 50% had 76.9% NPV and UFC 90% had 35.7% NPV. The results of serum cortisol suppression in modified test is better than standard test. Although 50% suppression of UFC in standard test had greater sensitivity than modified test, collecting of urine is difficult, time consuming and needing hospitalization, so we advice modified test that is much simpler and more convenient instead of standard test in the first

  18. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study.

    Science.gov (United States)

    Invernizzi, Rosangela; Quaglia, Federica; Klersy, Catherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L

    2015-11-01

    Hereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of thalidomide for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia that is refractory to standard therapy. We recruited patients aged 17 years or older with hereditary haemorrhagic telangiectasia who had severe recurrent epistaxis refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave patients thalidomide at a starting dose of 50 mg/day orally. If they had no response, we increased the thalidomide dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After patients had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of thalidomide measured as the percentage of patients who had reductions of at least one grade in the frequency, intensity, or duration of epistaxis. We followed up patients each month to assess epistaxis severity score and transfusion need, and any adverse events were reported. We included all patients who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224. Between Dec 1, 2011, and May 12, 2014, we enrolled 31 patients. Median follow-up was 15·9 months (IQR 10·1-22·3). Three (10%, 95% CI 2-26) patients had a complete response, with bleeding stopped, 28 (90%, 95% CI 74-98) patients had partial responses

  19. Comparison of the effects of intravitreal bevacizumab and dexamethasone in experimental posterior penetrating eye injury

    Directory of Open Access Journals (Sweden)

    Ayse Oner

    2018-04-01

    Full Text Available AIM: To compare the effects of intravitreal anti-vascular endothelial growth factor (VEGF and dexamethasone in an experimental rabbit model of posterior penetrating ocular injury. METHODS: Thirty white New Zealand rabbits were included in the study. A posterior penetrating ocular injury was performed at the superotemporal quadrant. They were randomly divided into three groups. The rabbits in group 1 received intravitreal dexamethasone, in group 2 they received intravitreal bevacizumab and those in group 3 received intravitreal physiological saline solution in both eyes. All eyes were examined ophthalmologically on the 1st, 3rd, 7th, 14th and 28th days following the injury and the clinical findings were scored. On the day 28, the eyes were enucleated, evaluated and scored macroscopically, histopathologically and scanning electron microscopically. RESULTS: The median clinical score on the 14th and 28th days and the median macroscopic score of the dexamethasone group was significantly better than that of control (P=0.004, 0.018. Dexamethasone group was also better than that of bevacizumab group but the differences did not reach statistical significance. Retinal detachment rate was 8.3%, 16.6% and 12.5% in the dexamethasone group, bevacizumab group and control group, respectively (P=0.476. More extensive fibrocelluler proliferations were observed in controls compared with dexamethasone and bevacizumab groups. But these differences did not reach the statistical significance (P=0.538. In scanning electron microscopy all groups showed fibreous stalk and dense collagen fibrils in vitreous. CONCLUSION: This study shows that intravitreal injection of both dexamethasone and bevacizumab may reduce the intraocular fibrous proliferation after an experimental posterior penetrating ocular injury in rabbits.

  20. Dexamethasone as adjuvant therapy in the treatment of invasive meningococcal diseases.

    Science.gov (United States)

    Tolaj, Ilir; Dreshaj, Shemsedin; Qehaja, Emine; Tolaj, Jasmina; Doda-Ejupi, Teuta; Mehmeti, Murat

    2010-01-01

    With this study we want to evaluate the role of dexamethasone adjuvant treatment in different clinical forms of invasive meningococcal diseases. WORK METHODS: This was a randomized, open label trial that was conducted in 147 individuals with meningococcal sepsis. All of the cases have been divided in two groups: (1) Cases with meningococcal disease and CNS infection, and (2) Cases with meningococcal disease and no affection of the CNS. Cases from both groups were treated with dexamethasone, 0.15 mg/kg, every 6 h, for 4 (four) days, as adjuvant therapy. Cases which were not treated with dexamethasone were used as control group. From overall number of cases, in 130 of them, the meningococcal disease was accompanied with meningitis; in other 17 cases only signs of sepsis were present. In both clinical forms, the dexamethasone was used in 92 cases. The higher mortality rate is registered among the cases without meningitis, 17.65%, compared with 6.92% which is registered among cases with meningitis. The overall mortality rate among all cases was 8.2%. The significant difference was recorded only on CSF sugar level between two groups (treated or not with dexamethasone) on the day 1-4 of the hospitalization. Our epidemiological data are in correlation with data from other epidemiological studies. Most of the cases 69.4%, were more than 12 hours sick at home before the hospitalization, 7.5 % of cases were hospitalized within 12 hours from the onset of the diseases, while 23.1% of cases data are missing. This is in correlation with similar data from other studies. Dexamethasone has a limited effect on outcome of the invasive meningococcal disease. Dexamethasone had some effect only during the days of administration in cases with clinical form of sepsis with meningitis, by normalizing the values of CSF sugar earlier.

  1. Adverse effects of parenteral dexamethasone in the treatment of pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Mohammad Jamal Uddin

    2016-08-01

    Full Text Available Background: Pemphigus vulgaris is associated with high morbidity as well as significant mortality rate. Today the risk of death in pemphigus from the side effect of oral prednisolone is greater than risk of death from the disease itself. Objec­tive: To observe the adverse effects of parenteral dexamethasone compared with oral prednisolone in the treatment of pemphigus vulgaris. Methods: An interventional study was carried out in the department of Dermatology and Venereol­ogy, Bangabandu Sheikh Mujib Medical University, Dhaka, Bangladesh. Total number of patients was thirty and among them fifteen patients were treated with parenteral dexamethasone (Group-A and other fifteen were treated with oral prednisolone (Group-B. Results: The study showed statistically significant differences of skin lesion as well as mucosal lesion of pemphigus after 6 weeks of therapy between of two groups (P<0.05. The most common adverse effects were increased body weight(40%, increased appetite(40%, and puffy face(40% in dexamethasone group. In prednisolone group, these side effects were 60% of the subjects. Other side effects in dexamethasone group were hyperglycemia (33.33%, hypertension (26.66%, and sleep disturbance (13.33%. In prednisolone group, other side effects were hyperglycemia(33.33%, hypertension(40%, gastritis (33.33%, nausea, vomiting (13.33% in each , reactivation of tuberculosis, herpes zoster infection, sleep disturbance, and mood change were 6.66% in each group. Conclusion: In the light of the findings of the study, we conclude that each of the treatment of dexamethasone group and prednisolone group is individually effective and safe in the treatment of pemphigus vulgaris but adverse effects are less in parenteral dexamethasone group than oral prednisolone group. So parenteral dexamethasone can be used as an alternative drug in the treatment of pemphigus vulgaris.

  2. Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

    Science.gov (United States)

    Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

    2016-02-01

    Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

  3. Experimental study on effect of dexamethasone to the in-stent restenosis after vascular intervention

    International Nuclear Information System (INIS)

    Wang Jianbo; Yang Jianyong; Chen Wei; Zhuang Wenquan; Li Jiaping; Zhang Longjuan

    2007-01-01

    Objective: To evaluate the effect of dexamethasone to the cultured rat thoracic aortic smooth muscle cells (SMC) in vitro, and explore the role on it's prevention and cure for the in-stent restenosis after vascular intervention. Methods: The rat thoracic aortic SMC were harvested and cultured for six to ten passages. The cultured SMC were synchronized and then restimutated to enter the cell cycle, and treated with incremental concentrations of dexamethasone or without dexamethasone as control. The proliferative assay was performed with MTT method in the different time points after treatment. RT-PCR was performed to assay the level of proliferating cell nuclear antigen (PCNA) mRNA. Results: 1. Dexamethasone progressively inhibited rat aortic SMC proliferation in a concentration-dependent fashion. The A value was statistically significant for different concentrations (F=36.02, P -6 and 10 -5 mol/L (P=0.065) or between 10 -11 mol/L and control group (P 0.567). 2. RT-PCR suggested dexamethasone significantly decreased rat aortic SMC PCNA mRNA transcription in a concentration-dependent fashion. Statistical analysis indicated F=15.407 and P -9 or 10 -11 mol/L groups by post hoc analysis. Conclusions: Dexamethasone inhibits rat aortic SMC proliferation in a concentration- dependent fashion. The data suggest that effective action concentration is 10 -7 mol/L with persistent time up to 96 hours or more. Dexamethasone may play the inhibit role to SMC at lower concentration with prolonging action time. (authors)

  4. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma

    DEFF Research Database (Denmark)

    San-Miguel, Jesús F; Hungria, Vânia T M; Yoon, Sung-Soo

    2014-01-01

    with bortezomib (1·3 mg/m(2) on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression...

  5. Dexamethasone Suppresses Oxysterol-Induced Differentiation of Monocytic Cells

    Directory of Open Access Journals (Sweden)

    Yonghae Son

    2016-01-01

    Full Text Available Oxysterol like 27-hydroxycholesterol (27OHChol has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined whether dexamethasone (Dx affects 27OHChol-induced differentiation using THP-1 cells. Treatment of monocytic cells with Dx resulted in almost complete inhibition of transcription and surface expression of CD80, CD83, and CD88 induced by 27OHChol. Elevated surface levels of MHC class I and II molecules induced by 27OHChol were reduced to basal levels by treatment with Dx. A decreased endocytosis ability caused by 27OHChol was recovered by Dx. We also examined effects of Dx on expression of CD molecules involved in atherosclerosis. Increased levels of surface protein and transcription of CD105, CD137, and CD166 by treatment with 27OHChol were significantly inhibited by cotreatment with Dx. These results indicate that Dx inhibits 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules whose levels are associated with atherosclerosis. In addition, we examined phosphorylation of AKT induced by 27OHChol and effect of Dx, where cotreatment with Dx inhibited the phosphorylation of AKT. The current study reports that Dx regulates oxysterol-mediated dendritic cell differentiation of monocytic cells.

  6. Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.

    Directory of Open Access Journals (Sweden)

    M Carme Coll Ferrer

    Full Text Available Lysozyme dextran nanogels (NG have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with "stealth" properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab directed to Intercellular Adhesion Molecule-1(ICAM-NG, whereas IgG conjugated NG (IgG-NG are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG; and, ii DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation.

  7. Self-assembled rosette nanotubes encapsulate and slowly release dexamethasone

    Directory of Open Access Journals (Sweden)

    Chen Y

    2011-05-01

    Full Text Available Yupeng Chen1,2, Shang Song2, Zhimin Yan3, Hicham Fenniri3, Thomas J Webster2,41Department of Chemistry, Brown University, Providence, RI, USA; 2School of Engineering, Brown University, Providence, RI, USA; 3National Institute for Nanotechnology and Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada; 4Department of Orthopedics, Brown University, Providence, RI, USAAbstract: Rosette nanotubes (RNTs are novel, self-assembled, biomimetic, synthetic drug delivery materials suitable for numerous medical applications. Because of their amphiphilic character and hollow architecture, RNTs can be used to encapsulate and deliver hydrophobic drugs otherwise difficult to deliver in biological systems. Another advantage of using RNTs for drug delivery is their biocompatibility, low cytotoxicity, and their ability to engender a favorable, biologically-inspired environment for cell adhesion and growth. In this study, a method to incorporate dexamethasone (DEX, an inflammatory and a bone growth promoting steroid into RNTs was developed. The drug-loaded RNTs were characterized using diffusion ordered nuclear magnetic resonance spectroscopy (DOSY NMR and UV-Vis spectroscopy. Results showed for the first time that DEX can be easily and quickly encapsulated into RNTs and released to promote osteoblast (bone-forming cell functions over long periods of time. As a result, RNTs are presented as a novel material for the targeted delivery of hydrophobic drugs otherwise difficult to deliver.Keywords: nanotubes, drug delivery, self-assembly, physiological conditions

  8. Dexamethasone impairs hypoxia-inducible factor-1 function

    International Nuclear Information System (INIS)

    Wagner, A.E.; Huck, G.; Stiehl, D.P.; Jelkmann, W.; Hellwig-Buergel, T.

    2008-01-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of α- and β-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1α levels in the cytosol of HepG2 cells, while nuclear HIF-1α levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in a reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients

  9. Dexamethasone-suppression adrenal scintigraphy in hyperandrogenism: concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Gross, M.D.; Freitas, J.E.; Swanson, D.P.; Woodbury, M.C.; Schteingart, D.E.; Beierwaltes, W.H.

    1981-01-01

    To assess the contribution of adrenal-derived androgens in women with hirsutism, adrenal scintigrams under dexamethasone suppression (DS) were performed on 35 women with increasing facial or body hair and irregular or absent menses. Based upon the DS regimen chosen (8 mg/d for 2 days or 4 md/d for 7 days before the injection of 6..beta..-(/sup 131/I)iodomethylnorcholesterol), three imaging patterns were identified. The first was the absence of uptake before 3 days (8-mg DS) or before 5 days (4-mg DS) after injection. This imaging pattern was seen in 17 of the 35 patients studied and was considered normal. The second pattern was bilateral uptake earlier than 3 days (8-mg DS regimen) or 5 days (4-mg DS) after injection. This was seen in 13 of the 35 patients and was interpreted as bilateral early visualization. Adrenal-vein catheterization performed on six patients with this pattern showed increased adrenal-vein testosterone. The third pattern, observed in five patients, was unilateral early visualization, which in four cases investigated to date was the result of an adrenocortical adenoma. This study confirms the adrenal cortex as a source of androgens in women with hirsutism and hyperandrogenism and demonstrates that DS adrenal scintigraphy can be utilized to identify those women in whom adrenal-derived androgens contribute to their hyperandrogenism.

  10. Up-regulation of the alligator CYP3A77 gene by toxaphene and dexamethasone and its short term effect on plasma testosterone concentrations

    International Nuclear Information System (INIS)

    Gunderson, M.P.; Kohno, S.; Blumberg, B.; Iguchi, T.; Guillette, L.J.

    2006-01-01

    In this study we describe an alligator hepatic CYP3A gene, CYP3A77, which is inducible by dexamethasone and toxaphene. CYP3A plays a broad role in biotransforming both exogenous compounds and endogenous hormones such as testosterone and estradiol. Alligators collected from sites in Florida that are contaminated with organochlorine compounds exhibit differences in sex steroid concentrations. Many organochlorine compounds induce CYP3A expression in other vertebrates; hence, CYP3A induction by organochlorine contaminants could increase biotransformation and clearance of sex steroids by CYP3A and provide a plausible mechanism for the lowering of endogenous sex steroid concentrations in alligator plasma. We used real time PCR to examine whether known and suspected CYP3A inducers (dexamethasone, metyrapone, rifampicin, and toxaphene) up-regulate steady state levels of hepatic CYP3A77 transcript to determine if induction patterns in female juvenile alligators are similar to those reported in other vertebrates and whether toxaphene, an organochlorine compound found in high concentrations in Lake Apopka alligators, induces this gene. Estrogen receptor α (ERα), estrogen receptor β (ERβ), androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), and steroid-xenobiotic receptor (SXR) transcripts were also measured to determine whether any of these nuclear receptors are also regulated by these compounds in alligators. Dexamethasone (4.2-fold) and toxaphene (3.5-fold) significantly induced CYP3A77 gene transcript, whereas rifampicin (2.8-fold) and metyrapone (2.1-fold) up-regulated ERβ after 24 h. None of the compounds significantly up-regulated AR, ERα, GR, PR, or SXR over this time period. Plasma testosterone (T) did not change significantly after 24 h in alligators from any of the treatment groups. Dexamethasone treated animals exhibited a strong relationship between the 24 h plasma T concentrations and CYP3A77 (R 2 = 0.9, positive) and SXR (R 2

  11. Effects of dexamethasone coadministered with oseltamivir on the pharmacokinetics of oseltamivir in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Jang K

    2017-03-01

    Full Text Available Kyungho Jang,1,2,* Min-Kyoung Kim,3,4,* Jaeseong Oh,1 SeungHwan Lee,1 Joo-Youn Cho,1 Kyung-Sang Yu,1 Tai Kiu Choi,3 Sang-Hyuk Lee,3,4 Kyoung Soo Lim4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, 3Department of Psychiatry, 4Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea *These authors contributed equally to this work Purpose: Oseltamivir is widely used in the treatment and prophylaxis of influenza A and B viral infections. It is ingested as an oral prodrug that is rapidly metabolized by carboxylesterase 1 (CES1 to its active form, oseltamivir carboxylate. Dexamethasone is also used in the treatment of acute respiratory distress syndrome, a severe complication of influenza; however, its influence on the pharmacokinetics (PK of oseltamivir is controversial. The aim of this study was to investigate the effects of coadministering oseltamivir and dexamethasone on the PK of oseltamivir in healthy volunteers. Methods: An open-label, two-period, one-sequence, multiple-dose study was conducted in 19 healthy male volunteers. Oseltamivir (75 mg was orally administered on Day 1 and Day 8, and dexamethasone (1.5 mg was administered once daily from Day 3 to Day 8. Serial blood and urine samples were collected for PK analysis of oseltamivir and oseltamivir carboxylate on Day 1 and Day 8. Oseltamivir and oseltamivir carboxylate concentrations in plasma and urine were determined using liquid chromatography–tandem mass spectrometry. Results: Area under the plasma concentration–time curve (AUC of oseltamivir and oseltamivir carboxylate decreased after dexamethasone treatment for 6 days. The geometric mean ratio (90% confidence interval of the metabolic ratio

  12. Inductive Monitoring System (IMS)

    Data.gov (United States)

    National Aeronautics and Space Administration — IMS: Inductive Monitoring System The Inductive Monitoring System (IMS) is a tool that uses a data mining technique called clustering to extract models of normal...

  13. Dexamethasone PONV prophylaxis alters the hypothalamic-pituitary-adrenal axis after transsphenoidal pituitary surgery.

    Science.gov (United States)

    Burkhardt, Till; Rotermund, Roman; Schmidt, Nils-Ole; Kiefmann, Rainer; Flitsch, Jörg

    2014-07-01

    Postoperative nausea and vomiting (PONV) is common after general anesthesia and are reported by approximately 20% to 25% of all patients and up to 39% of patients undergoing neurosurgical procedures. The most common standard prophylaxis is a single application of 4 mg of dexamethasone before initiating anesthesia. Dexamethasone is known to suppress adreno-corticotroph hormone and cortisol levels. The objective was to find out whether this prophylaxis has an effect on the postoperative levels of cortisol in patients undergoing transsphenoidal pituitary surgery, and therefore simulates pituitary deficiency. A retrospective analysis of the files of 136 consecutive patients who were operated during a course of 6 months were included. Nineteen patients with a known history of PONV received a standard dose of 4 mg of dexamethasone perioperatively. Blood tests were drawn at the first postoperative day and were compared with blood tests of patients who had no history of PONV and therefore received no prophylaxis. Patients who were treated with a dexamethasone PONV prophylaxis showed no significant changes in cortisol levels; preoperative median of 93 μg/L (range, 39 to 427) and a postoperative median of 87 μg/L (range, 10 to 733; P=0.798) opposed to patients who did not receive such treatment; preoperative cortisol 114 μg/L (range, 10 to 387) and postoperative levels of 273 μg/L (range, 10 to 1352; Ptranssphenoidal surgery, the probability that dexamethasone PONV prophylaxis suppresses postoperative cortisol levels should be considered.

  14. Long-term Effects of Dexamethasone on Reproductive Parameters in Male Mice

    Directory of Open Access Journals (Sweden)

    jalogoden Gouyandeh

    2015-02-01

    Full Text Available Background & aim: The adverse effect of chemical drugs such as dexamethasone as anti-inflammatory -steroidal drugs on different body systems and infertility and reproductive efficiency is of concern. The purpose of this study was to evaluate the long-term effects of dexamethasone on the reproductive system in male rats. Methods: In the present experimental study, fifty matured male mice were divided into five groups including control, placebo and three treatment groups. Control group had no injections, placebo group only received normal saline and treatments groups received dexamethasone (0.1, 0.5 and 1 mg/kg which was injected in peritoneum every other day for a period of twenty days. Their Testosterone was measured by ELISA and testes were dissected for histological examination. The data were analyzed using SPSS 11.5 software. Results: Significant increases were shown in FSH level in all three groups treated with dexamethasone. LH in treatment group of 0.1 mg/kg decreased, but at dose of 1 mg/kg increased significantly.Testosterone levels in a dose of 1 mg/kg significantly increased compared with the control group (p<0.05. However, testis weight, the rate of testicular germ cells, primary spermatocytes, epididymal sperm and fertility significantly increased in all three groups (p<0.05. Conclusion: Dexamethasone had a negative effect on reproduction therefore, the use of this medication at different doses and time periods considers the possible complications beforehand. Keywords: .

  15. Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Monica Argenziano

    2017-06-01

    Full Text Available Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic lupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented adverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the sustained delivery of dexamethasone were designed to increase both bioavailability and duration of the administered drug and reducing the therapeutic dose. Hydrogels are soft materials consisting of water-swollen cross-linked polymers to which the insertion of cyclodextrin (CD moieties adds hydrophobic drug-complexing sites. Polyamidoamines (PAAs are biocompatible and biodegradable polymers apt to create CD moieties in hydrogels. In this work, β or γ-CD/PAA nanogels have been developed. In vitro studies showed that a pretreatment for 24–48 h with dexamethasone-loaded, β-CD/PAA nanogel (nanodexa inhibits adhesion of Jurkat cells to human umbilical vein endothelial cells (HUVEC in conditions mimicking inflammation. This inhibitory effect was faster and higher than that displayed by free dexamethasone. Moreover, nanodexa inhibited COX-2 expression induced by PMA+A23187 in Jurkat cells after 24–48 h incubation in the 10−8–10−5 M concentration range, while dexamethasone was effective only at 10−5 M after 48 h treatment. Hence, the novel nanogel-dexamethasone formulation combines faster action with lower doses, suggesting the potential for being more manageable than the free drug, reducing its adverse side effects.

  16. Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived from the PK-Eye.

    Science.gov (United States)

    Awwad, Sahar; Day, Richard M; Khaw, Peng T; Brocchini, Steve; Fadda, Hala M

    2017-04-30

    Corticosteroids have long been used to treat intraocular inflammation by intravitreal injection. We describe dexamethasone loaded poly-DL-lactide-co-glycolide (PLGA) microparticles that were fabricated by thermally induced phase separation (TIPS). The dexamethasone loaded microparticles were evaluated using a two-compartment, in vitro aqueous outflow model of the eye (PK-Eye) that estimates drug clearance time from the back of the eye via aqueous outflow by the anterior route. A dexamethasone dose of 0.20±0.02mg in a 50μL volume of TIPS microparticles resulted in a clearance t 1/2 of 9.6±0.3days using simulated vitreous in the PK-Eye. Since corticosteroids can also clear through the retina, it is necessary to account for clearance through the back of the eye. Retinal permeability data, published human ocular pharmacokinetics (PK) and the PK-Eye clearance times were then used to establish in vitro in vivo correlations (IVIVCs) for intraocular clearance times of corticosteroid formulations. A t 1/2 of 48h was estimated for the dexamethasone-TIPS microparticles, which is almost 9 times longer than that reported for dexamethasone suspension in humans. The prediction of human clearance times of permeable molecules from the vitreous compartment can be determined by accounting for drug retinal permeation and determining the experimental clearance via the anterior aqueous outflow pathway using the PK-Eye. Copyright © 2017. Published by Elsevier B.V.

  17. Inductive Reasoning and Writing

    Science.gov (United States)

    Rooks, Clay; Boyd, Robert

    2003-01-01

    Induction, properly understood, is not merely a game, nor is it a gimmick, nor is it an artificial way of explaining an element of reasoning. Proper understanding of inductive reasoning--and the various types of reasoning that the authors term inductive--enables the student to evaluate critically other people's writing and enhances the composition…

  18. Mechanisms of interleukin-2-induced hydrothoraxy in mice: protective effect of endotoxin tolerance and dexamethasone and possible role of reactive oxygen intermediates.

    Science.gov (United States)

    Faggioni, R; Allavena, P; Cantoni, L; Carelli, M; Demitri, M T; Delgado, R; Gatti, S; Gnocchi, P; Isetta, A M; Paganin, C

    1994-04-01

    Interleukin (IL)-2 is known to induce vascular leak syndrome (VLS), which was suggested to be mediated by immune system-derived cytokines, including tumor necrosis factor (TNF). To characterize the role of TNF in IL-2 toxicity in C3H/HeN mice, we used two approaches to downregulate TNF production in vivo: treatment with dexamethasone (DEX) and induction of endotoxin (lipopolysaccharide) (LPS) tolerance by a 4-day pretreatment with LPS (35 micrograms/mouse/day). Mice were then treated with IL-2 for 5 days (1.8 x 10(5) IU/mouse, twice daily). Both DEX and LPS tolerance blocked development of hydrothorax in IL-2-treated mice and inhibited TNF induction. DEX and LPS tolerance also ameliorated IL-2 toxicity in terms of decrease in food intake and inhibited the increase of the acute-phase protein, serum amyloid A (SAA). The IL-2 activation of splenic natural killer (NK) cell activity was also diminished by DEX and, to a lesser extent, by LPS-tolerance. Treatment with IL-2 also caused induction of the superoxide-generating enzyme xanthine oxidase (XO) in tissues and serum and induced bacterial translocation in the mesenteric lymph nodes (MLN). These data suggest that multiple mechanisms, including NK cell activity, cytokines, and reactive oxygen intermediates, might be important in the vascular toxicity of IL-2.

  19. Rats Born to Mothers Treated with Dexamethasone 15 cH Present Changes in Modulation of Inflammatory Process

    Directory of Open Access Journals (Sweden)

    Leoni V. Bonamin

    2012-01-01

    Full Text Available As little information about the effect of ultra high dilutions of glucocorticoid in reproduction is available in the literature, pregnant female Wistar rats (N=12 were blindly subcutaneously treated during all gestational and lactation period with: dexamethasone 4 mg/kg diluted into dexamethasone 15 cH (mixed; or dexamethasone 4 mg/kg diluted in water; or dexamethasone 15 cH, or vehicle. Parental generation had body weight, food and water consumption monitored. The F1 generation was monitored regarding to newborn development. No birth occurred in both groups treated with dexamethasone 4 mg/kg. After 60 days from birth, 12 male F1 rats were randomly selected from each remaining group and inoculated subcutaneously with 1% carrageenan into the footpad, for evaluation of inflammatory performance. Edema and histopathology of the footpad were evaluated, using specific staining methods, immunohistochemistry and digital histomorphometry. Mothers treated with mixed dexamethasone presented reduced water consumption. F1 rats born to dexamethasone 15 cH treated females presented significant increase in mast cell degranulation, decrease in monocyte percentage, increase in CD18+ PMN cells, and early expression of ED2 protein, in relation to control. The results show that the exposure of parental generation to highly diluted dexamethasone interferes in inflammation modulation in the F1 generation.

  20. Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery : A randomised trial

    NARCIS (Netherlands)

    Dieleman, J. M.; de Wit, G. A.; Nierich, A. P.; Rosseel, P. M.; van der Maaten, J. M.; Hofland, J.; Diephuis, J. C.; de Lange, F.; Boer, C.; Neslo, R. E.; Moons, K. G.; van Herwerden, L. A.; Tijssen, J. G.; Kalkman, C. J.; van Dijk, D.

    Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre,

  1. Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery: a randomised trial

    NARCIS (Netherlands)

    Dieleman, J. M.; de Wit, G. A.; Nierich, A. P.; Rosseel, P. M.; van der Maaten, J. M.; Hofland, J.; Diephuis, J. C.; de Lange, F.; Boer, C.; Neslo, R. E.; Moons, K. G.; van Herwerden, L. A.; Tijssen, J. G.; Kalkman, C. J.; van Dijk, D.

    2017-01-01

    Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre,

  2. Evaluation of the release behavior of the dexamethasone embedded in polycarbonate polyurethane membranes: an in vitro study

    International Nuclear Information System (INIS)

    Kim, Dong Hyun; Kang, Sung Gwon; Lee, Chul Gab; Park, Sang Soo; Lee, Don Haeng; Lee, Gyu Baek; Song, Ho Young

    2003-01-01

    To evaluate the release behavior of dexamethasone embedded in a polycarbonate polyurethane membrane. Both water-soluble and water-insoluble dexamethasone were tested, and the release behavior of five water-insoluble dexamethasone films of different thickness (78 to 211 μm) was also evaluated. The amount of dexamethasone used was 10% of the total weight of the polyurethan film mass. Each film was placed in a centrifuge tube containing 25 ml of 0.1-M neutral phosphate buffer, and the tubes were placed in a shaking incubator to quantify the amount of drug released into the buffer, absorption spectroscopy (λ max=242 nm) was employed. In the test involving water-soluble dexamethasone, 60%, of the drug was released during the first two hours of the study. Films containing water-insoluble dexamethasone, on the other hand, released 40%, 60% and 75% of the dexamethasone in one, three and seven days, respectively. Both types of film maintained low-dose drug release for 28 days. When release behavior was compared between water-insoluble films of different thickness, thicker film showed less initial burst and more sustained release. Dexamethasone release behavior varies according to drug solubility and membrane thickness, and may thus be conrolled

  3. Dexamethasone intravitreal implant (Ozurdex) for the treatment of pediatric uveitis.

    Science.gov (United States)

    Bratton, Monica L; He, Yu-Guang; Weakley, David R

    2014-04-01

    To report our experience using Ozurdex (Allergan, Irvine, CA), a biodegradable intravitreal implant containing of 0.7 mg of dexamethasone approved for use in adults with noninfectious uveitis in adults, in the treatment of pediatric uveitis. The medical records of consecutive patients with noninfectious posterior uveitis who were unresponsive to standard treatment and subsequently received the Ozurdex implant from March 2011 to March 2013 were retrospectively reviewed. A total of 14 eyes of 11 patients (mean age, 10.1 years; range 4-12) received 22 Ozurdex implants during the study period. Of the 11 patients, 7 had idiopathic intermediate or posterior uveitis, 1 had sympathetic ophthalmia, 2 had juvenile idiopathic arthritis, and 1 had sarcoidosis. All patients were uncontrolled with standard treatment, including topical or sub-Tenon's or systemic corticosteriods and/or immune-modulation. Visual acuity improved after Ozurdex implant in 5 of 8 patients (63%). Intraocular inflammation was controlled or improved after 17 of 22 of implants (12 eyes [77%]). The frequency of topical corticosteroids was decreased and/or discontinued after 18 of 22 implants (12 eyes [82%]). Complications included implant migration into the anterior chamber (4 aphakic eyes), increased intraocular pressure (5 eyes), and progression of a preexisting cataract (1 eye). The uveitis reoccurred in 57% of eyes at 4.3 months (2-7 months) after injection. The Ozurdex implant in combination with systemic immunomodulatory therapy resulted in improved visual acuity, control of intraocular inflammation, and a decrease in corticosteroid use. In the majority of eyes the uveitis reoccurred around 4 months after injection. The adverse events in our study are similar to those identified in adult studies. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  4. Variable effects of dexamethasone on protein synthesis in clonal rat osteosarcoma cells

    International Nuclear Information System (INIS)

    Hodge, B.O.; Kream, B.E.

    1988-01-01

    We examined the effects of dexamethasone on protein synthesis in clonal rat osteoblastic osteosarcoma (ROS) cell lines by measuring the incorporation of [ 3 H]proline into collagenase-digestible and noncollagen protein in the cell layer and medium of the cultures. In ROS 17/2 and subclone C12 of ROS 17/2.8, dexamethasone decreased collagen synthesis with no change in DNA content of the cultures. In ROS 17/2.8 and its subclone G2, dexamethasone stimulated collagen and noncollagen protein synthesis, with a concomitant decrease in the DNA content of the cells. These data indicate that ROS cell lines are phenotypically heterogeneous and suggest that in normal bone there may be distinct subpopulations of osteoblasts with varying phenotypic traits with respect to the regulation of protein synthesis

  5. Competitive inhibition of [3H]dexamethasone binding to mammary glucocorticoid receptor by leupeptin

    International Nuclear Information System (INIS)

    Hsieh, L.C.C.; Su, C.; Markland, F.S. Jr.

    1987-01-01

    The inhibitory effect of leupeptin on [ 3 H]dexamethasone binding to the glucocorticoid receptor from lactating goat mammary cytosol has been studied. Leupeptin (10 mM) caused a significant (about 35%) inhibition of [ 3 H]dexamethasone binding to glucocorticoid receptor. Binding inhibition is further increased following filtration of unlabeled cytosolic receptor through a Bio-Gel A 0.5-m column. Binding inhibition was partially reversed by monothioglycerol at 10 mM concentration. A double reciprocal plot revealed that leupeptin appears to be a competitive inhibitor of [ 3 H]dexamethasone binding to the glucocorticoid receptor. Low salt sucrose density gradient centrifugation revealed that the leupeptin-treated sample formed a slightly larger (approximately 9 S) receptor complex (leupeptin-free complex sediments at 8 S)

  6. Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty

    DEFF Research Database (Denmark)

    Mathiesen, O.; Jacobsen, L.S.; Holm, H.E.

    2008-01-01

    Background. Optimal pain treatment with minimal side-effects is essential for early mobility and recovery in patients undergoing total hip arthroplasty. We investigated the analgesic effect of pregabalin and dexamethasone in this surgical procedure. Methods. One hundred and twenty patients were...... randomly allocated to either Group A (placebo), Group B (pregabalin 300 mg), or Group C (pregabalin 300 mg+dexamethasone 8 mg). The medication and acetaminophen 1 g were given before operation. Spinal anaesthesia was performed. Postoperative pain treatment was with acetaminophen 1 g three times daily...... with the other groups. Conclusions. Pregabalin resulted in a 50% reduction in 24 h postoperative morphine requirements. This was not associated with a reduced incidence of nausea or vomiting. Pregabalin resulted in increased levels of sedation. Combining pregabalin and dexamethasone provided no additional...

  7. Induction machine handbook

    CERN Document Server

    Boldea, Ion

    2002-01-01

    Often called the workhorse of industry, the advent of power electronics and advances in digital control are transforming the induction motor into the racehorse of industrial motion control. Now, the classic texts on induction machines are nearly three decades old, while more recent books on electric motors lack the necessary depth and detail on induction machines.The Induction Machine Handbook fills industry's long-standing need for a comprehensive treatise embracing the many intricate facets of induction machine analysis and design. Moving gradually from simple to complex and from standard to

  8. Rapamycin sensitizes T-ALL cells to dexamethasone-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Mu Dezhi

    2010-11-01

    Full Text Available Abstract Background Glucocorticoid (GC resistance is frequently seen in acute lymphoblastic leukemia of T-cell lineage (T-ALL. In this study we investigate the potential and mechanism of using rapamycin to restore the sensitivity of GC-resistant T-ALL cells to dexamethasone (Dex treatment. Methods Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl- 2,5-diphenyltetrazolium bromide (MTT assay. Fluorescence-activated cell sorting (FACS analysis was used to analyze apoptosis and cell cycles. Western blot analysis was performed to test the expression of the downstream effector proteins of mammalian target of rapamycin (mTOR, the cell cycle regulatory proteins, and apoptosis associated proteins. Results 10 nM rapamycin markedly increased GC sensitivity in GC-resistant T-ALL cells and this effect was mediated, at least in part, by inhibition of mTOR signaling pathway. Cell cycle arrest was associated with modulation of G1-S phase regulators. Both rapamycin and Dex can induce up-regulation of cyclin-dependent kinase (CDK inhibitors of p21 and p27 and co-treatment of rapamycin with Dex resulted in a synergistic induction of their expressions. Rapamycin did not obviously affect the expression of cyclin A, whereas Dex induced cyclin A expression. Rapamycin prevented Dex-induced expression of cyclin A. Rapamycin had a stronger inhibition of cyclin D1 expression than Dex. Rapamycin enhanced GC-induced apoptosis and this was not achieved by modulation of glucocorticoid receptor (GR expression, but synergistically up-regulation of pro-apoptotic proteins like caspase-3, Bax, and Bim, and down-regulation of anti-apoptotic protein of Mcl-1. Conclusion Our data suggests that rapamycin can effectively reverse GC resistance in T-ALL and this effect is achieved by inducing cell cycles arrested at G0/G1 phase and activating the intrinsic apoptotic program. Therefore, combination of mTOR inhibitor rapamycin with GC containing protocol might be an attracting

  9. Granisetron plus dexamethasone for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: A meta-analysis.

    Science.gov (United States)

    Zhu, Min; Zhou, Chengmao; Huang, Bing; Ruan, Lin; Liang, Rui

    2017-06-01

    Objective This study was designed to compare the effectiveness of granisetron plus dexamethasone for preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic surgery. Methods We searched the literature in the Cochrane Library, PubMed, EMBASE, and CNKI. Results In total, 11 randomized controlled trials were enrolled in this analysis. The meta-analysis showed that granisetron in combination with dexamethasone was significantly more effective than granisetron alone in preventing PONV in patients undergoing laparoscopy surgery. No significant differences in adverse reactions (dizziness and headache) were found in association with dexamethasone. Conclusion Granisetron in combination with dexamethasone was significantly more effective than granisetron alone in preventing PONV in patients undergoing laparoscopic surgery, with no difference in adverse reactions between the two groups. Granisetron alone or granisetron plus dexamethasone can be used to prevent PONV in patients undergoing laparoscopic surgery.

  10. Cortisol secretion after adrenocorticotrophin (ACTH and Dexamethasone tests in healthy female and male dogs

    Directory of Open Access Journals (Sweden)

    Castillo Victor

    2009-08-01

    Full Text Available Abstract Background For the conclusive diagnosis of Cushing's Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs. Methods Seven healthy adult Cocker Spaniels (4 females and 3 males were assigned to a two by two factorial design: 4 dogs (2 females and 2 males received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group. Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal to 4 dogs (2 female and 2 males while the rest was treated with saline solution (control group. Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits. Results and Discussion No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection. Conclusion We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.

  11. Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model.

    Science.gov (United States)

    Tain, You-Lin; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Kuo, Ho-Chang; Huang, Li-Tung

    2014-04-01

    Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  12. Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-α and dexamethasone

    Directory of Open Access Journals (Sweden)

    Walseth Timothy F

    2008-03-01

    Full Text Available Abstract Background CD38 is expressed in human airway smooth muscle (HASM cells, regulates intracellular calcium, and its expression is augmented by tumor necrosis factor alpha (TNF-α. CD38 has a role in airway hyperresponsiveness, a hallmark of asthma, since deficient mice develop attenuated airway hyperresponsiveness compared to wild-type mice following intranasal challenges with cytokines such as IL-13 and TNF-α. Regulation of CD38 expression in HASM cells involves the transcription factor NF-κB, and glucocorticoids inhibit this expression through NF-κB-dependent and -independent mechanisms. In this study, we determined whether the transcriptional regulation of CD38 expression in HASM cells involves response elements within the promoter region of this gene. Methods We cloned a putative 3 kb promoter fragment of the human cd38 gene into pGL3 basic vector in front of a luciferase reporter gene. Sequence analysis of the putative cd38 promoter region revealed one NF-κB and several AP-1 and glucocorticoid response element (GRE motifs. HASM cells were transfected with the 3 kb promoter, a 1.8 kb truncated promoter that lacks the NF-κB and some of the AP-1 sites, or the promoter with mutations of the NF-κB and/or AP-1 sites. Using the electrophoretic mobility shift assays, we determined the binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-κB, AP-1, and GRE sites, and the specificity of this binding was confirmed by gel supershift analysis with appropriate antibodies. Results TNF-α induced a two-fold activation of the 3 kb promoter following its transfection into HASM cells. In cells transfected with the 1.8 kb promoter or promoter constructs lacking NF-κB and/or AP-1 sites or in the presence of dexamethasone, there was no induction in the presence of TNF-α. The binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-κB site and some of the six AP-1 sites was increased by TNF-α, and to

  13. Identification of phototransformation products of thalidomide and mixture toxicity assessment: an experimental and quantitative structural activity relationships (QSAR) approach.

    Science.gov (United States)

    Mahmoud, Waleed M M; Toolaram, Anju P; Menz, Jakob; Leder, Christoph; Schneider, Mandy; Kümmerer, Klaus

    2014-02-01

    The fate of thalidomide (TD) was investigated after irradiation with a medium-pressure Hg-lamp. The primary elimination of TD was monitored and structures of phototransformation products (PTPs) were assessed by LC-UV-FL-MS/MS. Environmentally relevant properties of TD and its PTPs as well as hydrolysis products (HTPs) were predicted using in silico QSAR models. Mutagenicity of TD and its PTPs was investigated in the Ames microplate format (MPF) aqua assay (Xenometrix, AG). Furthermore, a modified luminescent bacteria test (kinetic luminescent bacteria test (kinetic LBT)), using the luminescent bacteria species Vibrio fischeri, was applied for the initial screening of environmental toxicity. Additionally, toxicity of phthalimide, one of the identified PTPs, was investigated separately in the kinetic LBT. The UV irradiation eliminated TD itself without complete mineralization and led to the formation of several PTPs. TD and its PTPs did not exhibit mutagenic response in the Salmonella typhimurium strains TA 98, and TA 100 with and without metabolic activation. In contrast, QSAR analysis of PTPs and HTPs provided evidence for mutagenicity, genotoxicity and carcinogenicity using additional endpoints in silico software. QSAR analysis of different ecotoxicological endpoints, such as acute toxicity towards V. fischeri, provided positive alerts for several identified PTPs and HTPs. This was partially confirmed by the results of the kinetic LBT, in which a steady increase of acute and chronic toxicity during the UV-treatment procedure was observed for the photolytic mixtures at the highest tested concentration. Moreover, the number of PTPs within the reaction mixture that might be responsible for the toxification of TD during UV-treatment was successfully narrowed down by correlating the formation kinetics of PTPs with QSAR predictions and experimental toxicity data. Beyond that, further analysis of the commercially available PTP phthalimide indicated that transformation of

  14. Transcorneal iontophoresis of dendrimers: PAMAM corneal penetration and dexamethasone delivery.

    Science.gov (United States)

    Souza, Joel G; Dias, Karina; Silva, Silas A M; de Rezende, Lucas C D; Rocha, Eduardo M; Emery, Flavio S; Lopez, Renata F V

    2015-02-28

    Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain therapeutic concentrations. Fourth generation polyamidoamine (PAMAM) dendrimers are semi-rigid nanoparticles with surface groups that are easily modified. These dendrimers are known to modulate tight junctions, increase paracellular transport of small molecules and be translocated across epithelial barriers, exhibiting high uptake by different cell lines. The first aim of this study was to investigate the effect of iontophoresis on PAMAM penetration and distribution into the cornea. The second aim was to evaluate, ex vivo and in vivo, the effect of these dendrimers in dexamethasone (Dex) transcorneal iontophoresis. Anionic (PAMAM G3.5) and cationic (PAMAM G4) dendrimers were labeled with fluorescein isothiocyanate (FITC), and their distribution in the cornea was investigated using confocal microscopy after ex vivo anodal and cathodal iontophoresis for various application times. The particle size distribution and zeta potential of the dendrimers in an isosmotic solution were determined using dynamic light scattering and Nanoparticle Tracking Analysis (NTA), where the movement of small particles and the formation of large aggregates, from 5 to 100 nm, could be observed. Transcorneal iontophoresis increased the intensity and depth of PAMAM-FITC fluorescence in the cornea, suggesting improved transport of the dendrimers across the epithelium toward the stroma. PAMAM complexes with Dex were characterized by (13)C-NMR, (1)H-NMR and DOSY. PAMAM G3.5 and PAMAM G4 increased the aqueous solubility of Dex by 10.3 and 3.9-fold, respectively; however, the particle size distribution and zeta potential remained unchanged. PAMAM G3.5 decreased the Dex diffusion coefficient 48-fold compared with PAMAM G4. The ex vivo studies showed that iontophoresis increased the amount of Dex that penetrated into the cornea by 2.9, 5.6 and 3.0-fold for Dex, Dex-PAMAM G4 and Dex-PAMAM G3

  15. Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development

    International Nuclear Information System (INIS)

    Cheng, Xin; Chen, Jian-long; Ma, Zheng-lai; Zhang, Zhao-long; Lv, Shun; Mai, Dong-mei; Liu, Jia-jia; Chuai, Manli; Lee, Kenneth Ka Ho; Wan, Chao; Yang, Xuesong

    2014-01-01

    Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10 −8 –10 −6 μmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly increased

  16. Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Xin; Chen, Jian-long; Ma, Zheng-lai; Zhang, Zhao-long; Lv, Shun; Mai, Dong-mei; Liu, Jia-jia [Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Medicine, Jinan University, Guangzhou 510632 (China); Chuai, Manli [Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH (United Kingdom); Lee, Kenneth Ka Ho; Wan, Chao [Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Yang, Xuesong, E-mail: yang_xuesong@126.com [Department of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Medicine, Jinan University, Guangzhou 510632 (China); Institute of Fetal-Preterm Labor Medicine, Jinan University, Guangzhou 510632 (China)

    2014-11-15

    Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10{sup −8}–10{sup −6} μmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly

  17. Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors in C2C12 myotubes

    NARCIS (Netherlands)

    Maestrone, E; Lagostena, L; Henning, RH; DenHertog, A; Nobile, M

    Three days of treatment with the glucocorticoid dexamethasone (1 nM-mu M) induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine receptor (nAChR) in C2C12 mouse myotubes (EC(50)=10+/-7.3 nM), as assessed by [H-3]alpha-BuTx binding. The maximum increase in binding amounted

  18. Effects of Neonatal Dexamethasone Treatment on the Cardiovascular Stress Response of Children at School Age

    NARCIS (Netherlands)

    Karemaker, Rosa; Karemaker, John M.; Kavelaars, Annemieke; Tersteeg-Kamperman, Marijke; Baerts, Wim; Veen, Sylvia; Samsom, Jannie F.; van Bel, Frank; Heijnen, Cobi J.

    2008-01-01

    OBJECTIVE. The goal was to investigate cardiovascular responses to a psychosocial stressor in school-aged, formerly premature boys and girls who had been treated neonatally with dexamethasone or hydrocortisone because of chronic lung disease. METHODS. We compared corticosteroid-treated, formerly

  19. The influence of betamethasone and dexamethasone on motor development in young rats

    NARCIS (Netherlands)

    Gramsbergen, A; Mulder, EJH

    Synthetic corticosteroids such as dexamethasone and betamethasone are widely used in clinical practice of the perinatal period to enhance lung maturation. However, indications emerged both on the basis of investigations in humans and in experimental animals that such treatment leads to abnormal

  20. Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone : a pilot study

    NARCIS (Netherlands)

    De Keyser, J; Zwanikken, C; Zorgdrager, A; Oenema, D

    The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral

  1. Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis.

    Science.gov (United States)

    Carmichael, J.; Bessell, E. M.; Harris, A. L.; Hutcheon, A. W.; Dawes, P. J.; Daniels, S.; Bessel, E. M.

    1994-01-01

    Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone. PMID:7981069

  2. Low-Dose Dexamethasone Therapy from Infancy of Virilizing Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Stephenson Kerry

    2009-12-01

    Full Text Available Objective. To assess the growth and control of adrenal androgen secretion in children with virilizing congenital adrenal hyperplasia (CAH treated with dexamethasone. Method. We examined doses used, control of adrenal androgen secretion, and growth and skeletal maturation of 8 children with CAH treated with dexamethasone beginning in infancy. Results. 3 boys and 5 girls with classical CAH (17-hydroxyprogesterone at diagnosis >20,000 ng/dL were treated with dexamethasone beginning at diagnosis ( ; all doses were given in the morning using a dosing syringe to administer a 0.1 mg/mL elixir. The children were treated for years over which time the change in bone age to chronological age ratio (BA/CA was . Most recent height Z' scores were , and body mass index (BMI scores were . Late afternoon levels of 17-hydroxyprogesterone, androstenedione, and testosterone were  ng/dL ( nmol/L,  ng/dL ( nmol/L, and  ng/dL; ( nmol/L, respectively. Conclusions. These observations show that low doses of dexamethasone can be used to effectively treat CAH beginning in infancy.

  3. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    International Nuclear Information System (INIS)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O.; Knebel Doeberitz, M. von

    1998-01-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [de

  4. Effect of Submucosal Injection of Dexamethasone on Post-operative Sequelae of Third Molar Surgery

    Directory of Open Access Journals (Sweden)

    S P Deo

    2011-06-01

    Full Text Available Introduction: This study was carried out to evaluate the effects of a single pre-operative sub-mucosal injection of dexamethasone after third molar surgery to see the effects on post-operative discomfort. Methods: This study was a prospective, double-blind, randomized, clinical trial. The subjects were forty patients who underwent surgical removal of the mandibular impacted third molar under local anesthesia and after being randomly assigned to receive either an 8 mg dexamethasone as submucosal injection or a normal saline injection into the lower buccal vestibule adjacent to the third molar. The maximum interincisal distance and facial contours were measured at the baseline and post-surgically on Day 2 and 7. Post-operative pain was evaluated subjectively using a visual analog scale and objectively by counting the number of analgesic tablets used. All subjects were operated upon by the same investigator to minimize the difference from inter-operator variability. Results: There was a signicant difference in the measurements of the degree of swelling and trismus between the two groups on the 2nd post-operative day. In contrast, there was no statistically signicant difference between the groups on the 7th post-operative day. The test group also used fewer analgesics post-operatively. Conclusions: Submucosal injection of dexamethasone after third molar surgery is effective in reducing postoperative swelling and trismus. It also delays the onset of post-operative pain. Keywords: dexamethasone, submucosal injection, third molar, third molar surgery, third molar extraction

  5. Simultaneous Determination of Ciprofloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Eye Drops by HPLC

    Directory of Open Access Journals (Sweden)

    Prakash Katakam

    2012-01-01

    Full Text Available A liquid chromatographic method was developed and validated for the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations. Optimum separation was achieved in less than 5 min using a C18 column (250 mmx4.6 mm i.d, 5μ particle size by isocratic elution. The mobile phase consisting of a mixture of mixed phosphate buffer (pH 4 and acetonitrile (65:35, v/v was used. Column effluents were monitored at 254 nm at a flow rate of 1ml/min. Retention times of ciprofloxacin hydrochloride and dexamethasone sodium phosphate were 2.0 and 3.16 min respectively. The linearity of ciprofloxacin hydrochloride and dexamethasone sodium phosphate was in the range of 3-18 μg/ml and 1-6 μg/ml respectively. Developed method was economical in terms of the time taken and amount of solvent consumed for each analysis. The method was validated and successfully applied to the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations.

  6. Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia.

    Science.gov (United States)

    Lear, Christopher A; Davidson, Joanne O; Mackay, Georgia R; Drury, Paul P; Galinsky, Robert; Quaedackers, Josine S; Gunn, Alistair J; Bennet, Laura

    2018-04-01

    Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.

  7. Comparative Study of Intrathecal Dexamethasone with Epinephrine as Adjuvants to Lidocaine in Cesarean Section

    Directory of Open Access Journals (Sweden)

    Fereshteh Naziri

    2013-09-01

    Full Text Available Background: Different additives have been used with local anesthetics to provide prolonged duration of sensory block in spinal anesthesia. The aim of present study was to evaluate the onset and duration of sensory block of intrathecal dexamethasone and epinephrine as adjuvants to lidocaine in patients who were candidate for cesarean section. Materials and Methods: This double-blind clinical trial research was conducted on 90 pregnant women candidate for cesarean section under spinal anesthesia. Patients were randomly allocated to receive intrathecally either 75 mg hyperbaric lidocaine plus 100 μg epinephrine or 75 mg hyperbaric lidocaine plus 4 mg dexamethasone or 75 mg hyperbaric lidocaine. The onset and duration of sensory block as well as postoperative analgesia were assessed. Results: The time to reach the peak sensory block in lidocaine group was shorter than that of other two groups (p<0.001. Duration of sensory block in the control group, dexamethasone group, and epinephrine group were 64.16±7.99 min, 74.79±12.78 min, and 99.30±10.93 min, respectively (p<0.001. Conclusion: The present research shows that intrathecal dexamethasone and intrathecal epinephrine as adjuvant to lidocaine increases sensory block duration in the women candidate for cesarean section.

  8. Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; Meer, Berend van; Ward-van Oostwaard, Dorien [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); Passier, Robert [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); MIRA, University of Twente (Netherlands); Tertoolen, Leon G.J.; Mummery, Christine L. [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands); Casini, Simona, E-mail: s.casini@amc.uva.nl [Department of Anatomy and Embryology, Leiden University Medical Center, Leiden (Netherlands)

    2015-11-27

    One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation. - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.

  9. The experimental study of the effect of dexamethasone, lidocaine and contrast medium on the activity of collagenase

    International Nuclear Information System (INIS)

    Wu Zhiqun; Liu Weimin; Li Zhonghua; Yang Peng

    2007-01-01

    Objective: To study the effects of hormone, anesthetic and contrast medium on the activities of collagenase lysis. Methods: Nuclear tissues were divided into equal amount for different groups and same units of collagenase were used for the lysis. The only difference in the control group from experimental groups was that there were no dexamethasone, lidocaine or omnipaque but existing in experimental groups. Twenty four hours later, the concentrations of the hydroxyproline were determined in different groups and the data were analyzed by statistical software with computer. Results: 1. The concentrations of hydroxyproline in the dexamethasone group, lidocaine group and omnipaque group were significantly lower than that of control group, especially that of lidocaine group, P value was <0.05 or 0.01. 2. The concentrations of hydroxyproline in the dexamethasone + lidocaine group, dexamethasone + omnipaque group, lidocaine+omnipaque group and dexamethasone + lidocaine + omnipaque group were significantly lower than that of control group; and simultaneously lower in dexamethasone group, lidocaine group, omnipaque group respectively; P value was also <0.05 or 0.01. Conclusion: Dexamethasone, lidocaine and omnipaque can individually inhibit the activity of collagenase at different degrees, so they shouldn't be used together with collagenase in treating the lumber disc herniation. (authors)

  10. Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing (China); Tan, Huaping, E-mail: hptan@njust.edu.cn [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing (China); Hu, Xiaohong [School of Material Engineering, Jinling Institute of Technology, Nanjing (China)

    2015-11-01

    A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels–Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37 °C were studied. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. - Highlights: • A biodegradable hyaluronic acid hydrogel was crosslinked via aqueous Diels–Alder chemistry. • Dexamethasone was covalently immobilized into the hyaluronic acid hydrogel via aqueous Diels–Alder chemistry. • Dexamethasone could be released from the Diels–Alder hyaluronic acid hydrogel in a controlled fashion.

  11. Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering

    International Nuclear Information System (INIS)

    Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

    2015-01-01

    A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels–Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37 °C were studied. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. - Highlights: • A biodegradable hyaluronic acid hydrogel was crosslinked via aqueous Diels–Alder chemistry. • Dexamethasone was covalently immobilized into the hyaluronic acid hydrogel via aqueous Diels–Alder chemistry. • Dexamethasone could be released from the Diels–Alder hyaluronic acid hydrogel in a controlled fashion

  12. Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

    International Nuclear Information System (INIS)

    Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.; Meer, Berend van; Ward-van Oostwaard, Dorien; Passier, Robert; Tertoolen, Leon G.J.; Mummery, Christine L.; Casini, Simona

    2015-01-01

    One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation. - Highlights: • Dexamethasone accelerates Ca"2"+ transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I_C_a_,_L and action potential characteristics in hESC-CMs.

  13. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    International Nuclear Information System (INIS)

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

    2012-01-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

  14. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O. [Lab. de Radiobiologie, Service de Radio-Oncologie, CHUV, Lausanne (Switzerland); Knebel Doeberitz, M. von [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Inst. fuer Virusforschung

    1998-02-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [Deutsch] Das Ziel dieser Studie lag darin, die Rolle der HPV-18-Gene E6 und E7 in bezug auf die Strahlenempfindlichkeit von menschlichen Zervixkarzinomzellen zu untersuchen. Wir verwendeten zwei menschliche Zervixkarzinomzellinien, C4-1 und SW 756, in welchen die Expression der viralen Gene HPV 18 E6 und E7 mit Dexamethason moduliert werden kann: In C4-1 bewirkt die Behandlung mit Dexamethason eine Erhoehung der Expression dieser Gene, in SW 756 eine Verminderung. Die Wirkung auf die Wachstumsfaehigkeit der Zellen und auf die Wachstumshemmung durch die Bestrahlung wurde unter Verwendung eines klonogenen Assays bestimmt. Dexamethason bewirkte eine erhoehte Wachstumsfaehigkeit der C4-1 Zellen, ohne die Wachstumsfaehigkeit der SW-756-Zellen zu beeinflussen, wie schon frueher beschrieben. Die Resistenz beider Zellinien gegenueber Bestrahlung wurde erhoeht. Somit besteht in den C4-1-Zellen eine Korrelation der Expression der viralen Gene mit der Zunahme der Strahlenresistenz, wogegen in den SW-756-Zellen die Abnahme der Expression im Gegensatz zu

  15. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    Energy Technology Data Exchange (ETDEWEB)

    Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: David.Ammar@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: Chapla.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: Puneet.Tyagi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: Uday.Kompella@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: Robert.Enzenauer@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: Mark.Petrash@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)

    2012-10-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

  16. β-Hydroxy-β-methylbutyrate (HMB normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    María D Girón

    Full Text Available Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

  17. β-Hydroxy-β-methylbutyrate (HMB) normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

    Science.gov (United States)

    Girón, María D; Vílchez, Jose D; Shreeram, Sathyavageeswaran; Salto, Rafael; Manzano, Manuel; Cabrera, Elena; Campos, Nefertiti; Edens, Neile K; Rueda, Ricardo; López-Pedrosa, Jose M

    2015-01-01

    Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

  18. Time-dependent pharmacokinetics of dexamethasone and its efficacy in human breast cancer xenograft mice: a semi-mechanism-based pharmacokinetic/pharmacodynamic model.

    Science.gov (United States)

    Li, Jian; Chen, Rong; Yao, Qing-Yu; Liu, Sheng-Jun; Tian, Xiu-Yun; Hao, Chun-Yi; Lu, Wei; Zhou, Tian-Yan

    2018-03-01

    Dexamethasone (DEX) is the substrate of CYP3A. However, the activity of CYP3A could be induced by DEX when DEX was persistently administered, resulting in auto-induction and time-dependent pharmacokinetics (pharmacokinetics with time-dependent clearance) of DEX. In this study we investigated the pharmacokinetic profiles of DEX after single or multiple doses in human breast cancer xenograft nude mice and established a semi-mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for characterizing the time-dependent PK of DEX as well as its anti-cancer effect. The mice were orally given a single or multiple doses (8 mg/kg) of DEX, and the plasma concentrations of DEX were assessed using LC-MS/MS. Tumor volumes were recorded daily. Based on the experimental data, a two-compartment model with first order absorption and time-dependent clearance was established, and the time-dependence of clearance was modeled by a sigmoid E max equation. Moreover, a semi-mechanism-based PK/PD model was developed, in which the auto-induction effect of DEX on its metabolizing enzyme CYP3A was integrated and drug potency was described using an E max equation. The PK/PD model was further used to predict the drug efficacy when the auto-induction effect was or was not considered, which further revealed the necessity of adding the auto-induction effect into the final PK/PD model. This study established a semi-mechanism-based PK/PD model for characterizing the time-dependent pharmacokinetics of DEX and its anti-cancer effect in breast cancer xenograft mice. The model may serve as a reference for DEX dose adjustments or optimization in future preclinical or clinical studies.

  19. Differential effects of rapamycin and dexamethasone in mouse models of established allergic asthma.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Mushaben

    Full Text Available The mammalian target of rapamycin (mTOR plays an important role in cell growth/differentiation, integrating environmental cues, and regulating immune responses. Our lab previously demonstrated that inhibition of mTOR with rapamycin prevented house dust mite (HDM-induced allergic asthma in mice. Here, we utilized two treatment protocols to investigate whether rapamycin, compared to the steroid, dexamethasone, could inhibit allergic responses during the later stages of the disease process, namely allergen re-exposure and/or during progression of chronic allergic disease. In protocol 1, BALB/c mice were sensitized to HDM (three i.p. injections and administered two intranasal HDM exposures. After 6 weeks of rest/recovery, mice were re-exposed to HDM while being treated with rapamycin or dexamethasone. In protocol 2, mice were exposed to HDM for 3 or 6 weeks and treated with rapamycin or dexamethasone during weeks 4-6. Characteristic features of allergic asthma, including IgE, goblet cells, airway hyperreactivity (AHR, inflammatory cells, cytokines/chemokines, and T cell responses were assessed. In protocol 1, both rapamycin and dexamethasone suppressed goblet cells and total CD4(+ T cells including activated, effector, and regulatory T cells in the lung tissue, with no effect on AHR or total inflammatory cell numbers in the bronchoalveolar lavage fluid. Rapamycin also suppressed IgE, although IL-4 and eotaxin 1 levels were augmented. In protocol 2, both drugs suppressed total CD4(+ T cells, including activated, effector, and regulatory T cells and IgE levels. IL-4, eotaxin, and inflammatory cell numbers were increased after rapamycin and no effect on AHR was observed. Dexamethasone suppressed inflammatory cell numbers, especially eosinophils, but had limited effects on AHR. We conclude that while mTOR signaling is critical during the early phases of allergic asthma, its role is much more limited once disease is established.

  20. Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles.

    Science.gov (United States)

    de Wit, R.; van den Berg, H.; Burghouts, J.; Nortier, J.; Slee, P.; Rodenburg, C.; Keizer, J.; Fonteyn, M.; Verweij, J.; Wils, J.

    1998-01-01

    We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase. PMID:9652766

  1. Removal of dexamethasone from aqueous solution and hospital wastewater by electrocoagulation

    International Nuclear Information System (INIS)

    Arsand, Daniel R.; Kümmerer, Klaus; Martins, Ayrton F.

    2013-01-01

    This study is concerned with the removal of the anti-inflammatory dexamethasone from aqueous solution and hospital wastewater by electrocoagulation. The variation of the toxicity during the electrocoagulation was also studied through experiments that were designed and optimized by means of response surface methodology. The coagulation efficiency was evaluated by measuring the dexamethasone concentration by high performance liquid chromatography coupled to a diode array detector. In addition, variation was evaluated through a Vibrio fischeri test. The results showed an increase in the removal of dexamethasone (up to 38.1%) with a rise of the current applied and a decrease of the inter-electrode distance, in aqueous solutions. The application to hospital effluent showed similar results for the removal of dexamethasone. The main effect of the electrocoagulation was that it removed colloids and reduced the organic load of the hospital wastewater. Regarding the current applied, the calculated energy efficiency was 100%. Without pH adjustment of the aqueous solution or hospital wastewater, the residual aluminum concentration always remained lower than 10 mg L −1 , and, with adjustment (to pH 6.5), lower than 0.30 mg L −1 , at the final stage. No toxicity variation was observed during the electrocoagulation process in aqueous solution, either in the presence or absence of dexamethasone. - Highlights: ► Removal of DEX and organic load from aqueous solution and hospital wastewater by EC ► Evaluation of the toxicity during the removal of DEX by EC ► Suggestion of the EC process as a pretreatment for subsequent processes

  2. Removal of dexamethasone from aqueous solution and hospital wastewater by electrocoagulation

    Energy Technology Data Exchange (ETDEWEB)

    Arsand, Daniel R., E-mail: danielarsand@pelotas.ifsul.edu.br [Chemistry Department, Federal University of Santa Maria, RS (Brazil); Kümmerer, Klaus, E-mail: klaus.kuemmerer@leuphana.de [Institute for Environmental Chemistry, Leuphana University Lüneburg (Germany); Martins, Ayrton F., E-mail: martins@quimica.ufsm.br [Chemistry Department, Federal University of Santa Maria, RS (Brazil)

    2013-01-15

    This study is concerned with the removal of the anti-inflammatory dexamethasone from aqueous solution and hospital wastewater by electrocoagulation. The variation of the toxicity during the electrocoagulation was also studied through experiments that were designed and optimized by means of response surface methodology. The coagulation efficiency was evaluated by measuring the dexamethasone concentration by high performance liquid chromatography coupled to a diode array detector. In addition, variation was evaluated through a Vibrio fischeri test. The results showed an increase in the removal of dexamethasone (up to 38.1%) with a rise of the current applied and a decrease of the inter-electrode distance, in aqueous solutions. The application to hospital effluent showed similar results for the removal of dexamethasone. The main effect of the electrocoagulation was that it removed colloids and reduced the organic load of the hospital wastewater. Regarding the current applied, the calculated energy efficiency was 100%. Without pH adjustment of the aqueous solution or hospital wastewater, the residual aluminum concentration always remained lower than 10 mg L{sup −1}, and, with adjustment (to pH 6.5), lower than 0.30 mg L{sup −1}, at the final stage. No toxicity variation was observed during the electrocoagulation process in aqueous solution, either in the presence or absence of dexamethasone. - Highlights: ► Removal of DEX and organic load from aqueous solution and hospital wastewater by EC ► Evaluation of the toxicity during the removal of DEX by EC ► Suggestion of the EC process as a pretreatment for subsequent processes.

  3. Impairment of wound healing after operative treatment of mandibular fractures, and the influence of dexamethasone.

    Science.gov (United States)

    Snäll, Johanna; Kormi, Eeva; Lindqvist, Christian; Suominen, Anna Liisa; Mesimäki, Karri; Törnwall, Jyrki; Thorén, Hanna

    2013-12-01

    Our aim was to clarify the incidence of impaired wound healing after open reduction and ostheosynthesis of mandibular fractures, and to find out whether the use of dexamethasone during the operation increased the risk. Patients were drawn from a larger group of healthy adult dentate patients who had participated in a single-blind, randomised study, the aim of which was to clarify the benefits of operative dexamethasone after treatment of facial fractures. The present analysis comprised 41 patients who had had open reduction and fixation of mandibular fractures with titanium miniplates and monocortical screws through one or 2 intraoral approaches. The outcome variable was impaired healing of the wound. The primary predictive variable was the perioperative use of dexamethasone; other potential predictive variables were age, sex, smoking habit, type of fracture, delay in treatment, and duration of operation. Wound healing was impaired in 13/41 patients (32%) (13/53 of all fractures). The incidence among patients who were given dexamethasone and those who were not did not differ significantly. Only age over 25 was significantly associated with delayed healing (p=0.02). The use of dexamethasone 30 mg perioperatively did not significantly increase the risk of impaired wound healing in healthy patients with clinically uninfected mandibular fractures fixed with titanium miniplates through an intraoral approach. Older age is a significant predictor of impaired healing, which emphasises the importance of thorough anti-infective care in these patients during and after the operation. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  4. The effects of dexamethasone on post-asphyxial cerebral oxygenation in the preterm fetal sheep

    Science.gov (United States)

    Lear, Christopher A; Koome, Miriam E; Davidson, Joanne O; Drury, Paul P; Quaedackers, Josine S; Galinsky, Robert; Gunn, Alistair J; Bennet, Laura

    2014-01-01

    Exposure to clinical doses of the glucocorticoid dexamethasone increases brain activity and causes seizures in normoxic preterm fetal sheep without causing brain injury. In contrast, the same treatment after asphyxia increased brain injury. We hypothesised that increased injury was in part mediated by a mismatch between oxygen demand and oxygen supply. In preterm fetal sheep at 0.7 gestation we measured cerebral oxygenation using near-infrared spectroscopy, electroencephalographic (EEG) activity, and carotid blood flow (CaBF) from 24 h before until 72 h after asphyxia induced by 25 min of umbilical cord occlusion. Ewes received dexamethasone intramuscularly (12 mg 3 ml–1) or saline 15 min after the end of asphyxia. Fetuses were studied for 3 days after occlusion. During the first 6 h of recovery after asphyxia, dexamethasone treatment was associated with a significantly greater fall in CaBF (P < 0.05), increased carotid vascular resistance (P < 0.001) and a greater fall in cerebral oxygenation as measured by the difference between oxygenated and deoxygenated haemoglobin (delta haemoglobin; P < 0.05). EEG activity was similarly suppressed in both groups. From 6 to 10 h onward, dexamethasone treatment was associated with a return of CaBF to saline control levels, increased EEG power (P < 0.005), greater epileptiform transient activity (P < 0.001), increased oxidised cytochrome oxidase (P < 0.05) and an attenuated increase in [delta haemoglobin] (P < 0.05). In conclusion, dexamethasone treatment after asphyxia is associated with greater hypoperfusion in the critical latent phase, leading to impaired intracerebral oxygenation that may exacerbate neural injury after asphyxia. PMID:25384775

  5. Dexamethasone and sodium carboxymethyl cellulose prevent postoperative intraperitoneal adhesions in rats

    Directory of Open Access Journals (Sweden)

    X.H. Du

    2015-04-01

    Full Text Available We aimed to evaluate the effects of the barrier agent sodium carboxymethyl cellulose (SCMC with and without dexamethasone for the prevention of postoperative adhesion formation in a rat model of postoperative peritoneal adhesion. A total of 160 three-month old male and female Wistar rats underwent a laparotomy, and adhesions were induced by ileocecal abrasion. Rats were randomly assigned to 4 groups (n=40 each: group A, untreated; group B, treated with SCMC only; group C1, treated with SCMC + 3 mg dexamethasone, and group C2, treated with SCMC + 8 mg dexamethasone. After 12 days, adhesion formation and histopathological changes were compared. In groups A, B, C1, and C2, the mortality rates were 10, 5, 5, and 5%, respectively. In groups C1 and C2, the adhesions were filmy and easy to dissect and were milder compared with those in groups A and B. The total adhesion score in group C1 (3.38±0.49 was significantly lower than that of group B (6.01±0.57; P<0.01 or group A (8.01±0.67; P<0.05. There was no significant difference in adhesion formation between groups C1 and C2. Compared with groups A and B, groups C1 and C2 exhibited milder histopathological changes. SCMC in combination with dexamethasone can prevent adhesion formation and is a better barrier agent than SCMC alone. The safety and feasibility of SCMC in combination with dexamethasone to prevent adhesion formation after abdominal surgery warrants further clinical study.

  6. Can short-term administration of dexamethasone abrogate radiation-induced acute cytokine gene response in lung and modify subsequent molecular responses?

    International Nuclear Information System (INIS)

    Hong, J.-H.; Chiang, C.-S.; Tsao, C.-Y.; Lin, P.-Y.; Wu, C.-J.; McBride, William H.

    2001-01-01

    Purpose: To investigate the effects of short-term administration of dexamethasone (DEX) on radiation-induced responses in the mouse lung, focusing on expression of pro-inflammatory cytokine and related genes. Methods and Materials: At indicated times after thoracic irradiation and/or drug treatment, mRNA expression levels of cytokines (mTNF-α, mIL-1α, mIL-1β, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-γ) and related genes in the lungs of C3H/HeN mice were measured by RNase protection assay. Results: Radiation-induced pro-inflammatory cytokine mRNA expression levels in lung peak at 6 h after thoracic irradiation. DEX (5 mg/kg) suppresses both basal cytokine mRNA levels and this early response when given immediately after irradiation. However, by 24 h, in mice treated with DEX alone or DEX plus radiation, there was a strong rebound effect that lasted up to 3 days. Modification of the early radiation-induced response by DEX did not change the second wave of cytokine gene expression in the lung that occurs at 1 to 2 weeks, suggesting that early cytokine gene induction might not determine subsequent molecular events. A single dose of DEX attenuated, but did not completely suppress, increases in cytokine mRNA levels induced by lipopolysaccharide (2.5 mg/kg) treatment, but, unlike with radiation, no significant rebound effect was seen. Five days of dexamethasone treatment in the pneumonitic phase also inhibited pro-inflammatory cytokine gene expression and, again, there was a rebound effect after withdrawal of the drug. Conclusions: Our findings suggest that short-term use of dexamethasone can temporarily suppress radiation-induced pro-inflammatory cytokine gene expression, but there may be a rebound after drug withdrawal and the drug does little to change the essence and course of the pneumonitic process

  7. Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Weiping, E-mail: weiping.qin@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States); Cardozo, Christopher, E-mail: Chris.Cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States)

    2010-12-17

    Research highlights: {yields} In rat gastrocnemius muscle, dexamethasone reduced PGC-1{alpha} cellular and nuclear levels without altering mRNA levels for this factor. {yields} Dexamethasone reduced phosphorylating of p38 MAPK, which stabilizes PGC-1{alpha} and promotes its nuclear entry. {yields} Co-administration of testosterone with dexamethasone increased cellular and nuclear levels of PGC-1{alpha} protein without changing its mRNA levels. {yields} Co-administration of testosterone restored p38 MAPK levels to those of controls. -- Abstract: Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and reduced protein synthesis, associated with increased expression of two muscle-specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein synthesis, REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC-1{alpha} has been shown to attenuate many forms of muscle atrophy and to repress FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced muscle atrophy can be prevented by testosterone, which blocks up-regulation by dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle atrophy was used to further characterize effects of testosterone to abrogate adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to determine how these agents affect PGC-1{alpha}, and its upstream activators, p38 MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and nuclear protein. Dexamethasone reduced total and nuclear PGC-1{alpha} protein levels in the gastrocnemius; co-administration of testosterone with dexamethasone increased total and nuclear PGC-1{alpha} levels above those present in untreated controls. Testosterone blocked dexamethasone-induced decreases in activity of p38 MAPK in the gastrocnemius

  8. Urofollitropin and ovulation induction

    NARCIS (Netherlands)

    van Wely, Madelon; Yding Andersen, Claus; Bayram, Neriman; van der Veen, Fulco

    2005-01-01

    Anovulation is a common cause of female infertility. Treatment for women with anovulation is aimed at induction of ovulation. Ovulation induction with follicle-stimulating hormone (FSH) is indicated in women with WHO type II anovulation in whom treatment with clomifene citrate (clomifene) has

  9. Inductance loop and partial

    CERN Document Server

    Paul, Clayton R

    2010-01-01

    "Inductance is an unprecedented text, thoroughly discussing "loop" inductance as well as the increasingly important "partial" inductance. These concepts and their proper calculation are crucial in designing modern high-speed digital systems. World-renowned leader in electromagnetics Clayton Paul provides the knowledge and tools necessary to understand and calculate inductance." "With the present and increasing emphasis on high-speed digital systems and high-frequency analog systems, it is imperative that system designers develop an intimate understanding of the concepts and methods in this book. Inductance is a much-needed textbook designed for senior and graduate-level engineering students, as well as a hands-on guide for working engineers and professionals engaged in the design of high-speed digital and high-frequency analog systems."--Jacket.

  10. Half Bridge Inductive Heater

    Directory of Open Access Journals (Sweden)

    Zoltán GERMÁN-SALLÓ

    2015-12-01

    Full Text Available Induction heating performs contactless, efficient and fast heating of conductive materials, therefore became one of the preferred heating procedure in industrial, domestic and medical applications. During induction heating the high-frequency alternating currents that heat the material are induced by means of electromagnetic induction. The material to be heated is placed inside the time-varying magnetic field generated by applying a highfrequency alternating current to an induction coil. The alternating electromagnetic field induces eddy currents in the workpiece, resulting resistive losses, which then heat the material. This paper describes the design of a power electronic converter circuit for induction heating equipment and presents the obtained results. The realized circuit is a low power half bridge resonant inverter which uses power MOS transistors and adequate driver circuits.

  11. A New Technique for Quantitative Determination of Dexamethasone in Pharmaceutical and Biological Samples Using Kinetic Spectrophotometric Method

    Directory of Open Access Journals (Sweden)

    Ali Mohammad Akhoundi-Khalafi

    2015-01-01

    Full Text Available Dexamethasone is a type of steroidal medications that is prescribed in many cases. In this study, a new reaction system using kinetic spectrophotometric method for quantitative determination of dexamethasone is proposed. The method is based on the catalytic effect of dexamethasone on the oxidation of Orange G by bromate in acidic media. The change in absorbance as a criterion of the oxidation reaction progress was followed spectrophotometrically. To obtain the maximum sensitivity, the effective reaction variables were optimized. Under optimized experimental conditions, calibration graph was linear over the range 0.2–54.0 mg L−1. The calculated detection limit (3sb/m was 0.14 mg L−1 for six replicate determinations of blank signal. The interfering effect of various species was also investigated. The present method was successfully applied for the determination of dexamethasone in pharmaceutical and biological samples satisfactorily.

  12. Effects of antenatal dexamethasone administration on fetal and uteroplacental Doppler waveforms in women at risk for spontaneous preterm birth

    Directory of Open Access Journals (Sweden)

    Elwani Elsnosy

    2017-03-01

    Conclusion: Maternal dexamethasone administration to pregnant women at risk of preterm labor improves the blood flow of the maternal uterine artery, fetal MCA, descending aorta and umbilical artery 24 h after its administration.

  13. Mechanisms of dexamethasone-mediated inhibition of Toll-like receptor signaling induced by Neisseria meningitidis and Streptococcus pneumoniae

    DEFF Research Database (Denmark)

    Mogensen, Trine; Berg, Randi S; Paludan, Søren R

    2008-01-01

    Excessive inflammation contributes to the pathogenesis of bacterial meningitis, which remains a serious disease despite treatment with antibiotics. Therefore, anti-inflammatory drugs have important therapeutic potential, and clinical trials have revealed that early treatment with dexamethasone...

  14. Compatibility and stability of aloxi (palonosetron hydrochloride) admixed with dexamethasone sodium phosphate.

    Science.gov (United States)

    Trissel, Lawrence A; Zhang, Yanping

    2004-01-01

    The purpose of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 0.25 mg admixed with dexamethasone (as sodium phophate) 10 mg or 20 mg in 5% dextrose injection or 0.9% sodium chloride injection in polyvinylchloride minibags, and also admixed with dexamethasone (as sodium phosphate) 3.3 mg in 5% dextrose injection or 0.9% sodium chloride injection in polypropylene syringes, at 4 deg C stored in the dark for 14 days, and at 23 deg C exposed to normal laboratory fluorescent light over 48 hours. Test samples of palonosetron hydrochloride 5 micrograms/mL with dexamethasone (as sodium phosphate) 0.2 mg/mL and also 0.4 mg/mL were prepared in polyvinylchloride minibags of each infusion solution. Additionally, palonosetron hydrochloride 25 micrograms/mL with dexamethasone (as sodium phosphate) 0.33 mg/mL in each infusion solution were prepared as 10 mL of test solution in 20-mL polypropylene syringes. Evaluations for physical and chemical stability were performed on samples taken initially and after 1, 3, 7 and 14 days of storage at 4 deg C and after 1, 4, 24 and 48 hours at 23 deg C. Physical stability was assessed using visual observation in normal room light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated by using a stability-indicating high-performance liquid chromatographic analytical technique. All samples were physically compatible throughout the study. The solutions remained clear and showed little or no change in particulate burden and haze level. Additionally, little or no loss of palonosetron hydrochloride and dexamethasone occurred in any of the samples at either temperature throughout the entire study period. Admixtures of palonosetron hydrochloride with dexamethasone sodium phosphate in 5% dextrose injection or in 0.9% sodium chloride injection packaged in polyvinylchloride minibags or in

  15. Longstanding refractory pseudophakic cystoid macular edema resolved using intravitreal 0.7 mg dexamethasone implants

    Directory of Open Access Journals (Sweden)

    Brynskov T

    2013-06-01

    Full Text Available Troels Brynskov,1,2 Caroline Schmidt Laugesen,1 Jakob Halborg,1 Henrik Kemp,1 Torben Lykke Sørensen1,21Department of Ophthalmology, Copenhagen University Hospital Roskilde, Roskilde, Denmark; 2Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkBackground: Refractory pseudophakic cystoid macular edema (PCME following cataract surgery has long posed a challenge to clinicians, but intravitreal injections with a sustained delivery 0.7 mg dexamethasone implant has emerged as a promising therapy for this condition.Objective: To present a case of longstanding and refractory PCME with complete remission through 189 days of follow-up after two successive injections with intravitreal dexamethasone implants.Case report: A 59-year-old male had experienced metamorphopsia for approximately 4 years and had been diagnosed with PCME 15 months earlier. Since the time of the diagnosis, the condition had been refractory to both subtenon triamcinolone acetonide and a total of five injections with intravitreal ranibizumab. After the last injection with ranibizumab, central subfield mean thickness was 640 µm, and the best corrected visual acuity was 78 Early Treatment Diabetic Retinopathy Study letters. Following an intravitreal injection with a dexamethasone implant, the macular edema resolved at the next follow-up. The macular edema returned 187 days after the first injection and was treated with another intravitreal dexamethasone implant. Again, the macular edema subsided completely, and best corrected visual acuity improved to 84 Early Treatment Diabetic Retinopathy Study letters, a condition which was maintained through an additional 189 days of follow-up.Conclusion: Chronic PCME is traditionally a difficult condition to treat, but we are encouraged by the optimal response experienced with intravitreal sustained release dexamethasone implants in our patient whose longstanding PCME had been refractory to previous treatments with both

  16. Review of induction LINACS

    International Nuclear Information System (INIS)

    Faltens, A.; Keefe, D.

    1981-10-01

    There has been a recent upsurge of activity in the field of induction linacs, with several new machines becoming operational and others in the design stages. The performance levels of electron machines have reached 10's of kiloamps of current and will soon reach 10's of MeV's of energy. Acceleration of ion current has been demonstrated, and the study of a 10 GeV heavy ion induction linac for ICF continues. The operating principles of induction linacs are reviewed with the emphasis on design choices which are important for increasing the maximum beam currents

  17. Review of induction linacs

    International Nuclear Information System (INIS)

    Faltens, A.; Keefe, D.

    1982-01-01

    There has been a recent upsurge of activity in the field of induction linacs, with several new machines becoming operational and others in the design stages. The performance levels of electron machines have reached 10's of kiloamps of current and will soon reach 10's of MeV's of energy. Acceleration of several kiloamps of ion current has been demonstrated, and the study of a 10 GeV heavy ion induction linac for ICF continues. The operating principles of induction linacs are reviewed with the emphasis on design choices which are important for increasing the maximum beam currents

  18. Properties of inductive reasoning.

    Science.gov (United States)

    Heit, E

    2000-12-01

    This paper reviews the main psychological phenomena of inductive reasoning, covering 25 years of experimental and model-based research, in particular addressing four questions. First, what makes a case or event generalizable to other cases? Second, what makes a set of cases generalizable? Third, what makes a property or predicate projectable? Fourth, how do psychological models of induction address these results? The key results in inductive reasoning are outlined, and several recent models, including a new Bayesian account, are evaluated with respect to these results. In addition, future directions for experimental and model-based work are proposed.

  19. Granisetron plus dexamethasone for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: A meta-analysis

    OpenAIRE

    Zhu, Min; Zhou, Chengmao; Huang, Bing; Ruan, Lin; Liang, Rui

    2017-01-01

    Objective This study was designed to compare the effectiveness of granisetron plus dexamethasone for preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic surgery. Methods We searched the literature in the Cochrane Library, PubMed, EMBASE, and CNKI. Results In total, 11 randomized controlled trials were enrolled in this analysis. The meta-analysis showed that granisetron in combination with dexamethasone was significantly more effective than granisetron alone...

  20. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    OpenAIRE

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In ...

  1. The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells

    International Nuclear Information System (INIS)

    Medrado, G C B; Machado, C B; Valerio, P; Sanches, M D; Goes, A M

    2006-01-01

    Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering

  2. The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Medrado, G C B [Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Machado, C B [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil); Valerio, P [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil); Sanches, M D [Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Goes, A M [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil)

    2006-09-15

    Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering.

  3. Dexamethasone-(C21-phosphoramide)-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2016-01-01

    Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively "target" delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR)-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide)-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549) known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide)-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10(-9) M and 10(-5) M. Rapid increases in

  4. Induction melter apparatus

    Science.gov (United States)

    Roach, Jay A [Idaho Falls, ID; Richardson, John G [Idaho Falls, ID; Raivo, Brian D [Idaho Falls, ID; Soelberg, Nicholas R [Idaho Falls, ID

    2008-06-17

    Apparatus and methods of operation are provided for a cold-crucible-induction melter for vitrifying waste wherein a single induction power supply may be used to effect a selected thermal distribution by independently energizing at least two inductors. Also, a bottom drain assembly may be heated by an inductor and may include an electrically resistive heater. The bottom drain assembly may be cooled to solidify molten material passing therethrough to prevent discharge of molten material therefrom. Configurations are provided wherein the induction flux skin depth substantially corresponds with the central longitudinal axis of the crucible. Further, the drain tube may be positioned within the induction flux skin depth in relation to material within the crucible or may be substantially aligned with a direction of flow of molten material within the crucible. An improved head design including four shells forming thermal radiation shields and at least two gas-cooled plenums is also disclosed.

  5. Linear induction accelerator

    Science.gov (United States)

    Buttram, M.T.; Ginn, J.W.

    1988-06-21

    A linear induction accelerator includes a plurality of adder cavities arranged in a series and provided in a structure which is evacuated so that a vacuum inductance is provided between each adder cavity and the structure. An energy storage system for the adder cavities includes a pulsed current source and a respective plurality of bipolar converting networks connected thereto. The bipolar high-voltage, high-repetition-rate square pulse train sets and resets the cavities. 4 figs.

  6. Linear induction accelerators

    International Nuclear Information System (INIS)

    Briggs, R.J.

    1986-06-01

    The development of linear induction accelerators has been motivated by applications requiring high-pulsed currents of charged particles at voltages exceeding the capability of single-stage, diode-type accelerators and at currents too high for rf accelerators. In principle, one can accelerate charged particles to arbitrarily high voltages using a multi-stage induction machine, but the 50-MeV, 10-kA Advanced Test Accelerator (ATA) at LLNL is the highest voltage machine in existence at this time. The advent of magnetic pulse power systems makes sustained operation at high-repetition rates practical, and this capability for high-average power is very likely to open up many new applications of induction machines in the future. This paper surveys the US induction linac technology with primary emphasis on electron machines. A simplified description of how induction machines couple energy to the electron beam is given, to illustrate many of the general issues that bound the design space of induction linacs

  7. Development and characterization of nanoparticulate formulation of a water soluble prodrug of dexamethasone by HIP complexation.

    Science.gov (United States)

    Gaudana, Ripal; Parenky, Ashwin; Vaishya, Ravi; Samanta, Swapan K; Mitra, Ashim K

    2011-01-01

    The objective of this study was to develop and characterize a nanoparticulate-based sustained release formulation of a water soluble dipeptide prodrug of dexamethasone, valine-valine-dexamethasone (VVD). Being hydrophilic in nature, it readily leaches out in the external aqueous medium and hence partitions poorly into the polymeric matrix resulting in minimal entrapment in nanoparticles. Hence, hydrophobic ion pairing (HIP) complexation of the prodrug was employed with dextran sulphate as a complexing polymer. A novel, solid in oil in water emulsion method was employed to encapsulate the prodrug in HIP complex form in poly(lactic-co-glycolic acid) matrix. Nanoparticles were characterized with respect to size, zeta potential, crystallinity of entrapped drug and surface morphology. A significant enhancement in the entrapment of the prodrug in nanoparticles was achieved. Finally, a simple yet novel method was developed which can also be applicable to encapsulate other charged hydrophilic molecules, such as peptides and proteins.

  8. Linezolid and dexamethasone experience in a serious case of listeria rhombencephalitis.

    Science.gov (United States)

    Yılmaz, Pakize Ö; Mutlu, Nevzat M; Sertçelik, Ahmet; Baştuğ, Aliye; Doğu, Cihangir; Kışlak, Sümeyye

    2016-01-01

    Listeria rhombencephalitis is a rare cause of brain stem encephalitis. We report a case with a history of immunosupressive therapy due to Takayasu's arteritis that was treated with corticosteroids and linezolid for Listeria rhombencephalitis. A 63-year-old woman was admitted to the hospital with fever, headache, nausea, and vomiting. The patient's body temperature was 38°C, and she had a stiff neck. Listeria monocytogenes was isolated from the cerebrospinal fluid (CSF), and penicillin G and gentamicin treatment was initiated. Linezolid and dexamethasone were added. Due to hematuria and thrombocytopenia, the linezolid was discontinued. In immunocompromised patients with CNS infections, Listeria rhombencephalitis should be suspected. Linezolid can be used in combination with dexamethasone. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  9. In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

    International Nuclear Information System (INIS)

    Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

    1988-01-01

    Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

  10. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

    Science.gov (United States)

    Nishiwaki, Satoshi; Nakayama, Takayuki; Murata, Makoto; Nishida, Tetsuya; Terakura, Seitaro; Saito, Shigeki; Kato, Tomonori; Mizuno, Hiroki; Imahashi, Nobuhiko; Seto, Aika; Ozawa, Yukiyasu; Miyamura, Koichi; Ito, Masafumi; Takeshita, Kyosuke; Kato, Hidefumi; Toyokuni, Shinya; Nagao, Keisuke; Ueda, Ryuzo; Naoe, Tomoki

    2014-01-01

    Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

  11. In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

    Energy Technology Data Exchange (ETDEWEB)

    Hotchkiss, J A; Portereiko, J V; Harkema, J R

    1988-12-01

    Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

  12. Peptic ulcer disease and other complications in patients receiving dexamethasone palliation for brain metastasis

    International Nuclear Information System (INIS)

    Penzner, R.D.; Lipsett, J.A.

    1982-01-01

    A retrospective analysis was done of 106 patients who received radiation therapy for brain metastasis. Dexamethasone therapy was instituted in 97 patients. Peptic ulcer disease developed in 5 of 89 patients (5.6 percent) who received a dosage of at least 12 mg a day, but did not occur in patients who received a lower dose or in those who did not receive steroids. The interval between institution of dexamethasone therapy and the development of peptic ulcer disease ranged from three to nine weeks. Two patients had perforated ulcers, one of whom required surgical resection. Peptic ulcer disease contributed to the general deterioration and death of three of the five patients. Overall, in 14 of the 89 patients (15.7 percent) a complication of steroid therapy developed in the form of peptic ulcer disease, steroid myopathy or diabetes mellitus (or a combination of these)

  13. Emergency department treatment of viral gastritis using intravenous ondansetron or dexamethasone in children.

    Science.gov (United States)

    Stork, Christine M; Brown, Kathleen M; Reilly, Tracey H; Secreti, LaLaina; Brown, Lawrence H

    2006-10-01

    To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and analysis of variance, with p hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.

  14. Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits

    OpenAIRE

    Sun, Hongfan

    2009-01-01

    Linhua Zhang1, Yue Li2, Chao Zhang1, Yusheng Wang2, Cunxian Song11Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China; 2Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaAbstract: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX)-loaded poly(lactic acid–co-glycolic acid) ...

  15. Low-Dose Dexamethasone Therapy from Infancy of Virilizing Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Scott A. Rivkees

    2009-01-01

    Full Text Available Objective. To assess the growth and control of adrenal androgen secretion in children with virilizing congenital adrenal hyperplasia (CAH treated with dexamethasone. Method. We examined doses used, control of adrenal androgen secretion, and growth and skeletal maturation of 8 children with CAH treated with dexamethasone beginning in infancy. Results. 3 boys and 5 girls with classical CAH (17-hydroxyprogesterone at diagnosis >20,000 ng/dL were treated with dexamethasone beginning at diagnosis (<10 days of age. Patients were also treated with fludrocortisone and sodium chloride. The average initial medication dose was 0.1 mg (0.28±0.015 mg/m2; all doses were given in the morning using a dosing syringe to administer a 0.1 mg/mL elixir. The children were treated for 6.5±2.0 years over which time the change in bone age to chronological age ratio (ΔBA/ΔCA was 0.9±0.06. Most recent height Z' scores were +0.5±0.2, and body mass index (BMI scores were 18±0.2. Late afternoon levels of 17-hydroxyprogesterone, androstenedione, and testosterone were 780±238 ng/dL (23.4±7 nmol/L, 42±10 ng/dL (1.4±0.3 nmol/L, and 11.5±3 ng/dL; (0.4±0.1 nmol/L, respectively. Conclusions. These observations show that low doses of dexamethasone can be used to effectively treat CAH beginning in infancy.

  16. ATM splicing variants as biomarkers for low dose dexamethasone treatment of A-T.

    Science.gov (United States)

    Menotta, Michele; Biagiotti, Sara; Spapperi, Chiara; Orazi, Sara; Rossi, Luigia; Chessa, Luciana; Leuzzi, Vincenzo; D'Agnano, Daniela; Soresina, Annarosa; Micheli, Roberto; Magnani, Mauro

    2017-07-05

    Ataxia Telangiectasia (AT) is a rare incurable genetic disease, caused by biallelic mutations in the Ataxia Telangiectasia-Mutated (ATM) gene. Treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this syndrome. Nevertheless, the molecular mechanism underlying the glucocorticoid action in AT patients is not yet understood. Recently, we have demonstrated that Dexamethasone treatment may partly restore ATM activity in AT lymphoblastoid cells by a new ATM transcript, namely ATMdexa1. In the present study, the new ATMdexa1 transcript was also identified in vivo, specifically in the PMBCs of AT patients treated with intra-erythrocyte Dexamethasone (EryDex). In these patients it was also possible to isolate new "ATMdexa1 variants" originating from canonical and non-canonical splicing, each containing the coding sequence for the ATM kinase domain. The expression of the ATMdexa1 transcript family was directly related to treatment and higher expression levels of the transcript in patients' blood correlated with a positive response to Dexamethasone therapy. Neither untreated AT patients nor untreated healthy volunteers possessed detectable levels of the transcripts. ATMdexa1 transcript expression was found to be elevated 8 days after the drug infusion, while it decreased 21 days after treatment. For the first time, the expression of ATM splicing variants, similar to those previously observed in vitro, has been found in the PBMCs of patients treated with EryDex. These findings show a correlation between the expression of ATMdexa1 transcripts and the clinical response to low dose dexamethasone administration.

  17. Cisplatin-Induced Conditioned Taste Aversion: Attenuation by Dexamethasone but not Zacopride or GR38032F

    Science.gov (United States)

    1992-01-01

    SR2-1 Cisplatin-induced conditioned taste aversion: ateuto by dexamethasone but not zacopride or GR38032F Nm I- Paul C Mele, John R. McDonough, David...to 5-H1’, receptor blockade. 5-HT., receptor antagonists; Zacopridc: GR38032F; Desamethasone: Cisplatin: Taste aversion (conditioned) I. Introductlon...intake) was used as the area known as the chemoreceptor trigger zone (Borri- index of the CTA. son, 1974). Moreover. the findings that rats, ferrets

  18. Efficacy of two regimens of dexamethasone for management of preterm labour: pilot study

    International Nuclear Information System (INIS)

    Rasool, A.; Farooq, U.

    2017-01-01

    Background: Dexamethasone is widely used for prevention of respiratory distress syndrome (RDS), necrotising enterocolitis (NEC) and intra-ventricular haemorrhage (IVH) in preterm babies; decreasing the neonatal mortality rate. There is no consensus on the dose of corticosteroid administered to the mother expected to have a preterm baby. This study is conducted to compare the effectiveness of two popular regimens of dexamethasone administration in decreasing incidence of RDS, necrotizing enterocolitis, IVH and neonatal mortality rate. Methods: Randomized control trial was conducted at Ayub Teaching Hospital, Abbottabad from 1st to 31st August, 2014. Sample size was set at 50. Block randomization was employed in the trial to allocate the patients into corresponding groups 'A' and 'B'. Group A was administered 6mg dexamethasone in 4 doses 12 hours apart and group B was administered 2 doses 12 hours apart. Results: Forty-eight patients participated in the study with 24 patients in each group. Mean age and period gestation of participants were 28.4 years±4.3 SD and 34 weeks±1.9 SD respectively. Four patients in group A gave birth to neonate with RDS compared to two cases in group B. Group B had higher incidence of necrotizing enterocolitis and neonatal mortalities. However, none of these differences observed were statistically significant. No case of IVH was reported in either of the groups. Conclusion: Both the popular regimens of dexamethasone administration are equally effective in decreasing the incidence of neonatal diseases. (author)

  19. The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma

    OpenAIRE

    Hernández-García, Susana; San-Segundo, Laura; González-Méndez, Lorena; Corchete, Luis A; Misiewicz-Krzeminska, Irena; Martín-Sánchez, Montserrat; López-Iglesias, Ana-Alicia; Algarín, Esperanza Macarena; Mogollón, Pedro; Díaz-Tejedor, Andrea; Paíno, Teresa; Tunquist, Brian; Mateos, María-Victoria; Gutiérrez, Norma C; Díaz-Rodriguez, Elena

    2017-01-01

    [EN]Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. The ability of filanesib to enhance the activity of pomali...

  20. Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone.

    Directory of Open Access Journals (Sweden)

    Gabriella Neves Leal Santos Barreto

    2017-03-01

    Full Text Available Bothrops atrox snakes are the leading cause of snake bites in Northern Brazil. The venom of this snake is not included in the antigen pool used to obtain the Bothrops antivenom. There are discrepancies in reports on the effectiveness of this antivenom to treat victims bitten by B. atrox snakes. However, these studies were performed using a pre-incubation of the venom with the antivenom and, thus, did not simulate a true case of envenomation treatment. In addition, the local lesions induced by Bothrops venoms are not well resolved by antivenom therapy. Here, we investigated the efficacy of the Bothrops antivenom in treating the signs and symptoms caused by B. atrox venom in mice and evaluated whether the combination of dexamethasone and antivenom therapy enhanced the healing of local lesions induced by this envenomation. In animals that were administered the antivenom 10 minutes after the envenomation, we observed an important reduction of edema, dermonecrosis, and myonecrosis. When the antivenom was given 45 minutes after the envenomation, the edema and myonecrosis were reduced, and the fibrinogen levels and platelet counts were restored. The groups treated with the combination of antivenom and dexamethasone had an enhanced decrease in edema and a faster recovery of the damaged skeletal muscle. Our results show that Bothrops antivenom effectively treats the envenomation caused by Bothrops atrox and that the use of dexamethasone as an adjunct to the antivenom therapy could be useful to improve the treatment of local symptoms observed in envenomation caused by Bothrops snakes.

  1. Effect of postoperative dexamethasone on pain, emesis and haemorrhage in tonsillectomy by dissection method

    International Nuclear Information System (INIS)

    Khan, K.A.; Faiz, S.B.

    2013-01-01

    Objectives: To compare the effect of postoperative intravenous dose of dexamethasone on morbidity in patients undergoing tonsillectomy. Design: Randomized control trial. Place and Duration of Study: This study was conducted in ENT Department Shaikh Khalifa Bin Zayed Al Nahyan Hospital (CMH) Muzaffarabad from 10th Jan 2010 to 15th Feb 2011. Patients and Methods: After getting informed consent, a total of 60 patients who fulfilled the inclusion criteria were selected and tonsillectomy by dissection method was carried out. They were divided into two groups of 30 each using a random numbers table. Group A received 0.25 mg/kg body weight (maximum 20 mg) of Dexamethasone postoperatively intravenously for 03 days while group B (control group) did not receive any steroid. Results: In group A, 80% patients had mild pain, 16.7% had moderate pain and 3.3% had a severe pain while in group B, 30% patients had mild pain, 6.7% had moderate pain and 63.3% had severe pain (p< 0.05). In group A, 76.7% patients had mild emesis while in group B, 86.7% had moderate emesis (p< 0.05). There was an insignificant difference in secondary hemorrhage. Conclusion: Dexamethasone given postoperatively significantly reduces the morbidity that is pain, episodes of emesis thus early recovery to a normal lifestyle with no effect on secondary hemorrhage in patients undergoing Tonsillectomy by dissection method. (author)

  2. The effect of preoperative dexamethasone on pain 1 year after lumbar disc surgery

    DEFF Research Database (Denmark)

    Nielsen, Rikke Vibeke; Fomsgaard, Jonna; Mathiesen, Ole

    2016-01-01

    discectomy. METHODS: This is a prospective 1-year follow-up on a single-centre, randomized, and blinded trial exploring the analgesic effect of 16 mg IV dexamethasone or placebo after lumbar discectomy. One year follow-up was a written questionnaire including back and leg pain (VAS 0-100 mm), Short Form 36...... survey (SF-36), EuroQol 5D (EQ-5D), OSWESTRY Low Back Pain Questionnaire, duration of sick leave, working capability, contentment with surgical result. RESULTS: Response rate was 71% (55 patients) in the dexamethasone group, 58% (44 patients) in the placebo group. Leg pain (VAS) was significantly lower...... in the placebo group compared to the dexamethasone group: 17 (95% CI 10-26) vs 26 (95% CI 19-33) mm, respectively (mean difference 9 mm (95% CI -1 to 0), (P = 0.03). No difference regarding back pain. The placebo group reported significantly more improvement of leg pain and were significantly more satisfied...

  3. Intraperitoneal Dexamethasone As A New Method for Relieving Postoperative Shoulder Pain after Gynecologic Laparoscopy

    Directory of Open Access Journals (Sweden)

    Zahra Asgari

    2012-01-01

    Full Text Available Background: In this study, we tried to show the efficacy of Intraperitoneal dexamethasoneon relieving shoulder pain after gynecologic laparoscopy.Materials and Methods: In this double-blind randomized clinical trial, 63 patients who werecandidates for gynecologic laparoscopy were included. At the end of the procedure patientsrandomly received 16 mg dexamethasone (n=31 or placebo (n=32 intraperitoneally. Visualanalogue scale (VAS was used for clinical evaluation of pain severity during 24 hours afterlaparoscopy . A physician, who was not aware whether patients were treated with drug or placebo,evaluated the patients.Results: The severity of pain in the dexamethasone group within 0, 2, 4, 8, 12, 24 hoursafter procedure was significantly less than in the placebo group (p<0.001. The averageconsumption of opioids as analgesic/ sedative in the placebo group was more than thedexamethasone group (p=0.025.Conclusion: Findings of this study show that the prescription of 16 mg of dexamethasone(single dose in the peritoneal cavity may significantly reduce the severity of painafter Laparoscopy in comparison with placebo and may decrease the need for narcoticsas pain relief (Registration Number: IRCT201105306640N1.

  4. Bilateral Intravitreal Dexamethasone Implant for Retinitis Pigmentosa-Related Macular Edema

    Directory of Open Access Journals (Sweden)

    Ali Osman Saatci

    2013-03-01

    Full Text Available Purpose: To report the efficacy of intravitreal dexamethasone implant in a patient with retinitis pigmentosa and bilateral cystoid macular edema unresponsive to topical carbonic anhydrase inhibitors. Case Report: A 36-year-old man with bilateral cystoid macular edema associated with retinitis pigmentosa that was unresponsive to topical carbonic anhydrase inhibitors underwent bilateral 0.7-mg intravitreal dexamethasone implants two weeks apart. Spectral domain optical coherence tomography revealed resolution of macular edema one week following each injection in both eyes and his visual acuity improved. However, macular edema recurred two months later in OS and three months later in OD. Second implant was considered for both eyes. No implant-related complication was experienced during the follow-up of seven months. Conclusion: Inflammatory process seems to play a role in retinitis pigmentosa. Intravitreal dexamethasone implant may offer retina specialists a therapeutic option especially in cases unresponsive to other treatment regimens in eyes with retinitis pigmentosa-related macular edema.

  5. Simultaneous RP-HPLC determination of sparfloxacin and dexamethasone in pharmaceutical formulations

    Directory of Open Access Journals (Sweden)

    Syed Naeem Razzaq

    2013-06-01

    Full Text Available The present study describes the development and subsequent validation of simple and accurate stability indicating RP-HPLC method for the determination of sparfloxacin and dexamethasone in pharmaceutical formulations in the presence of their stress-induced degradation products. Both the drugs and their stress-induced degradation products were separated within 10 minutes using C8 column and mixture of methanol and 0.02 M phosphate buffer pH 3.0 (60:40 v/v, respectively as mobile phase at 270 nm using diode array detector. Regression analysis showed linearity in the range of 15-105 µg/mL for sparfloxacin and 5-35 µg/mL for dexamethasone. All the analytes were adequately resolved with acceptable tailing. Peak purity of the two drugs was also greater than 0.9999, showing no co-elution peaks. The developed method was applied for simultaneous determination of sparfloxacin and dexamethasone in pharmaceutical formulations for stability studies.

  6. Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice.

    Science.gov (United States)

    Patel, Sita Sharan; Udayabanu, Malairaman

    2014-03-01

    Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction.

  7. Atrial natriuretic peptide: a possible mediator involved in dexamethasone's inhibition of cell proliferation in multiple myeloma.

    Science.gov (United States)

    Ding, Jiang-Hua; Chang, Yu-Sui

    2012-08-01

    Atrial natriuretic peptide (ANP) has been recognized for several decades for its role of regulating blood pressure. Recently, cumulating evidences show that ANP plays an anticancer role in various solid tumors via blocking the kinase cascade of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well as its receptors (NPR-A and NPR-C) has been identified present in the embryonic stem cell and a wide range of cancer cells. Various lymphoid organs, such as lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM), though the therapies have evolved significantly, is still an incurable disease as B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently, dexamethasone can increase the expression of ANP markedly. Nevertheless, the role of ANP in MM is unclear. Based on these results above, we raise the hypothesis that ANP is involved in mediating dexamethasone's inhibition of proliferation in MM cells, which suggests that ANP may be a potential agent to treat MM. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  8. Fatal Gastrointestinal Hemorrhage in a Young Boy with Newly Diagnosed Metastatic Medulloblastoma on High Dose Dexamethasone

    Directory of Open Access Journals (Sweden)

    Victor Wong

    2014-01-01

    Full Text Available A 10-year-old boy with newly diagnosed metastatic medulloblastoma was placed on high dose dexamethasone and ranitidine prior to surgery. The child underwent subtotal resection and was discharged 5 days postoperatively with an uneventful hospital course on a tapering dose of dexamethasone and ranitidine. Over the next 2 days the patient complained of mild abdominal distension with flatulence, without pain, vomiting, or dysmotility. On follow-up in clinic 5 days after discharge, he had normal vital signs when he suddenly became pale and had loss of consciousness. Emergent computerized tomography of the head showed no acute hemorrhage and complete blood count revealed hemoglobin of 4.2 gm/dL. In spite of maximum resuscitation with copious blood products the patient died. Autopsy revealed evidence of duodenal perforation with intraluminal hemorrhage. This case demonstrates a rare fatal complication of high dose dexamethasone therapy even with concurrent gastrointestinal prophylactic therapy. We provide a review of the limited literature on steroid use in pediatric neurooncology with regard to gastrointestinal bleeding.

  9. Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema

    Directory of Open Access Journals (Sweden)

    Rocío Herrero-Vanrell, Jose Augusto Cardillo

    2011-02-01

    Full Text Available Rocío Herrero-Vanrell1, Jose Augusto Cardillo2, Baruch D Kuppermann31Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain; 2Hospital de Olhos de Araraquara, Araraquara, São Paulo, Brazil; 3Gavin Herbert Eye Institute, University of California, Irvine, CA, USAAbstract: Macular edema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macular edema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex® has enabled more controlled drug release at a stable rate over a long period of time, with a potentially lower rate of adverse events. Clinical studies indicate that this dexamethasone implant is a promising new treatment option for patients with persistent macular edema resulting from retinal vein occlusion, diabetic retinopathy, and uveitis or Irvine-Gass syndrome.Keywords: diabetic retinopathy, macular edema, Ozurdex®, posterior-segment inflammatory disease, retinal vein occlusion, sustained-release dexamethasone implant

  10. Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma

    International Nuclear Information System (INIS)

    Siegel, D S; Richardson, P; Dimopoulos, M; Moreau, P; Mitsiades, C; Weber, D; Houp, J; Gause, C; Vuocolo, S; Eid, J; Graef, T; Anderson, K C

    2014-01-01

    The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1–7 and 15–21, 25 mg lenalidomide on days 1–21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed

  11. Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States.

    Science.gov (United States)

    Jakubowiak, Andrzej J; Houisse, Ivan; Májer, István; Benedict, Ágnes; Campioni, Marco; Panjabi, Sumeet; Ailawadhi, Sikander

    2017-12-01

    We assessed the economic value of carfilzomib 56 mg/m 2 and dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients. Utilities were sourced from the literature and mapped from patient-reported quality of life in ENDEAVOR to estimate quality-adjusted life-years (QALYs) from life-years (LYs). The model predicted an average gain of 1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior treatment; $99,263/QALY in those not transplanted, and discount in bortezomib price. Kd56 is cost-effective for patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial data in the model may limit generalizability; however, SEER registry data mitigates this challenge. Kd56 provides additional value in key subgroups, and remains cost-effective after steep comparator discounts.

  12. The role of adjunctive dexamethasone in the treatment of bacterial meningitis: an updated systematic meta-analysis

    Directory of Open Access Journals (Sweden)

    Shao M

    2016-07-01

    Full Text Available Mei Shao,1 Peng Xu,2 Jun Liu,3 Wenyun Liu,1 Xiujie Wu1 1Department of Neurosurgery, Linyi People’s Hospital, 2Department of Neurosurgery, Linyi Yishui Central Hospital, Linyi, 3Department of Neurosurgery, Binzhou Medical College, Yantai, Shandong, People’s Republic of China Background: Bacterial meningitis is a serious infection in children and adults worldwide, with considerable morbidity, mortality, and severe neurological sequelae. Dexamethasone is often used before antibiotics in cases of this disease, and improves outcomes.Objective: Although several studies have identified the role of adjunctive dexamethasone therapy in the treatment of bacterial meningitis, the results are still inconclusive. The aim of this study was to systematically evaluate the therapeutic and adverse effect of adjunctive dexa­methasone in patients with bacterial meningitis.Materials and methods: Relevant randomized, double-blind, placebo-controlled trials of dexamethasone in bacterial meningitis published between 2000 and 2016 were retrieved from the common electronic databases. The odds ratio (OR and risk ratio (RR with their 95% confidence interval (CI were employed to calculate the effect.Results: A total of ten articles including 2,459 bacterial meningitis patients (1,245 in the dexamethasone group and 1,214 in the placebo group were included in this meta-analysis. Our result found that dexamethasone was not associated with a significant reduction in follow-up mortality (292 of 1,245 on dexamethasone versus 314 of 1,214 on placebo; OR =0.91, 95% CI =0.80–1.03, P=0.14 and severe neurological sequelae (22.4% versus 24.1%, OR =0.84, 95% CI =0.54–1.29, P=0.42. However, dexamethasone seemed to reduce hearing loss among survivors (21.2% versus 26.1%; OR =0.76, 95% CI =0.59–0.98, P=0.03. No significant difference was found between these two groups in adverse events.Conclusion: Our results suggested that adjunctive dexamethasone might not be beneficial in the

  13. The effects of dexamethasone on the Na,K-ATPase activity and pump function of corneal endothelial cells.

    Science.gov (United States)

    Hatou, Shin; Yamada, Masakazu; Mochizuki, Hiroshi; Shiraishi, Atsushi; Joko, Takeshi; Nishida, Teruo

    2009-05-01

    The Na(+)- and K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the possible role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells. Confluent monolayers of mouse corneal endothelial cells were exposed to dexamethasone. ATPase activity of the cells was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate, with Na,K-ATPase activity being defined as the portion of total ATPase activity sensitive to ouabain. Pump function of the cells was measured with the use of an Ussing chamber, with the pump function attributable to Na,K-ATPase activity being defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis was examined to measure the expression of the Na,K-ATPase alpha(1)-subunit. Dexamethasone (1 or 10 microM) increased the Na,K-ATPase activity and pump function of the cultured cells. These effects of dexamethasone were blocked by cycloheximide, a protein synthesis inhibitor. Western blot analysis also indicated that dexamethasone increased the expression of the Na,K-ATPase alpha(1)-subunit, whereas it decreased the expression of the phospho-Na,K-ATPase alpha(1)-subunit. Our results suggest that dexamethasone stimulates Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells is mediated by Na,K-ATPase synthesis and increase in an enzymatic activity by dephosphorylation of Na,K-ATPase alpha(1)-subunits.

  14. Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma.

    Science.gov (United States)

    Chang, Diane T W; Herceg, Michael C; Bilonick, Richard A; Camejo, Larissa; Schuman, Joel S; Noecker, Robert J

    2009-01-01

    To evaluate whether dexamethasone injected intracamerally at the conclusion of surgery can safely and effectively reduce postoperative inflammation and improve surgical outcomes in eyes with and without glaucoma. Retrospective chart review of 176 consecutive eyes from 146 patients receiving uncomplicated phacoemulsification (PE) (n = 118 total, 82 with glaucoma), glaucoma drainage device (GDD) (n = 35), combined PE/GDD (n = 11) and combined PE/endoscopic cyclophotocoagulation (n = 12). Ninety-one eyes from 76 patients were injected with 0.4 mg dexamethasone intracamerally at the conclusion of surgery. All eyes received standard postoperative prednisolone and ketorolac eyedrops. Outcomes were measured for four to eight weeks by subjective complaints, visual acuity (VA), slit-lamp biomicroscopy, intraocular pressure (IOP) and postoperative complications. Dexamethasone significantly reduced the odds of having an increased anterior chamber (AC) cell score after PE (p = 0.0013). Mean AC cell score +/- SD in nonglaucomatous eyes was 1.3 +/- 0.8 in control and 0.8 +/- 0.7 with dexamethasone; scores in glaucomatous eyes were 1.3 +/- 0.7 in control and 0.9 +/- 0.8 with dexamethasone. Treated nonglaucomatous eyes had significantly fewer subjective complaints after PE (22.2% vs 64.7% in control; p = 0.0083). Dexamethasone had no significant effects on VA, corneal changes, IOP one day and one month after surgery, or long-term complications. Intracameral dexamethasone given at the end of cataract surgery significantly reduces postoperative AC cells in eyes with and without glaucoma, and improves subjective reports of recovery in nonglaucomatous eyes. There were no statistically significant risks of IOP elevation or other complications in glaucomatous eyes.

  15. Effect of dexamethasone in low volume supraclavicular brachial plexus block: A double-blinded randomized clinical study

    Directory of Open Access Journals (Sweden)

    Arun Kumar Alarasan

    2016-01-01

    Full Text Available Background and Aims: With the use of ultrasound, a minimal effective volume of 20 ml has been described for supraclavicular brachial plexus block. However achieving a long duration of analgesia with this minimal volume remains a challenge. We aimed to determine the effect of dexamethasone on onset and duration of analgesia in low volume supraclavicular brachial plexus block. Material and Methods: Sixty patients were randomly divided into two groups of 30 each. Group C received saline (2 ml + 20 ml of 0.5% bupivacaine and Group D received dexamethasone (8 mg + 20 ml of 0.5% bupivacaine in supraclavicular brachial plexus block. Hemodynamic variables and visual analog scale (VAS score were noted at regular intervals until 450 min. The onset and duration of sensory and motor block were measured. The incidence of "Halo" around brachial plexus was observed. Student′s t-test and Chi-square test were used for statistical analysis. Results: The onset of sensory and motor block was significantly earlier in dexamethasone group (10.36 ± 1.99 and 12 ± 1.64 minutes compared to control group (12.9 ± 2.23 and 18.03 ± 2.41 minutes. The duration of sensory and motor block was significantly prolonged in dexamethasone group (366 ± 28.11 and 337.33 ± 28.75 minutes compared to control group (242.66 ± 26.38 and 213 ± 26.80 minutes. The VAS score was significantly lower in dexamethasone group after 210 min. "Halo" was present around the brachial plexus in all patients in both the groups. Conclusion: Dexamethasone addition significantly increases the duration of analgesia in patients receiving low volume supraclavicular brachial plexus block. No significant side-effects were seen in patients receiving dexamethasone as an adjunct.

  16. Inductive dielectric analyzer

    International Nuclear Information System (INIS)

    Agranovich, Daniel; Popov, Ivan; Ben Ishai, Paul; Feldman, Yuri; Polygalov, Eugene

    2017-01-01

    One of the approaches to bypass the problem of electrode polarization in dielectric measurements is the free electrode method. The advantage of this technique is that, the probing electric field in the material is not supplied by contact electrodes, but rather by electromagnetic induction. We have designed an inductive dielectric analyzer based on a sensor comprising two concentric toroidal coils. In this work, we present an analytic derivation of the relationship between the impedance measured by the sensor and the complex dielectric permittivity of the sample. The obtained relationship was successfully employed to measure the dielectric permittivity and conductivity of various alcohols and aqueous salt solutions. (paper)

  17. The efficacy of dexamethasone reducing postoperative pain and emesis after total knee arthroplasty: A systematic review and meta-analysis.

    Science.gov (United States)

    Fan, Zhengrui; Ma, Jianxiong; Kuang, Mingjie; Zhang, Lukai; Han, Biao; Yang, Baocheng; Wang, Ying; Ma, Xinlong

    2018-04-01

    Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, Perioperative dexamethasone treatment is still a controversial subject in total knee arthroplasty. Therefore, we write this systematic review and meta-analysis to evaluate the efficacy of dexamethasone on pain and recovery after Total knee Arthroplasty. Embase, Pubmed, and Cochrane Library were comprehensively searched. Randomized controlled trials, cohort studies were included in our meta-analysis. Eight studies that compared dexamethasone groups with placebo groups were included in our meta-analysis. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Randomized controlled trials were included in our meta-analysis. Our study demonstrated that the dexamethasone group was more effective than the placebo group in term of VAS score at 24 h(P meta-analysis demonstrated that dexamethasone decreased postoperative pain, the incidence of POVN, and total opioid consumption effectively which played a critical role in rapid recovery to TKA. However, we still need large sample size, high quality studies to explore the relationship between complications and dose response to give the final conclusion. Copyright © 2018. Published by Elsevier Ltd.

  18. Use of the Dexamethasone-Corticotrophin Releasing Hormone Test to Assess Hypothalamic-Pituitary-Adrenal Axis Function in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Eman A. Hasan

    2009-01-01

    Full Text Available Objectives. Hypothalamic-Pituitary-Adrenal axis function may be abnormal in rheumatoid arthritis (RA. A pilot study in 7 patients suggested impaired glucocorticoid feedback in some patients after the dexamethasone-corticotrophin releasing hormone (CRH test. This study aimed to investigate the dexamethasone-corticotrophin releasing factor test in a larger group of patients and relate the results to characteristics of the disease. Methods. Outpatients with active RA (≥3 swollen and tender joints and C-reactive protein > 10 mg/L took dexamethasone (1.5 mg at 23:00 hour in the evening. Next day, baseline saliva and plasma samples were collected, CRH was infused at 11:00 hour, and 4 serial blood and saliva samples were collected. Plasma samples were stored at −80∘C and a radioimmunoassay performed for saliva and plasma cortisol. Results. All 20 participants showed normal dexamethasone suppression and mounted no response to the CRH challenge. In samples with measurable cortisol, there was a strong correlation between saliva and plasma values (r = 0.876, n = 26, P<.01. Conclusion. No abnormalities were found in the Dexamethasone-CRH test in RA patients in contrast to a previous pilot study. Salivary cortisol measurement may offer an alternative noninvasive technique to plasma cortisol in RA patients in future studies.

  19. Magnetic hyaluronic acid nanospheres via aqueous Diels-Alder chemistry to deliver dexamethasone for adipose tissue engineering.

    Science.gov (United States)

    Jia, Yang; Fan, Ming; Chen, Huinan; Miao, Yuting; Xing, Lian; Jiang, Bohong; Cheng, Qifan; Liu, Dongwei; Bao, Weikang; Qian, Bin; Wang, Jionglu; Xing, Xiaodong; Tan, Huaping; Ling, Zhonghua; Chen, Yong

    2015-11-15

    Biopolymer-based nanospheres have great potential in the field of drug delivery and tissue regenerative medicine. In this work, we present a flexible way to conjugate a magnetic hyaluronic acid (HA) nanosphere system that are capable of vectoring delivery of adipogenic factor, e.g. dexamethasone, for adipose tissue engineering. Conjugation of nanospheres was established by aqueous Diels-Alder chemistry between furan and maleimide of HA derivatives. Simultaneously, a furan functionalized dexamethasone peptide, GQPGK, was synthesized and covalently immobilized into the nanospheres. The magnetic HA nanospheres were fabricated by encapsulating super-paramagnetic iron oxide nanoparticles, which exhibited quick magnetic sensitivity. The aqueous Diels-Alder chemistry made nanospheres high binding efficiency of dexamethasone, and the vectoring delivery of dexamethasone could be easily controlled by a external magnetic field. The potential application of the magnetic HA nanospheres on vectoring delivery of adipogenic factor was confirmed by co-culture of human adipose-derived stem cells (ASCs). In vitro cytotoxicity tests demonstrated that incorporation of dexamethasone into magnetic HA nanospheres showed high efficiency to promote ASCs viabilities, in particular under a magnetic field, which suggested a promising future for adipose regeneration applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels-Alder chemistry for adipose tissue engineering.

    Science.gov (United States)

    Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

    2015-11-01

    A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels-Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37°C were studied. The results demonstrated that the aqueous Diels-Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. Copyright © 2015. Published by Elsevier B.V.

  1. Modeling Induction Motor Imbalances

    DEFF Research Database (Denmark)

    Armah, Kabenla; Jouffroy, Jerome; Duggen, Lars

    2016-01-01

    This paper gives a study into the development of a generalized model for a three-phase induction motor that offers flexibility of simulating balanced and unbalanced parameter scenarios. By analyzing the interaction of forces within the motor, we achieve our main objective of deriving the system d...

  2. Reversal of dexamethasone induced insulin resistance in 3T3L1 adipocytes by 3β-taraxerol of Mangifera indica.

    Science.gov (United States)

    Sangeetha, K N; Shilpa, K; Jyothi Kumari, P; Lakshmi, B S

    2013-02-15

    The present study investigates the efficacy of Mangifera indica ethyl acetate extract (MIEE) and its bioactive compound, 3β-taraxerol in the reversal of dexamethasone (DEX) induced insulin resistance in 3T3L1 adipocytes. MIEE and 3β-taraxerol were evaluated for their ability to restore impaired glucose uptake and, expression of molecular markers in the insulin signaling pathway induced by DEX in 3T3L1 adipocytes using 2-deoxy-D-[1-(3)H] glucose uptake assay and ELISA. An insulin resistant model has been developed using a glucocorticoid, DEX on 3T3L1 adipocytes. Insulin resistant condition was observed at 24h of DEX induction wherein a maximum degree of resistance of about 50% was measured based on inhibition of glucose uptake, which was confirmed using cytotoxicity analysis. The developed model of insulin resistance was studied in comparison to positive control rosiglitazone. DEX induced inhibition of glucose uptake and the expression of insulin signaling markers GLUT4 and PI3K were found to be restored by 3β-taraxerol and MIEE, thus delineating its mechanism of action in the reversal of insulin resistance. 3β-Taraxerol effectively restored DEX induced desensitization via restoration of PI3K and GLUT4 expression. To conclude, since 3β-taraxerol exhibits significant effect in reversing insulin resistance it can be further investigated as an insulin resistance reversal agent. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. Combination therapy with carfilzomib, lenalidomide and dexamethasone (KRd) results in an unprecedented purity of the stem cell graft in newly diagnosed patients with myeloma.

    Science.gov (United States)

    Tageja, Nishant; Korde, Neha; Kazandjian, Dickran; Panch, Sandhya; Manasanch, Elisabet; Bhutani, Manisha; Kwok, Mary; Mailankody, Sham; Yuan, Constance; Stetler-Stevenson, Maryalice; Leitman, Susan F; Sportes, Claude; Landgren, Ola

    2018-05-04

    Still, many physicians give 4 cycles of combination therapy to multiple myeloma patients prior to collection of stem cells for autologous bone marrow transplant. This tradition originates from older doxorubicin-containing regiments which limited the number of cycles due to cumulative cardiotoxicity. Using older regiments, most patients had residual myeloma cells in their autologous stem-cell grafts during collection. Emerging data show that newly diagnosed multiple myeloma patients treated with modern carfilzomib/lenalidomide/dexamethasone (KRd) therapy, on average, take 6 cycles until reaching minimal residual disease (MRD) negativity. We assessed newly diagnosed patients treated with KRd focusing MRD status both in the individual patient's bone marrow, and the corresponding autologous hematopoietic progenitor cell grafts during collection. Per protocol, stem-cell collection was allowed after 4 to 8 cycles of KRd. We found similar stem-cell yield independent of the number of cycles of KRd. At stem-cell collection, 11/30 patients (36.6%) were MRD negative in their bone marrow; all 11 patients had MRD negative hematopoietic progenitor cell grafts. Furthermore, 18/19 patients who were MRD positive in their bone marrows also had MRD negative hematopoietic progenitor cell grafts. These observations support 6 cycles of KRd as an efficacious and safe induction strategy prior to stem-cell collection.

  4. High current induction linacs

    International Nuclear Information System (INIS)

    Barletta, W.; Faltens, A.; Henestroza, E.; Lee, E.

    1994-07-01

    Induction linacs are among the most powerful accelerators in existence. They have accelerated electron bunches of several kiloamperes, and are being investigated as drivers for heavy ion driven inertial confinement fusion (HIF), which requires peak beam currents of kiloamperes and average beam powers of some tens of megawatts. The requirement for waste transmutation with an 800 MeV proton or deuteron beam with an average current of 50 mA and an average power of 40 MW lies midway between the electron machines and the heavy ion machines in overall difficulty. Much of the technology and understanding of beam physics carries over from the previous machines to the new requirements. The induction linac allows use of a very large beam aperture, which may turn out to be crucial to reducing beam loss and machine activation from the beam halo. The major issues addressed here are transport of high intensity beams, availability of sources, efficiency of acceleration, and the state of the needed technology for the waste treatment application. Because of the transformer-like action of an induction core and the accompanying magnetizing current, induction linacs make the most economic sense and have the highest efficiencies with large beam currents. Based on present understanding of beam transport limits, induction core magnetizing current requirements, and pulse modulators, the efficiencies could be very high. The study of beam transport at high intensities has been the major activity of the HIF community. Beam transport and sources are limiting at low energies but are not significant constraints at the higher energies. As will be shown, the proton beams will be space-charge-dominated, for which the emittance has only a minor effect on the overall beam diameter but does determine the density falloff at the beam edge

  5. Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation

    Science.gov (United States)

    Robinson, Erik; Kaushal, Sunjay; Alaboson, Justice; Sharma, Sudhish; Belagodu, Amogh; Watkins, Claire; Walker, Brandon; Webster, Gregory; McCarthy, Patrick; Ho, Dean

    2016-02-01

    Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 +/- 0.42 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P atrial fibrillation was decreased in rabbits with PPX[AMIO, DEX] films compared to control (9.5 +/- 6.8 s vs. 187.6 +/- 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 +/- 1.2 s vs. 103.2 +/- 178 s, p = 0.004). DEX/AMIO-loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications.Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to

  6. A Randomized Cross‐over Study of High‐dose Metoclopramide plus Dexamethasone versus Granisetron plus Dexamethasone in Patients Receiving Chemotherapy with High‐dose Cisplatin

    Science.gov (United States)

    Eguchi, Kenji; Shinkai, Tetsu; Tamura, Tomohide; Ohe, Yuichiro; Nisio, Masato; Kunikane, Hiroshi; Arioka, Hitoshi; Karato, Atsuya; Nakashima, Hajime; Sasaki, Yasutsuna; Tajima, Kinuko; Tada, Noriko; Saijo, Nagahiro

    1994-01-01

    We carried out a randomized, single‐blind, cross‐over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high‐dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty‐four patients with primary or metastatic lung cancer, given single‐dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively (P=0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P= 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty‐four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed. PMID:7829401

  7. Comparison of the Effect of Ondansetrone - Dexamethasone, Dexamethasone – Metoclopeamide and Ondansetron - Normal Saline in Decreasing Post Operative Nausa and Vomitting (PONV after Middle Ear Surgery

    Directory of Open Access Journals (Sweden)

    Haddadi Soudabeh

    2009-09-01

    Full Text Available Background: The incidence of post-operative nausea and vomitting (PONV is increased after middle ear surgery and it may complicate and interact with reconstruction after surgery, so prevention and treatment of these complications are necessary.The aim of this study was to evaluate the efficacy of anti-emetic combinations in decreasing the PONV after middle ear surgery.Materials and methods: This double blind clinical trial was carried out during 2007-2008 on 111 patients of 15-45 years old with ASA I-II who were candidates for elective middle ear surgery under general anesthesia. The patients were divided into three groups. Patients in the ON group received Ondansetrone 0.1mg/kg + Nacl 0.9% 2cc, OD group received Ondansetrone 0.1mg/kg + Dexamethasone 0.15mg/kg and MD group received Dexamethasone 0.15mg/kg+ Metoclopramide 0.15mg/kg intravenously just before the end of surgery. The patients were evaluated for nausea, vomiting, need of anti-emetic drugs and drug dosage in recovery, 1-6, 6-12 and 12-24 hours after operation and then all data were statistically analyzed by SPSS software, Chi-square, ANOVA and t- Test. P<0.05 was significant.Results: There were no significant differences among three groups in age and sex. The incidence of PONV among 3 groups was not significantly different during 24 hours after operation. (P=0.271 but the incidence of PONV in the first six hours was different among 3 groups (P=0.007 (ON: 8.1%, OD: 0%, MD: 21.6%. Also Metoclopramide consumption was significant between three groups. Conclusion: This study showed that the need to anti-emetic drugs in first 6 hours was the least in OD group, but the difference in the incidence of PONV was not significant otherwise.

  8. Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma.

    Science.gov (United States)

    Gay, Francesca; Rajkumar, S Vincent; Coleman, Morton; Kumar, Shaji; Mark, Tomer; Dispenzieri, Angela; Pearse, Roger; Gertz, Morie A; Leonard, John; Lacy, Martha Q; Chen-Kiang, Selina; Roy, Vivek; Jayabalan, David S; Lust, John A; Witzig, Thomas E; Fonseca, Rafael; Kyle, Robert A; Greipp, Philip R; Stewart, A Keith; Niesvizky, Ruben

    2010-09-01

    The objective of this case-matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low-dose dexamethasone (BiRd) vs. lenalidomide/low-dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital-Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention-to-treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very-good-partial-response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time-to-progression (median 48.3 vs. 27.5 months, P = 0.071), and progression-free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3-year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3-4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case-matched analysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. © 2010 Wiley-Liss, Inc.

  9. Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: a randomized crossover phase II trial (KDOG 1002).

    Science.gov (United States)

    Ishido, Kenji; Higuchi, Katsuhiko; Azuma, Mizutomo; Sasaki, Tohru; Tanabe, Satoshi; Katada, Chikatoshi; Yano, Takafumi; Wada, Takuya; Koizumi, Wasaburo

    2016-10-01

    We conducted a randomized trial to compare the safety and effectiveness of aprepitant, granisetron, and dexamethasone (AGD) with those of palonosetron and dexamethasone (PD) in patients who received highly emetogenic chemotherapy (HEC). Patients with esophageal or gastric cancer who were scheduled to receive HEC including at least 60 mg/m of cisplatin as the first-line treatment were randomly assigned to receive AGD (oral aprepitant 125 mg on day 1 and 80 mg on days 2-3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone 6.6 mg on day 1 and oral dexamethasone 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous dexamethasone 13.2 mg on day 1 and oral dexamethasone 8 mg on days 2-3). The primary endpoint was a complete response during the overall study period (0-120 h after the start of chemotherapy) in the first cycle. Eighty-five patients were enrolled, and 84 were eligible. The complete response rate did not differ between the treatment groups, but the proportion of patients with no vomiting was significantly higher in the AGD group than in the PD group (81.4 vs. 58.5%; P=0.031). The results of a quality-of-life survey indicated that the proportion of patients with no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1 vs. 53.7%; P=0.020). The primary endpoint of complete response was not achieved, but AGD seems to be more effective than PD for the prevention of HEC-induced vomiting.

  10. Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial

    DEFF Research Database (Denmark)

    Rasmussen, M L; Dierking, G; Lech, K

    2008-01-01

    BACKGROUND: Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy. METHODS: One hundred...... and sixteen patients were randomly assigned to either group A (paracetamol+placebo x 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexamethasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg...... or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg x 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation...

  11. Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

    Science.gov (United States)

    Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

    2011-08-01

    To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  12. EFFECTS OF DEXAMETHASONE AND PHENIRAMINE MALEATE ON HEMODYNAMIC AND RESPIRATORY PARAMETERS AFTER CEMENTATION IN CEMENTED PARTIAL HIP PROSTHESIS.

    Science.gov (United States)

    Yektaş, Abdulkadir; Gümüş, Funda; Totoz, Tolga; Gül, Nurten; Erkalp, Kerem; Alagöl, Ayşin

    2015-02-01

    To prevent hemodynamic and respiratory changes that are likely to occur during cementation in partial hip prosthesis by prophylactic use of pheniramine maleate and dexamethasone. The study included 40 patients aged between 60 and 85 years with an American Society ofAnesthesiologists (ASA) grade of II-III who underwent partial hip prosthesis. Just after spinal anesthesia, 4 mL normal saline was pushed in patients in Group S, whereas 45.5 mg pheniramine maleate and 8 mg dexamethasone mixture was pushed intravenously in a total volume of 4 mL in patients in Group PD. Amounts of atropine and adrenaline administered after cementation were significantly higher in Group S than in Group PD (P pheniramine maleate and dexamethasone in partial hip prosthesis led to an increase in SpO2 value and a decrease in the utilization of adrenaline and atropine after cementation.

  13. Examination of dexamethasone sodium sulfate and hyperbaric oxygenation in experimentally produced cerebral edema. With special reference to their combination

    Energy Technology Data Exchange (ETDEWEB)

    Kanaya, H; Onodera, H; Watanabe, M; Kamata, K [Iwate Medical Coll., Morioka (Japan). School of Medicine

    1975-06-01

    Dexamethasone sodium sulfate and hyperbaric oxygenation were used for experimentally produced cerebral edema for the examination of the water content of the brain and cerebrovascular permeability using /sup 203/Hg as the tracer. Although dexamethasone starts lowering vascular permeability of the edematous brain at one hour after the intravenous injection, a lapse of 24 hours is required until the water content returns to normal. Although hyperbaric oxygenation dose not reduce cerebrovascular permeability, it brings back the water content of the brain to normal immediately after pressurization. Since the combination of dexamethasone and hyperbaric oxygenation maintains the water content of the brain almost normal throughout the entire process, it is ideal for the treatment of cerebral edema.

  14. Comparison of clinical effects of prilocaine, dexamethasone added to prilocaine and levobupivacaine on brachial plexus block

    International Nuclear Information System (INIS)

    Saritas, A.; Sabuncu, C.

    2014-01-01

    Objective: To determine whether the addition of 8mg dexamethasone to axillary brachial plexus block would prolong the duration of sensory and motor block in patients undergoing hand and forearm surgery. Methods: The prospective, randomised, double-blinded study was conducted at the Eskisehir Osmangazi University Medical School, Turkey, from October 2008 to December 2009. It comprised 45 American Society of Anaesthesiologists grade I and II patients under elective surgery of the hand and forearm. The patients were randomly divided into 3 groups: 5 mg/kg of 2% prilocaine was applied to Group 1; 5 mg/kg of 2% prilocaine +8mg of dexamethasone (2ml) was applied to Group 2; and 1.5 mg/kg 0.5% levobupivacaine was applied to Group 3. Sensory and motor block onset time as well as the duration of motor and sensory block of those were monitored and recorded. SPSS 15 was used for statistical analysis. Results: Of the 45 patients, 27 (60%) were men and 18 (40%) were women. There was no significant difference among the groups in terms of demographic data. Based on the duration of motor and sensory block, similar periods of time in Group 1 and Group 2 were noted, whereas this period was statistically different and significantly longer in Group 3 (p<0.001). There were no complications encountered. Conclusion: The addition of dexamethasone to prilocaine prolonged the duration of sensory and motor block. It could be used as an effective adjuvant agent. Levobupivacain could be a more appropriate local anaesthetic in post-operative analgesia and prolonged surgical procedures. (author)

  15. Development and Evaluation of a Novel Microemulsion of Dexamethasone and Tobramycin for Topical Ocular Administration.

    Science.gov (United States)

    Bachu, Rinda Devi; Stepanski, Marina; Alzhrani, Rami M; Jung, Rose; Boddu, Sai H S

    2018-05-01

    The purpose of this study was to develop and evaluate a novel dexamethasone- and tobramycin-loaded microemulsion for its potential for treating anterior segment eye infections. The microemulsion was evaluated for pH, particle size, zeta potential, light transmittance, morphology, and in vitro drug release. Sterility of the microemulsion was evaluated by direct as well as plate inoculation methods. Anti-inflammatory activity of dexamethasone, bactericidal activity of tobramycin, and cytotoxicity of the microemulsion were assessed and compared to that of the marketed eye drop suspension (Tobradex ® ). Histological evaluation was performed in bovine corneas to assess the safety of microemulsion in comparison to Tobradex suspension. In addition, the stability of the microemulsion was studied at 4°C, 25°C, and 40°C. The pH of the microemulsion was close to the pH of tear fluid. The microemulsion displayed an average globule size under 20 nm, with light transmittance around 95%-100%. The aseptically prepared microemulsion remained sterile for up to 14 days. The cytotoxicity of the microemulsion in bovine corneal endothelial cells was comparable to that of the Tobradex suspension. The anti-inflammatory activity of dexamethasone and the antibacterial activity of tobramycin from the microemulsion were significantly higher than those of the Tobradex suspension (P microemulsion was found to be stable at 4°C and 25°C for 3 months. In conclusion, the developed microemulsion could be explored as a suitable alternative to the marketed suspension for treating anterior segment eye infections.

  16. Extended low-dose dexamethasone suppression test for diagnosis of atypical Cushing's syndrome in dogs.

    Science.gov (United States)

    Fowler, K M; Frank, L A; Morandi, F; Whittemore, J C

    2017-07-01

    The purpose of this study was to evaluate extension of the low-dose dexamethasone suppression (LDDS) test from 8 h to 12 h to detect possible hypercortisolemia associated with atypical hyperadrenocorticism (AHAC). Twelve client-owned dogs were enrolled in the study: 6 healthy dogs (group 1) and 6 dogs with suspected AHAC (group 2). Baseline EDTA plasma samples were collected for endogenous ACTH determination using an immunoradiometric assay. Serum samples were collected before and at 4, 8, 10, and 12 h post-administration of 0.01 mg/kg dexamethasone IV for cortisol concentration determination via chemiluminescent assay. Mean endogenous ACTH concentration did not differ between groups (group 1: 22.4 pg/mL, group 2: 20.0 pg/mL; P > 0.2). Mean baseline cortisol concentration also did not differ significantly between groups (group 1: 3.03 μg/dL, group 2: 4.95 μg/dL; P > 0.2) nor was there any difference in mean cortisol concentration between the groups at any other time point (P > 0.2). The cortisol concentration from 1 dog in group 2 suppressed to 0.7 μg/dL at 8 h but increased to 1.5 μg/dL at 10 h and 3.7 μg/dL at 12 h post-dexamethasone. Based on results of this study, use of an extended LDDS test could not differentiate between healthy dogs and dogs with AHAC. Diagnosis of AHAC should continue to be based on prior established criteria until new testing has been identified. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Comparative evaluation of megadose methylprednisolone with dexamethasone for treatment of primary typical optic neuritis

    Directory of Open Access Journals (Sweden)

    Menon Vimala

    2007-01-01

    Full Text Available Aim: To compare the efficacy of intravenous methylprednisolone and intravenous dexamethasone on visual recovery and evaluate their side-effects for the treatment of optic neuritis. Materials and Methods: Prospective, randomized case-controlled study including 21 patients of acute optic neuritis presenting within eight days of onset and with visual acuity less then 20/60 in the affected eye who were randomly divided into two groups. Group I received intravenous dexamethasone 200 mg once daily for three days and Group II received intravenous methylprednisolone 250 mg/six-hourly for three days followed by oral prednisolone for 11 days. Parameters tested were pupillary reactions, visual acuity, fundus findings, color vision, contrast sensitivity, Goldmann visual fields and biochemical investigations for all patients at presentation and follow-up. Results: Both groups were age and sex-matched. LOGMAR visual acuity at presentation was 1.10 ± 0.52 in Group I and 1.52 ± 0.43 in Group II. On day 90 of steroid therapy, visual acuity improved to 0.28 ± 0.33 in Group I and 0.36 ± 0.41 in Group II ( P =0.59. At three months there was no statistically significant difference in the color vision, contrast sensitivity, stereoacuity, Goldman fields and the amplitude and latency of visually evoked response between the two groups. The concentration of vitamin C, glucose, sodium, potassium, urea and creatinine were within the reported normal limits. Conclusion: Intravenous dexamethasone is an effective treatment for optic neuritis. However, larger studies are required to establish it as a safe, inexpensive and effective modality for the treatment of optic neuritis.

  18. Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy

    Directory of Open Access Journals (Sweden)

    Timothy J. Pianta

    2017-03-01

    Full Text Available Background/Aims: Plasma cystatin C (pCysC may be superior to serum creatinine (sCr as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. Methods: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1, and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague–Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. Results: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16–34%], relative increases were ≥ 50% in 9 patients (35% for pCysC compared with 2 (8% for sCr (p = 0.04 and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC, but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. Conclusions: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.

  19. Does Growth Impairment Underlie the Adverse Effects of Dexamethasone on Development of Noradrenergic Systems?

    Science.gov (United States)

    Slotkin, Theodore A; Ko, Ashley; Seidler, Frederic J

    2018-06-20

    Glucocorticoids are given in preterm labor to prevent respiratory distress but these agents evoke neurobehavioral deficits in association with reduced brain region volumes. To determine whether the neurodevelopmental effects are distinct from growth impairment, we gave developing rats dexamethasone at doses below or within the therapeutic range (0.05, 0.2 or 0.8 mg/kg) at different stages: gestational days (GD) 17-19, postnatal days (PN) 1-3 or PN7-9. In adolescence and adulthood, we assessed the impact on noradrenergic systems in multiple brain regions, comparing the effects to those on somatic growth or on brain region growth. Somatic growth was reduced with exposure in all three stages, with greater sensitivity for the postnatal regimens; brain region growth was impaired to a lesser extent. Norepinephrine content and concentration were reduced depending on the treatment regimen, with a rank order of deficits of PN7-9 > PN1-3 > GD17-19. However, brain growth impairment did not parallel reduced norepinephrine content in magnitude, dose threshold, sex or regional selectivity, or temporal pattern, and even when corrected for reduced brain region weights (norepinephrine per g tissue), the dexamethasone-exposed animals showed subnormal values. Regression analysis showed that somatic growth impairment accounted for an insubstantial amount of the reduction in norepinephrine content, and brain growth impairment accounted for only 12%, whereas specific effects on norepinephrine accounted for most of the effect. The adverse effects of dexamethasone on noradrenergic system development are not simply related to impaired somatic or brain region growth, but rather include specific targeting of neurodifferentiation. Copyright © 2018. Published by Elsevier B.V.

  20. Revisiting the Dexamethasone Suppression Test in unipolar major depression: an exploratory study

    Directory of Open Access Journals (Sweden)

    Rihmer Zoltan

    2008-11-01

    Full Text Available Abstract Background Important methodological questions still exist concerning the Dexamethasone Suppression Test (DST, including the possibility of a better way of interpreting it. The aim of the present study was to explore the feasibility of an alternative way of interpreting DST results. Methods A total of 50 patients with major depression aged 41.0 ± 11.4 years old participated in the study. Past and present suicide attempts were recorded. Psychometric assessment included the Hamilton Depression Rating Scale (HDRS, the Hamilton Anxiety Scale (HAS, the Newcastle Depression Diagnostic Scale (NDDS, the Diagnostic Melancholia Scale (DMS and the General Assessment of Functioning (GAF scale. The 1 mg DST protocol was used. Analysis methods included the chi square test and analysis of covariance (ANCOVA with Fisher least significant difference (LSD as post hoc tests. Results In all, 34 patients (68% were suppressors, 16 (32% were non-suppressors and 14 patients had cortisol values above 5 μg/dl at baseline. Baseline cortisol level did not influence the classical DST interpretation. A total of 18 patients (36% showed an increase of their cortisol levels after dexamethasone administration and 32 patients (64% showed a decrease. Reducers had less melancholic features, similar levels of depression, better sleep and less suicidal thoughts in comparison to increasers. No relationship of DST to suicidality was found. Discussion The present study explored the pattern of cortisol response to dexamethasone suppression and suggested an alternative way of coding and interpreting the DST on the basis of whether the cortisol levels remain stable or increase vs decrease after the administration of cortisol. The results put forward a complex way of understanding the relationship of the DST results with clinical symptoms.

  1. Dexamethasone as Adjuvant to Bupivacaine Prolongs the Duration of Thermal Antinociception and Prevents Bupivacaine-Induced Rebound Hyperalgesia via Regional Mechanism in a Mouse Sciatic Nerve Block Model

    Science.gov (United States)

    An, Ke; Elkassabany, Nabil M.; Liu, Jiabin

    2015-01-01

    Background Dexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear. Methods A mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg). Results High-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone

  2. Inductive Communication System Design Summary

    Science.gov (United States)

    1978-09-01

    The report documents the experience obtained during the design and development of the Inductive Communications System used in the Morgantown People Mover. The Inductive Communications System is used to provide wayside-to-vehicle and vehicle-to-waysid...

  3. Repeat Intravitreal Dexamethasone Implant for Refractory Cystoid Macular Edema in Syphilitic Uveitis

    Directory of Open Access Journals (Sweden)

    Cassandra C. Lautredou

    2018-01-01

    Full Text Available Purpose. To report the successful utilization of adjunctive repeat intravitreal corticosteroid therapy for the treatment of cystoid macular edema in syphilis-related uveitis. Methods/Patients. An HIV-positive patient with treated ocular syphilis who developed refractory cystoid macular edema (CME was treated with repeat intravitreal corticosteroid therapy including dexamethasone intravitreal implants. Results. Treatment led to the resolution of CME and improvement in visual acuity. Conclusions. Intravitreal corticosteroid therapy may be a viable adjunctive treatment for refractory CME in patients with treated syphilitic uveitis. Corticosteroid-induced exacerbation of infection is unlikely in patients with an adequate serologic treatment response.

  4. Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo.

    Science.gov (United States)

    Akhter, S R; Ikezaki, H; Gao, X P; Rubinstein, I

    1999-05-01

    The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (FITC-dextran; mol mass, 70 kDa) from the in situ hamster cheek pouch (P grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.

  5. Dexamethasone-responsive hypertension in young women with suppressed renin and aldosterone

    International Nuclear Information System (INIS)

    Hoefnagels, W.H.L.; Hofman, J.A.; Smals, A.G.H.; Drayer, J.I.M.; Kloppenborg, P.W.C.; Benraad, T.J.

    1978-01-01

    Pronounced hypoaldosteronism was found in three young women with hypertension and symptoms of mineralocorticoid overproduction - i.e., hyporeninaemia, hypokalaemia, and a fall in blood-pressure after diuretic therapy. Plasma 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone concentrations were normal. Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion. The data suggest that hypertension in these patients is maintained by overproduction of an unknown adrenocorticotropin-dependent mineralocortocoid. (author)

  6. Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Dexamethasone Sodium Phosphate.

    Science.gov (United States)

    Wu, George; Yeung, Stanley; Chen, Frank

    2017-01-01

    Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone combination therapy is the standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein, we describe the physical and chemical stability of an injectable emulsion of the Neurokinin-1 receptor antagonist rolapitant 185 mg in 92.5 mL (free base, 166.5 mg in 92.5 mL) admixed with either 2.5 mL of dexamethasone sodium phosphate (10 mg) or 5 mL of dexamethasone sodium phosphate (20 mg). Admixtures were prepared and stored in two types of container closures (glass and Crystal Zenith plastic bottles) and four types of intravenous administration tubing sets (or intravenous tubing sets). The assessment of the physical and chemical stability was conducted on admixtures packaged in bottled samples stored at room temperature (20°C to 25°C under fluorescent light) and evaluated at 0, 1, and 6 hours. For admixtures in intravenous tubing sets, the assessment of physicochemical stability was performed after 0 and 7 hours of storage at 20°C to 25°C, and then after 20 hours (total 27 hours) under refrigeration (2°C to 8°C) and protected from light. Physical stability was assessed by visually examining the bottle contents under normal room light and measuring turbidity and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations through high-performance liquid chromatographic analysis. Results showed that all samples were physically compatible throughout the duration of the study. The admixtures stayed within narrow and acceptable ranges in pH, turbidity, and particulate matter. Admixtures of rolapitant and dexamethasone were chemically stable when stored in glass and Crystal Zenith bottles for at least 6 hours at room temperature, as well as in the four selected intravenous tubing sets for 7 hours at 20°C to 25°C and then for 20 (total 27 hours) hours at 2°C to 8°C. No loss of potency

  7. Simultaneous Determination of Ciprofloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Eye Drops by HPLC

    OpenAIRE

    Katakam, Prakash; Sireesha, Karanam R.

    2012-01-01

    A liquid chromatographic method was developed and validated for the simultaneous determination of ciprofloxacin hydrochloride and dexamethasone sodium phosphate in bulk and pharmaceutical formulations. Optimum separation was achieved in less than 5 min using a C18 column (250 mmx4.6 mm i.d, 5μ particle size) by isocratic elution. The mobile phase consisting of a mixture of mixed phosphate buffer (pH 4) and acetonitrile (65:35, v/v) was used. Column effluents were monitored at 254 nm at a flow...

  8. In Vivo Imaging of Microglia Turnover in the Mouse Retina After Ionizing Radiation and Dexamethasone Treatment

    DEFF Research Database (Denmark)

    Alt, C.; Runnels, J. M.; Mortensen, L. J.

    2014-01-01

    irradiation with a confocal scanning laser ophthalmoscope that we custom-built specifically for multicolor imaging of the murine retina. RESULTS. Ionizing radiation resulted in loss of 75% of the resident retinal microglia population after 70 days. Recruitment of BMDCs was delayed with respect...... dexamethasone preserves resident microglia and minimizes recruitment of BMDCs after ionizing radiation exposure and BMT.......PURPOSE. Gamma irradiation and bone marrow transplantation (BMT) are established clinical procedures for the treatment of hematologic malignancies. The radiation targets cells in the bone marrow, but injury to other tissues, including the central nervous system (CNS), have been reported. Here, we...

  9. Aqueous Humor Penetration and Biological Activity of Moxifloxacin 0.5% Ophthalmic Solution Alone or with Dexamethasone 0.1.

    Science.gov (United States)

    Gomes, Rachel L R; Viana, Rodrigo Galvão; Melo, Luiz Alberto S; Cruz, Alessandro Carvalho; Suenaga, Eunice Mayumi; Kenyon, Kenneth R; Campos, Mauro

    2017-03-01

    To compare aqueous humor concentrations of topically applied moxifloxacin 0.5% ophthalmic solution alone or in combination with dexamethasone 0.1% and to correlate these concentrations with the minimum inhibitory concentrations (MICs) for common endophthalmitis-causing organisms. Sixty-eight patients undergoing routine phacoemulsification with intraocular lens implantation received either moxifloxacin 0.5% alone or moxifloxacin 0.5% combined with dexamethasone. For both groups, 1 drop of the test solution was instilled 4 times daily 1 day preoperatively and 1 drop 1 h preoperatively. An aqueous humor sample obtained immediately before paracentesis was submitted to high-performance liquid chromatography-tandem mass spectrometry to determine the moxifloxacin concentration. The mean concentrations of moxifloxacin were 986.6 ng/mL in the moxifloxacin with dexamethasone group and 741.3 ng/mL in the moxifloxacin group (P = 0.13). Moxifloxacin concentrations of all samples exceeded the MICs for Staphylococcus epidermidis, S. aureus, and Streptococcus pneumoniae. All samples in the moxifloxacin with dexamethasone group and 94% in the moxifloxacin group achieved the MIC for Enterococcus species. For quinolone-resistant S. aureus, the MIC was achieved in 29% in the moxifloxacin with dexamethasone group and 9% in the moxifloxacin group (P = 0.06). Aqueous humor moxifloxacin concentrations were higher when topically administrated in combination with dexamethasone compared to the moxifloxacin alone. However, this difference was not statistically significant. Nevertheless, the MICs of the most common pathogens associated with endophthalmitis were exceeded in both study groups.

  10. Dexamethasone treatment induces susceptibility of outbred Webster mice to experimental infection with Besnoitia darlingi isolated from opossums (Didelphis virginiana).

    Science.gov (United States)

    Elsheikha, Hany M; Rosenthal, Benjamin M; Mansfield, Linda S

    2005-04-01

    The Sarcocystidae comprise a diverse, monophyletic apicomplexan parasite family, most of whose members form intracellular cysts in their intermediate hosts. The extent of pathology associated with such cyst formation can range widely. We currently lack experimental animal models for many of these infections. Here we explored dexamethasone treatment as a means to render outbred mice susceptible to Besnoitia darlingi infection and demonstrated that this approach allows viable parasites to be subsequently isolated from these mice and maintained in tissue culture. Besnoitia bradyzoites recovered from crushed cysts derived from naturally infected opossums (Didelphis virginiana) replicated and reproduced the development of besnoitiosis in mice treated with dexamethasone (0.5 mg/ml drinking water) daily for 12 days post infection (DPI). Isolates recovered from the peritoneal exudates of these mice were viable and were maintained in long-term tissue cultures. In contrast, control mice given saline without dexamethasone and challenged with similar bradyzoites remained clinically normal for up to 70 DPI. An additional group of mice challenged with the same inoculum of bradyzoites and given dexamethasone at the same concentration and treated with sulfadiazine (1 mg/ml drinking water) daily for 12 DPI also remained normal for up to 70 DPI. Severe disease developed more rapidly in dexamethasone-treated mice inoculated with culture-derived B. darlingi tachyzoites than in those inoculated with cyst-derived bradyzoites. B. darlingi tachyzoite-infected, untreated control mice developed signs of illness at 18 DPI. In contrast, mice treated with sulfadiazine showed no clinical signs up to 50 DPI. Although dexamethasone treatment was required to establish B. darlingi infection in outbred mice inoculated with opossum-derived B. darlingi bradyzoites, no such treatment was required for mice inoculated with culture-derived B. darlingi tachyzoites. Finally, sulfadiazine was highly

  11. Pre- and postoperative dexamethasone does not reduce bleaching-induced tooth sensitivity: A randomized, triple-masked clinical trial.

    Science.gov (United States)

    Rezende, Márcia; Bonafé, Elize; Vochikovski, Laína; Farago, Paulo Vitor; Loguercio, Alessandro Dourado; Reis, Alessandra; Kossatz, Stella

    2016-01-01

    Tooth sensitivity (TS) is the most common side effect of dental bleaching therapies. Dexamethasone has been used with tooth bleaching to reduce TS. The efficacy of dexamethasone for this purpose has not been well studied. The authors conducted a triple-masked, randomized, clinical trial with a parallel design involving 63 healthy participants who received either a placebo or dexamethasone. The placebo or dexamethasone (8 milligrams) was administered 1 hour before the in-office bleaching (35% hydrogen peroxide) and extra doses of 4 mg were administered every 6 hours for a total of 48 hours. TS was recorded on 2 scales: visual analog scale (0-10) and numeric rating scale (0-4) in different periods. The color evaluations were performed before and 1 month after dental bleaching with visual shade guides VITA Classical (VITA Zahnfabrik) and VITA Bleachedguide 3D-MASTER (VITA Zahnfabrik), and for a shade guide evaluation, the authors used a digital spectrophotometer, VITA Easyshade (VITA Zahnfabrik). The absolute risk of TS was evaluated by a Fisher exact test. Data of TS intensity using the NRS scale for the 2 groups were compared with Mann-Whitney and Friedman tests, whereas data from the visual analog scale were evaluated by 2-way repeated measures analysis of variance. The color changes between groups were compared using a t test (α = .05). In both groups, the authors detected a high risk of TS, which was approximately 90%. No significant difference was observed in terms of TS intensity. A whitening of approximately 3 shade guide units of the VITA Classical was detected in both groups, which were statistically similar. The use of dexamethasone before bleaching did not reduce the risk and intensity of bleaching-induced TS. The use of the steroidal anti-inflammatory agent dexamethasone was not capable of preventing TS arising from in-office dental bleaching. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

  12. Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study.

    Science.gov (United States)

    Michopoulos, Vasiliki; Norrholm, Seth D; Stevens, Jennifer S; Glover, Ebony M; Rothbaum, Barbara O; Gillespie, Charles F; Schwartz, Ann C; Ressler, Kerry J; Jovanovic, Tanja

    2017-09-01

    Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all pextinction blocks during both conditions (p's≤0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (pextinction and discrimination in individuals with PTSD. Copyright © 2017 Elsevier Ltd. All rights

  13. Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing's syndrome in obese patients.

    Science.gov (United States)

    Sahin, Mustafa; Kebapcilar, Levent; Taslipinar, Abdullah; Azal, Omer; Ozgurtas, Taner; Corakci, Ahmet; Akgul, Emin Ozgur; Taslipinar, Mine Yavuz; Yazici, Mahmut; Kutlu, Mustafa

    2009-01-01

    Obesity is currently a major public health problem and one of the potential underlying causes of obesity in a minority of patients is Cushing's syndrome (CS). Traditionally, the gold standard screening test for CS is 1 mg dexamethasone overnight suppression test. However, it is known that obese subjects have high false positive results with this test. We have therefore compared the 1 mg and 2 mg overnight dexamethasone suppression tests in obese subjects. Patients whose serum cortisol after ODST was >50 nM underwent and a low-dose dexamethasone suppression test (LDDST); 24-hour urine cortisol was collected for basal urinary free cortisol (UFC). For positive results after overnight 1-mg dexamethasone suppression test we also performed the overnight 2-mg dexamethasone suppression test. We prospectively evaluated 100 patients (22 men and 78 women, ranging in age from 17 to 73 years with a body mass index (BMI) >30 kg/m2 who had been referred to our hospital-affiliated endocrine clinic because of simple obesity. Suppression of serum cortisol to suppression. Thyroid function tests, lipid profiles, homocysteine, antithyroglobulin, anti-thyroid peroxidase antibody levels, vitamin B12, folate levels, insulin resistance [by homeostasis model assessment (HOMA)] and 1.0 mg postdexamethasone (postdex) suppression cortisol levels were measured. We found an 8% false-positive rate in 1 mg overnight test and 2% in 2 mg overnight test (p=0.001). There was no correlation between the cortisol levels after ODST and other parameters. Our results indicate that the 2 mg overnight dexamethasone suppression test (ODST) is more convenient and accurate than 1-mg ODST as a screening test for excluding CS in subjects with simple obesity.

  14. Pharmaceutical induction of ApoE secretion by multipotent mesenchymal stromal cells (MSCs

    Directory of Open Access Journals (Sweden)

    Whitney Mandolin J

    2008-09-01

    Full Text Available Abstract Background Apolipoprotein E (ApoE is a molecular scavenger in the blood and brain. Aberrant function of the molecule causes formation of protein and lipid deposits or "plaques" that characterize Alzheimer's disease (AD and atherosclerosis. There are three human isoforms of ApoE designated ε2, ε3, and ε4. Each isoform differentially affects the structure and function of the protein and thus the development of disease. Homozygosity for ApoE ε4 is associated with atherosclerosis and Alzheimer's disease whereas ApoE ε2 and ε3 tend to be protective. Furthermore, the ε2 form may cause forms of hyperlipoproteinemia. Therefore, introduction of ApoE ε3 may be beneficial to patients that are susceptible to or suffering from these diseases. Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs are adult progenitor cells found in numerous tissues. They are easily expanded in culture and engraft into host tissues when administered appropriately. Furthermore, MSCs are immunosuppressive and have been reported to engraft as allogeneic transplants. In our previous study, mouse MSCs (mMSCs were implanted into the brains of ApoE null mice, resulting in production of small amounts of ApoE in the brain and attenuation of cognitive deficits. Therefore human MSCs (hMSCs are a promising vector for the administration of ApoE ε3 in humans. Results Unlike mMSCs, hMSCs were found not to express ApoE in culture; therefore a molecular screen was performed for compounds that induce expression. PPARγ agonists, neural stem cell conditioned medium, osteo-inductive media, dexamethasone, and adipo-inductive media (AIM were tested. Of the conditions tested, only AIM or dexamethasone induced sustained secretion of ApoE in MSCs and the duration of secretion was only limited by the length of time MSCs could be sustained in culture. Upon withdrawal of the inductive stimuli, the ApoE secretion persisted for a further 14 days. Conclusion The data

  15. Induction technology optimization code

    International Nuclear Information System (INIS)

    Caporaso, G.J.; Brooks, A.L.; Kirbie, H.C.

    1992-01-01

    A code has been developed to evaluate relative costs of induction accelerator driver systems for relativistic klystrons. The code incorporates beam generation, transport and pulsed power system constraints to provide an integrated design tool. The code generates an injector/accelerator combination which satisfies the top level requirements and all system constraints once a small number of design choices have been specified (rise time of the injector voltage and aspect ratio of the ferrite induction cores, for example). The code calculates dimensions of accelerator mechanical assemblies and values of all electrical components. Cost factors for machined parts, raw materials and components are applied to yield a total system cost. These costs are then plotted as a function of the two design choices to enable selection of an optimum design based on various criteria. (Author) 11 refs., 3 figs

  16. Glass manufacturing through induction

    International Nuclear Information System (INIS)

    Boen, R.; Paya, B.; Roscini, M.; Fautrelle, Y.; Tuaz, F.; Delage, D.

    1991-01-01

    Oxides and glasses are electrical and thermal insulators, but show the characteristic of being weakly conductors of electricity when they are melt. It is then possible to heat them through HF induction. This interesting property allows the development of a melting process in cold crucible induction furnace. The process is being studied and developed by a consortium made up of CFEI, CEA Marcoule, ELECTRICITE DE FRANCE and MADYLAM laboratory. The studies include 2 parts: a) One experimental part to develop the technology and research for satisfying configurations, through a small size platform (10 to 30 kg/h). The long run continuous pouring melting tests made on different kinds of glass allow to go-on with industrial range units. b) One theoretical part to understand the magneto-thermo-hydraulic phenomenon hardly in relation with the heavy dependence of the physical characteristics (electrical and heat conductivities, viscosity) according to temperature. 6 refs., 4 figs [fr

  17. Inductive energy storage commutator

    International Nuclear Information System (INIS)

    Gavrilov, I.M.

    1987-01-01

    An inductive energy storage commutator is described. The value of commutated current is up to 800 A, the voltage amplitude in the load is up to 50 kV, the working frequency is equal to 1-50 Hz, the commutated power is up to 40 MW. The commutating device comprises of the first stage commutator having two in-series connected modules of the BTSV - 800/235 high-voltage thyristor unit, the second stage commutator containing three GMI-43A parallel connected powerful pulsed triodes, a commutating capacitor, an induction coil, two supplementary high-voltage thyristor keys (20 in-series connected thyristors T2-300 (13 class)), load, control pulse shapers, thyristor keys, power supply

  18. Pulse induction heating

    Energy Technology Data Exchange (ETDEWEB)

    Vasiliev, A S; Kachanov, B Y; Kogan, B V

    1993-12-31

    Induction heating and three types of pulse processes were studied. It was found that in pulse processes the frequency and pulse duration of heat treatments do not remain constant. High frequency pulse heat treatments can be used on sprayed coatings; such treatments will result in stronger surfaces with no cracks. For induction hardening, the rate of specific power was 1 to 1.5 kW/sq.cm, for forging it was 0.2 to 0.3 kW/sq.cm and for melting it was 0.05 to 0.1 kW/sq.cm. The application of pulse heating will result in higher rates of specific power.

  19. Inductive Reasoning: A Training Approach

    Science.gov (United States)

    Klauer, Karl Josef; Phye, Gary D.

    2008-01-01

    Researchers have examined inductive reasoning to identify different cognitive processes when participants deal with inductive problems. This article presents a prescriptive theory of inductive reasoning that identifies cognitive processing using a procedural strategy for making comparisons. It is hypothesized that training in the use of the…

  20. Effect of dexamethasone on skeletal muscle Na+,K+ pump subunit specific expression and K+ homeostasis during exercise in humans

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Ovesen, Jakob; Thomassen, Martin

    2008-01-01

    The effect of dexamethasone on Na(+),K(+) pump subunit expression and muscle exchange of K(+) during exercise in humans was investigated. Nine healthy male subjects completed a randomized double blind placebo controlled protocol, with ingestion of dexamethasone (Dex: 2 x 2 mg per day) or placebo...... (Pla) for 5 days. Na(+),K(+) pump catalytic alpha1 and alpha2 subunit expression was approximately 17% higher (P ...). The results indicate that an increased Na(+),K(+) pump expression per se is of importance for thigh K(+) reuptake at the onset of low and moderate intensity exercise, but less important during high intensity exercise....

  1. Antenatal Dexamethasone Exposure in Preterm Infants Is Associated with Allergic Diseases and the Mental Development Index in Children

    Directory of Open Access Journals (Sweden)

    Wan-Ning Tseng

    2016-12-01

    Full Text Available Background: Antenatal steroid administration may benefit fetal lung maturity in preterm infants. Although some studies have shown that this treatment may increase asthma in childhood, the correlation between antenatal dexamethasone exposure and allergic diseases remains unclear. The purpose of this study is to investigate the association between antenatal dexamethasone and T cell expression in childhood allergic diseases. Methods: We recruited a cohort of preterm infants born at Kaohsiung Chang Gung Memorial Hospital between 2007 and 2010 with a gestational age of less than 35 weeks and body weight at birth of less than 1500 g. The status of antenatal exposure to steroids and allergic diseases were surveyed using a modified ISAAC questionnaire for subjects aged 2–5 years old. We analyzed Th1/Th2/Th17 expression of mRNA, cytokines (using the Magpix® my-system, and mental development index (MDI. Results: Among the 40 patients that were followed, the data showed that the antenatal dexamethasone exposure group (N = 24 had a significantly higher incidence of allergic diseases (75.0% vs. 18.8%, p < 0.0001 when compared to the non-dexamethasone exposure group (N = 16, especially with regard to asthma (41.7% vs. 0.0%, p = 0.003 and allergic rhinitis (58.3% vs. 18.8%, p = 0.013, but not atopic dermatitis. No statistical difference was observed in the mRNA expression levels of total white blood cell count between the dexamethasone exposure and non-exposure groups (p > 0.05. However, the asthma group had higher IL-5 levels (p = 0.009, and the MDI was shown to be significantly higher in the dexamethasone exposure group (90.38 ± 3.31 vs. 79.94 ± 3.58, p = 0.043 while no significant difference was found between the PDI of the two groups. Conclusions: Exposure to antenatal dexamethasone in preterm infants will increase their susceptibility to allergic diseases, particularly asthma and allergic rhinitis. Preterm infants’ exposure to antenatal

  2. Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma

    Directory of Open Access Journals (Sweden)

    Diane TW Chang

    2009-05-01

    Full Text Available Diane TW Chang, Michael C Herceg, Richard A Bilonick, Larissa Camejo, Joel S Schuman, Robert J NoeckerDepartment of Ophthalmology, University of Pittsburgh Medical Center, Eye Center, Pittsburgh, PA, USAPurpose: To evaluate whether dexamethasone injected intracamerally at the conclusion of surgery can safely and effectively reduce postoperative inflammation and improve surgical outcomes in eyes with and without glaucoma.Methods: Retrospective chart review of 176 consecutive eyes from 146 patients receiving uncomplicated phacoemulsification (PE (n = 118 total, 82 with glaucoma, glaucoma drainage device (GDD (n = 35, combined PE/GDD (n = 11 and combined PE/endoscopic cyclophotocoagulation (n = 12. Ninety-one eyes from 76 patients were injected with 0.4 mg dexamethasone intracamerally at the conclusion of surgery. All eyes received standard postoperative prednisolone and ketorolac eyedrops. Outcomes were measured for four to eight weeks by subjective complaints, visual acuity (VA, slit-lamp biomicroscopy, intraocular pressure (IOP and postoperative complications.Results: Dexamethasone significantly reduced the odds of having an increased anterior chamber (AC cell score after PE (p = 0.0013. Mean AC cell score ± SD in nonglaucomatous eyes was 1.3 ± 0.8 in control and 0.8 ± 0.7 with dexamethasone; scores in glaucomatous eyes were 1.3 ± 0.7 in control and 0.9 ± 0.8 with dexamethasone. Treated nonglaucomatous eyes had significantly fewer subjective complaints after PE (22.2% vs 64.7% in control; p = 0.0083. Dexamethasone had no significant effects on VA, corneal changes, IOP one day and one month after surgery, or long-term complications.Conclusions: Intracameral dexamethasone given at the end of cataract surgery significantly reduces postoperative AC cells in eyes with and without glaucoma, and improves subjective reports of recovery in nonglaucomatous eyes. There were no statistically significant risks of IOP elevation or other complications in

  3. A Retrospective Study Evaluating the Effect of Low Doses of Perineural Dexamethasone on Ropivacaine Brachial Plexus Peripheral Nerve Block Analgesic Duration.

    Science.gov (United States)

    Schnepper, Gregory D; Kightlinger, Benjamin I; Jiang, Yunyun; Wolf, Bethany J; Bolin, Eric D; Wilson, Sylvia H

    2017-09-23

    Examination of the effectiveness of perineural dexamethasone administered in very low and low doses on ropivacaine brachial plexus block duration. Retrospective evaluation of brachial plexus block duration in a large cohort of patients receiving peripheral nerve blocks with and without perineural dexamethasone in a prospectively collected quality assurance database. A single academic medical center. A total of 1,942 brachial plexus blocks placed over a 16-month period were reviewed. Demographics, nerve block location, and perineural dexamethasone utilization and dose were examined in relation to block duration. Perineural dexamethasone was examined as none (0 mg), very low dose (2 mg or less), and low dose (greater than 2 mg to 4 mg). Continuous catheter techniques, local anesthetics other than ropivacaine, and block locations with fewer than 15 subjects were excluded. Associations between block duration and predictors of interest were examined using multivariable regression models. A subgroup analysis of the impact of receiving dexamethasone on block duration within each block type was also conducted using a univariate linear regression approach. A total of 1,027 subjects were evaluated. More than 90% of brachial plexus blocks contained perineural dexamethasone (≤4 mg), with a median dose of 2 mg. Increased block duration was associated with receiving any dose of perineural dexamethasone (P block duration did not differ with very low- or low-dose perineural dexamethasone after controlling for other factors (P = 0.420). Perineural dexamethasone prolonged block duration compared with ropivacaine alone; however, duration was not greater with low-dose compared with very low-dose perineural dexamethasone. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  4. Lexicographic Path Induction

    DEFF Research Database (Denmark)

    Schürmann, Carsten; Sarnat, Jeffrey

    2009-01-01

    Programming languages theory is full of problems that reduce to proving the consistency of a logic, such as the normalization of typed lambda-calculi, the decidability of equality in type theory, equivalence testing of traces in security, etc. Although the principle of transfinite induction......, and weak normalization for Gödel’s T follows indirectly; both have been formalized in a prototypical extension of Twelf....

  5. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960's to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore's Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail

  6. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1997-01-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at Lawrence Livermore National Laboratory (LLNL) from the early 1960s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400-ns pulses. The Advanced Test Accelerator (ATA) built at Livermore close-quote s Site 300 produced 10,000-Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and Lawrence Berkeley National Laboratory (LBNL). This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high-current, short-pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail. copyright 1997 American Institute of Physics

  7. Stability-indicating liquid Chromatographic assaymethod for Opthalmic solutions containing combination of Dexamethasone and Chloramphenicol

    International Nuclear Information System (INIS)

    Rao, R.M.; Al-Ashban, R.M.; Shah, A.H.

    2004-01-01

    A selective high-performance chromatographic procedure for the stability monitoring of ophthalmic solutions containing a combination of dexamethasone and chloramphenicolis demonstrated. The separation of the active components and the degradation product of chloramphenicol (1-amino-1-(4-nitrophenyl)-propane-1, 3diol) was achieved on a u-Bondapack C-18 column ( 5 um, 300 mm x 3.9 mm) maintained at ambient temperature (15-20C) by utilizing a mobile phase consisting acidified water (5% actified water with glacial acetic acid ) : acetonitrile : triethyl amine 700 : 300 : 2and pH was adjusted to 5.0 by using 10 M Na OH. The flow rate was 1.5 ml min-1; and elutes were followed with UV-detection at 254 nm. Complete resolution of dexamethasone, chloramphenicol and its hydrolytic product could be attained. The sensitivity, accuracy and specificity were tested. The method was successfully applied in post-marketing stability of the commercial batches of ophthalmic solutions. (author)

  8. Dexamethasone, all trans retinoic acid and interferon alpha 2a in patients with refractory multiple myeloma.

    Science.gov (United States)

    Avilés, A; Rosas, A; Huerta-Guzmán, J; Talavera, A; Cleto, S

    1999-02-01

    Few effective regimen are available for patients with refractory multiple myeloma (RMM). Generally, responses are scarce and disease free survival is very short. We developed a new therapeutic option in these patients using dexamethasone (40 mg/m2, i.v., daily, days 1 to 4), all-trans retinoic acid (45 mg/m2, po, daily, days 5 to 14) and interferon alpha 2a (9.0 MU, daily, subcutaneously, days 5 to 14). The treatment was administered every 21 days for 6 cycles. In a pilot study, 12 patients, heavily treated with chemotherapy and radiotherapy and in some cases with interferon, were allocated to receive the afore mentioned treatment. Response was observed in 10 patients (83%). With a median follow-up of 36.1 months (range 27 to 41), seven patients remain alive and disease-free without any treatment. Two patients were failures and have died due to tumor progression. Toxicity was mild and all patients received treatment according to the planned doses of drugs. The use of biological modifiers in combination with dexamethasone offer a safe and effective therapeutic option in patients with refractory multiple myeloma. More studies are warranted to define the role of this type of treatment.

  9. Additive manufacturing of scaffolds with dexamethasone controlled release for enhanced bone regeneration.

    Science.gov (United States)

    Costa, Pedro F; Puga, Ana M; Díaz-Gomez, Luis; Concheiro, Angel; Busch, Dirk H; Alvarez-Lorenzo, Carmen

    2015-12-30

    The adoption of additive manufacturing in tissue engineering and regenerative medicine (TERM) strategies greatly relies on the development of novel 3D printable materials with advanced properties. In this work we have developed a material for bone TERM applications with tunable bioerosion rate and dexamethasone release profile which can be further employed in fused deposition modelling (the most common and accessible 3D printing technology in the market). The developed material consisted of a blend of poly-ϵ-caprolactone (PCL) and poloxamine (Tetronic®) and was processed into a ready-to-use filament form by means of a simplified melt-based methodology, therefore eliminating the utilization of solvents. 3D scaffolds composed of various blend formulations were additively manufactured and analyzed revealing blend ratio-specific degradation rates and dexamethasone release profiles. Furthermore, in vitro culture studies revealed a similar blend ratio-specific trend concerning the osteoinductive activity of the fabricated scaffolds when these were seeded and cultured with human mesenchymal stem cells. The developed material enables to specifically address different regenerative requirements found in various tissue defects. The versatility of such strategy is further increased by the ability of additive manufacturing to accurately fabricate implants matching any given defect geometry. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Differentiation of malignant and degenerative bone lesions using dexamethasone interventional 3- and 24-hour bone scintigraphy

    International Nuclear Information System (INIS)

    Bhatnagar, A.; Mondal, A.; Kashyap, R.; Sharma, R.K.; Sharma, R.; Chakravarty, S.K.; Bihari, V.; Sawroop, K.; Chopra, M.K.; Soni, N.L.

    1994-01-01

    Seventy-seven adult patients with suspected skeletal metastases were divided into two groups. In group A (n=30), following intravenous administration of 20 mCi (740 MBq) of technetium-99m methylene diphosphonate ( 99m Tc-MDP), 3- and 24-h scintigraphy of bone lesions was performed. The 24/3 h lesion to bone background radiouptake ratio (RUR) was calculated for each lesion. In group B (n=47), the same procedure was followed with dexamethasone intervention (10 mg in 24 h) following the 3-h acquisition. In group A, after determination of the critical point, malignant and degenerative bone lesions could be separated with a sensitivity, specificity and accuracy of 0.76, 0.72 and 0.73, respectively. The mean RUR of the malignant lesions was 1.20± 0.23, and that of the benign lesions, 0.95± 0.15. In group B cases, significantly increased sensitivity, specificity and accuracy of 0.87, 0.94 and 0.92, respectively, were found (P<0.001). The mean RUR of the malignant lesions was 1.48± 0.34, and that of degenerative lesions, 0.88± 0.19. Dexamethasone interventional bone scintigraphy seems to be a new cost-effective method for differentiating malignant from degenerative bone lesions using the RUR. (orig.)

  11. Structured Self-Rated Response to Iontophoresis with Verapamil and Dexamethasone in Peyronie’s Disease

    Directory of Open Access Journals (Sweden)

    Abas Kokab

    2014-01-01

    Full Text Available Introduction. New therapies evolve for the treatment of Peyronie's disease (PD including the application of dexamethasone and verapamil using Electro Motive Drug Administration (EMDA. Patients and Methods. Patients with PD were routinely offered Potaba, Vitamin E, tamoxifen or colchicine for 6 to 18 months and for those with no improvement, 18 applications of dexamethasone and verapamil using EMDA occurred over a 6 week period. All 30 patients receiving EMDA therapy completed a questionnaire before and after treatment. The data was collected from December 2004 to November 2009 and analysed to evaluate the effectiveness of the treatment. Results. Median age of patients was 59 (range 39–71. Curvature was the most common presenting complaint (73.3% followed by pain (23.3%, erectile dysfunction (13.3%, and lump (13.3%. 24/30 (80% reported an improvement in symptoms after EMDA. 16 of the responders (66.7% had a stable plaque for at least 6 months. The patients who complained of shortening of the penis (P=0.003 or lowered sexual desire (P=0.024 expressed subsequently significant response to treatment. There was statistically significant (P=0.019 improvement of penile deviation reported by responding men. Conclusion. A significant proportion of patients who received EMDA reported decreased curvature following iontophoresis. No serious adverse reactions developed.

  12. Acute Changes in Mentation in a Patient with Hepatic Cirrhosis Treated with High Doses of Dexamethasone.

    Science.gov (United States)

    Dabul, Luis; Droney, Andrew; Oms, Juan; Sanchez-Gonzalez, Marcos A

    2017-09-10

    Despite the anti-inflammatory benefits of steroids in the management of multiple medical conditions, they are associated with undesired metabolic and psychiatric side effects. We present a case of a 57-year-old Hispanic man with hepatic cirrhosis due to hepatitis C and no past medical history of psychiatric illnesses who became delirious after treatment with high doses of intravenous Dexamethasone. The patient presented to Larkin Community Hospital, USA with complaints of lower back pain requiring treatment with steroids for severe lumbar central canal stenosis. After three days of treatment, the patient became disoriented to time and place, grossly psychotic with auditory hallucinations and disorganized behavior, manic, aggressive, combative, restless, hard to redirect, and unable to follow commands. He met the criteria for a diagnosis of substance-induced psychotic disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM) V. Furthermore, the patient had worsening hepatic profile, a high ammonia level of 125 umol/L, and clinical findings consistent with West Haven classification grade 2 encephalopathy. Head computed tomography (CT) scan was normal. He was treated with discontinuation of steroids, lactulose, and Haloperidol returning to baseline mental status after 48 hours. The patient's hospitalization was complicated with a prolonged hospital stay after lumbar surgery. This case illustrates that treatment with high doses of Dexamethasone in a patient with hepatic cirrhosis can cause acute changes in mental status by (i) inducing delirium, and (ii) precipitating hepatic encephalopathy.

  13. Anterior migration of dexamethasone implant in a pseudophakic patient with intact posterior capsule

    Directory of Open Access Journals (Sweden)

    Nilufer Kocak

    2014-01-01

    Full Text Available Intravitreal application of Ozurdex ® (Allergan, Inc., Irvine, CA, USA which is a biodegradable, sustained-release dexamethasone implant has been reported to be effective in the treatment of macular edema. Migration of such implant into the anterior chamber has been recently described in cases without perfect zonular or the posterior capsular integrity. Herein, we report the first case with anterior migration of Ozurdex ® implant that mislocated just behind the intraocular lens (IOL in an intact capsular bag. It is thought that such implant migrated anteriorly towards into the posterior chamber through weak zonules as the present case had a medical history of uneventful phacoemulsification surgery with the implantation of posterior chamber IOL. However, the migrated implant was well tolerated since there was no sign of the corneal complication, rise in intraocular pressure, and anterior chamber reaction. Close follow-up was scheduled to find out any signs of anterior segment pathology. Meanwhile dexamethasone implant completely degraded at the 4 th month of postoperative follow-up.

  14. Effect of Dexamethasone and Pheniramine Maleate in Patients Undergoing Elective Laparoscopic Cholecystectomy.

    Science.gov (United States)

    Shrestha, B B; Karmacharya, M; Gharti, B B; Timilsina, B; Ghimire, P

    2014-01-01

    Laparoscopic cholecystectomy (LC) is elective surgical procedure for uncomplicated gallstone disease and gallbladder polyp. The objective of this study was to assess the efficacy of Dexamethasone and Pheniramine hydrogen maleate on reducing stress response and pain after surgery in patients undergoing laparoscopic cholecystectomy. After obtaining approval from the institutional ethics committee and written informed consent, 120 patients undergoing elective laparoscopic cholecystectomy were enrolled in the study from Sep 2103 to Aug 2014 at Department of Surgery, Manipal College of Medical Sciences, Pokhara, Nepal. Patients were randomized to receive either 8mg/2ml of Dexamethasone + 45.5/2ml Pheniramine hydrogen maleate (treatment group, n= 60) or 5 ml of normal saline (control group, n=60) 90 minutes before skin incision. There was a reduction of total bilirubin, C-reactive protein (CRP) value and Visual Analogue Score (VAS) in treatment group as compared to control group (p Pheniramine hydrogen maleate prior to surgical skin incision helps to reduce both postoperative pain and acute physiological stress.

  15. Inductive reasoning 2.0.

    Science.gov (United States)

    Hayes, Brett K; Heit, Evan

    2018-05-01

    Inductive reasoning entails using existing knowledge to make predictions about novel cases. The first part of this review summarizes key inductive phenomena and critically evaluates theories of induction. We highlight recent theoretical advances, with a special emphasis on the structured statistical approach, the importance of sampling assumptions in Bayesian models, and connectionist modeling. A number of new research directions in this field are identified including comparisons of inductive and deductive reasoning, the identification of common core processes in induction and memory tasks and induction involving category uncertainty. The implications of induction research for areas as diverse as complex decision-making and fear generalization are discussed. This article is categorized under: Psychology > Reasoning and Decision Making Psychology > Learning. © 2017 Wiley Periodicals, Inc.

  16. A taxonomy of inductive problems.

    Science.gov (United States)

    Kemp, Charles; Jern, Alan

    2014-02-01

    Inductive inferences about objects, features, categories, and relations have been studied for many years, but there are few attempts to chart the range of inductive problems that humans are able to solve. We present a taxonomy of inductive problems that helps to clarify the relationships between familiar inductive problems such as generalization, categorization, and identification, and that introduces new inductive problems for psychological investigation. Our taxonomy is founded on the idea that semantic knowledge is organized into systems of objects, features, categories, and relations, and we attempt to characterize all of the inductive problems that can arise when these systems are partially observed. Recent studies have begun to address some of the new problems in our taxonomy, and future work should aim to develop unified theories of inductive reasoning that explain how people solve all of the problems in the taxonomy.

  17. Haloperidol plus dexamethasone versus dexamethasone alone to prevent postoperative nausea and vomiting in patients undergoing ambulatory surgery: a randomized, controlled and double-blind study

    Directory of Open Access Journals (Sweden)

    Nelson Javier González

    2008-02-01

    Full Text Available

    BACKGROUND AND GOAL OF THE STUDY: haloperidol is an effective antiemetic drug. We sought to determine whether haloperidol and dexamethasone prophylaxis schemes decrease the incidence of postoperative nausea and vomiting (PONV in patients undergoing ambulatory surgery.

    MATERIALS AND METHODS: we enrolled 160 non-smoking females who received a standardized anesthesia technique including 8 mg of dexamethasone at the beginning of surgery. They were then randomized to receive either 1.5 mg of haloperidol (DH group or placebo (DP group 30 minutes before the end of surgery. The incidence of PONV was assessed by a blinded investigator at 30 minutes and at 2, 6 and 24 hours in the postoperative period. Analgesic requirements, ocular opening time and sedation were also assessed. The quantitative variables of normal distribution were evaluated with the t-student test and the ones with abnormal distribution, with the U-Mann Whitney test. Qualitative variables were evaluated with the Fisher test.

    RESULTS AND DISCUSSION: both groups were homogeneous in demographic characteristics (30.1 vs. 29.5 years, 55.9 vs. 56 kg and history of PONV in 21.5% vs. 21.2% in DH group vs. DP group, respectively. At 6 hours postoperatively we found no difference in the incidence of nausea (22.5% vs. 27.5%; RR: 0.81, CI 95%: 0.56 -1

  18. Linear induction motor

    International Nuclear Information System (INIS)

    Barkman, W.E.; Adams, W.Q.; Berrier, B.R.

    1978-01-01

    A linear induction motor has been operated on a test bed with a feedback pulse resolution of 5 nm (0.2 μin). Slewing tests with this slide drive have shown positioning errors less than or equal to 33 nm (1.3 μin) at feedrates between 0 and 25.4 mm/min (0-1 ipm). A 0.86-m (34-in)-stroke linear motor is being investigated, using the SPACO machine as a test bed. Initial results were encouraging, and work is continuing to optimize the servosystem compensation

  19. Dexamethasone-(C21-phosphoramide-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549

    Directory of Open Access Journals (Sweden)

    Coyne CP

    2016-08-01

    Full Text Available Cody P Coyne,1 Lakshmi Narayanan2 1Department of Basic Sciences, 2Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA Purpose: Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma, autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively “target” delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. Materials and methods: The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549 known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. Results: The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin

  20. Antibody induction versus corticosteroid induction for liver transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Wettergren, André; Wilson, Colin H

    2014-01-01

    BACKGROUND: Liver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell specific antibody induction compared with corticosteroid induction of immunosuppression after liver transplantation....... OBJECTIVES: To assess the benefits and harms of T-cell specific antibody induction versus corticosteroid induction for prevention of acute rejection in liver transplant recipients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register...... to identify additional trials. SELECTION CRITERIA: We included all randomised clinical trials assessing immunosuppression with T-cell specific antibody induction versus corticosteroid induction in liver transplant recipients. Our inclusion criteria stated that participants within each included trial should...

  1. Multimodal analgesia with gabapentin, ketamine and dexamethasone in combination with paracetamol and ketorolac after hip arthroplasty: a preliminary study

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Mathiesen, Ole; Dierking, Gerd

    2010-01-01

    It has been hypothesized that combinations of analgesics with different mechanisms of action may reduce or even prevent postoperative pain. We, therefore, investigated the analgesic effect of gabapentin, dexamethasone and low-dose ketamine in combination with paracetamol and ketorolac as compared...

  2. Effects of awakening and the use of topical dexamethasone and levofloxacin on the cytokine levels in tears following corneal transplantation.

    Science.gov (United States)

    Fodor, Mariann; Petrovski, Goran; Pásztor, Dorottya; Gogolák, Péter; Rajnavölgyi, Éva; Berta, András

    2014-01-01

    To study the short-term effect of eye opening and use of topical dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in human tears. Prospective experimental design was used for tear collection from eyes of 10 healthy controls and 20 patients four days after penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or levofloxacin. The concentrations of different cytokines were measured by cytometric bead array. At eye opening, IL-6 levels were higher in the PKP group as compared to the controls. Thirty minutes later, the released levels of IL-10, IL-13, IL-17, IFNγ, and CCL5 increased in controls, while CXCL8 decreased in both control and PKP groups. The release of the cytokines remained stable after 30 mins except for IFNγ, which showed a decrease in the controls following levofloxacin instillation. No short-term effects of the topically used dexamethasone and levofloxacin could be detected on the cytokine levels in controls and after PKP. Evidence of changes in the levels and time course of tear cytokines after awakening or eye opening could be established and the short-term confounding effects of dexamethasone and levofloxacin on the levels of released cytokines in human tears could be excluded.

  3. Switching to Aflibercept in Diabetic Macular Edema Not Responding to Ranibizumab and/or Intravitreal Dexamethasone Implant

    Directory of Open Access Journals (Sweden)

    Antoine Herbaut

    2017-01-01

    Full Text Available Purpose. To assess short-term functional and anatomical outcomes of refractory diabetic macular edema (DME following a switch from ranibizumab or dexamethasone to aflibercept. Methods. We included retrospectively eyes with persistent DME after at least 3 ranibizumab and/or one dexamethasone implant intravitreal injections (IVI. The primary endpoint was the mean change in visual acuity (VA at month 6 (M6 after switching. Results. Twenty-five eyes were included. Before switching to aflibercept, 23 eyes received a median of 9.5 ranibizumab, and among them, 6 eyes received one dexamethasone implant after ranibizumab and 2 eyes received only one dexamethasone implant. Baseline VA, before any IVI, was 52.9 ± 16.5 letters, and preswitch VA was 57.1 ± 19.6 letters. The mean VA gain was +8 letters (p=0.01 between preswitch and M6. The mean central retinal thickness was 470.8 ± 129.9 μm before the switch and 303.3 ± 59.1 μm at M6 (p=0.001. Conclusion. Switching to aflibercept in refractory DME results in significant functional and anatomical improvement. The study was approved by the France Macula Federation ethical committee (FMF 2017-138.

  4. Creation of lung-targeted dexamethasone immunoliposome and its therapeutic effect on bleomycin-induced lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Xue-Yuan Chen

    Full Text Available OBJECTIVE: Acute lung injury (ALI, is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM-loaded immunoliposome (NLP functionalized with pulmonary surfactant protein A (SP-A antibody (SPA-DXM-NLP in an animal model. METHODS: DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. RESULTS: The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. CONCLUSIONS: The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice.

  5. Effect of venous dexamethasone, oral caffeine and acetaminophen on relative frequency and intensity of postdural puncture headache after spinal anesthesia.

    Science.gov (United States)

    Masoudifar, Mehrdad; Aghadavoudi, Omid; Adib, Sajjad

    2016-01-01

    Postdural puncture headache (PDPH) is a relatively common complication after regional anesthesia, especially in younger people, bothersome to patients and needs prophylaxis to prevent this complication. This study was conducted aiming to determine the preventive effect of dexamethasone plus caffeine and acetaminophen on relative frequency and intensity of PDPH after spinal anesthesia. In a clinical trial study, 90 candidates for the lower extremities orthopedic elective operation were divided into two groups of 45 individuals each. Intervention group received the compound of 500 mg acetaminophen +65 mg oral caffeine +8 mg venous dexamethasone an hour before spinal blocking, and the control group received placebo tablets + a dexamethasone equivalent volume of venous normal saline. The level of postoperative headache at the time of entrance to recovery and discharge, 6, 12, 24, 48, and 72 h postoperatively were measured based on Visual Analog Scale criterion in the two groups and then compared with each other. During the study, 24 patients in the control group and 17 patients in the intervention group were afflicted with headache; however, with no significant difference (P = 0.14). Total frequency of headache incidence was 35 times in the control group and 27 times in the intervention group (P = 0.32). Though the taking of acetaminophen + caffeine + dexamethasone is associated with a decrease in headache intensity and duration and decrease in PDPH incidence, compared with placebo, however, no essentially and statistically significant effect was produced.

  6. Permissive effect of dexamethasone on the increase of proenkephalin mRNA induced by depolarization of chromaffin cells

    International Nuclear Information System (INIS)

    Naranjo, J.R.; Mocchetti, I.; Schwartz, J.P.; Costa, E.

    1986-01-01

    In cultured bovine chromaffin cells, changes in the dynamic state of enkephalin stores elicited experimentally were studied by measuring cellular proenkephalin mRNA, as well as enkephalin precursors and authentic enkephalin content of cells and culture media. In parallel, tyrosine hydroxylase mRNA and catecholamine cell content were also determined. Low concentrations (0.5-100 pM) of dexamethasone increased the cell contents of proenkephalin mRNA and enkephalin-containing peptides. High concentrations of the hormone(1 μM) were required to increase the cell contents of tyrosine hydroxylase mRNA and catecholamines. Depolarization of the cells with 10 μM veratridine resulted in a depletion of enkephalin and catecholamine stores after 24 hr. The enkephalin, but not the catecholamine, content was restored by 48 hr. An increase in proenkephalin mRNA content might account for the recovery; this increase was curtailed by tetrodotoxin and enhanced by 10 pM dexamethasone. Tyrosine hydroxylase mRNA content was not significantly modified by depolarization, even in the presence of 1 μM dexamethasone. Aldosterone, progesterone, testosterone, or estradiol (1 μM) failed to change proenkephalin mRNA. Hence, dexamethasone appears to exert a specific permissive action on the stimulation of the proenkephalin gene elicited by depolarization. Though the catecholamines and enkephalins are localized in the same chromaffin granules and are coreleased by depolarization, the genes coding for the processes that are rate limiting in the production of these neuromodulators can be differentially regulated

  7. Multimodal analgesia with gabapentin, ketamine and dexamethasone in combination with paracetamol and ketorolac after hip arthroplasty: a preliminary study

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Mathiesen, Ole; Dierking, Gerd

    2010-01-01

    It has been hypothesized that combinations of analgesics with different mechanisms of action may reduce or even prevent postoperative pain. We, therefore, investigated the analgesic effect of gabapentin, dexamethasone and low-dose ketamine in combination with paracetamol and ketorolac as compared...... with paracetamol and ketorolac alone after hip arthroplasty....

  8. Short-term effects of intravitreal dexamethasone implant (OZURDEX® on choroidal thickness in patients with naive branch retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Hasan Basri Arifoglu

    Full Text Available ABSTRACT Purpose: The objective of this study was to evaluate subfoveal choroidal thickness (SFCT using enhanced depth imaging optical coherence tomography (EDI-OCT in patients with naïve branch retinal vein occlusion (BRVO before and after intravitreal dexamethasone implant (Ozurdex® injection. Methods: Thirty-nine patients with unilateral BRVO and 35 healthy subjects were included in this prospective study. Choroidal thickness was evaluated by EDI-OCT at baseline and 1 month after dexamethasone implant. Results: The mean SFCT measured in 39 patients with BRVO was 299.41 ± 55.86 µm, significantly greater than that in contralateral eyes (283.76 ± 57.44 µm; p=0.009 and control eyes (276.14 ± 39.06 µm; p=0.044. The mean SFCT after the treatment was 279.64 ± 50.96 µm, significantly thinner than that before intravitreal dexamethasone therapy (p=0.004. Conclusions: SFCT in treatment-naive BRVO eyes was significantly greater than that in contralateral eyes and healthy eyes and decreased significantly after intravitreal dexamethasone implantation.

  9. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

    Science.gov (United States)

    Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

    2015-06-01

    Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

  10. Effect of Dexamethasone on Characteristics of Supraclavicular Nerve Block with Bupivacaine and Ropivacaine: A Prospective, Double-blind, Randomized Control Trial.

    Science.gov (United States)

    Bindal, Deeksha; Narang, Neeraj; Mahindra, Rekha; Gupta, Himanshu; Kubre, Jyotsna; Saxena, Anudeep

    2018-01-01

    Dexamethasone as an adjuvant to bupivacaine and ropivacaine for supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade. However, comparison of effect of dexamethasone (8 mg) when added to these two local anesthetics has not been well studied. This study was conducted to compare analgesic efficacy of dexamethasone as adjuvant to bupivacaine and ropivacaine in SCBP block. Nerve stimulator-guided SCBP block was given to 120 patients, randomly assigned to one of four groups: ( n = 30 in each group) Group B, BD, R, and RD received 30 ml (0.5%) bupivacaine + 2 ml saline, 30 ml (0.5%) bupivacaine + dexamethasone 8 mg, 30 ml (0.5%) ropivacaine + 2 ml saline, and 30 ml (0.5%) ropivacaine + dexamethasone 8 mg, respectively. Time for request of the first rescue analgesic, 24-h analgesic consumption, and different block characteristics were assessed. Student's t -test, Chi-square test, ANOVA were used for statistical analysis. Dexamethasone significantly prolonged time for request of the first rescue analgesic of both ropivacaine (1211.83 ± 32.86 vs. 283.17 ± 7.71 min){ p R, RD block. The addition of dexamethasone to bupivacaine and ropivacaine in SCBP block prolonged time for first rescue analgesia and reduced the requirement of rescue analgesics with faster onset and prolonged duration of sensory and motor block, with the effect being stronger with ropivacaine.

  11. A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial

    Directory of Open Access Journals (Sweden)

    Yoshida Y

    2015-11-01

    Full Text Available Yoichiro Yoshida,1 Keiji Hirata,2 Hiroshi Matsuoka,3 Shigeyoshi Iwamoto,4 Masahito Kotaka,5 Hideto Fujita,6 Naoya Aisu,1 Seiichiro Hoshino,1 Takeo Kosaka,6 Kotaro Maeda,3 Fumiaki Kiyomi,7 Yuichi Yamashita1 1Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan; 2Department of Surgery, Fukuoka Sanno Hospital, Fukuoka, Japan; 3Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan; 4Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan; 5Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan; 6Department of Surgical Oncology, Kanazawa Medical University, Uchinada, Japan; 7Academia, Industry and Government Collaborative Research Institute of Translational Medicine for Life Innovation, Fukuoka University, Fukuoka, Japan Background: Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%–20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions.Patients and methods: The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of

  12. Prophylactic Use of Oral Acetaminophen or IV Dexamethasone and Combination of them on Prevention Emergence Agitation in Pediatric after Adenotonsillectomy

    Directory of Open Access Journals (Sweden)

    Parvin Sajedi

    2014-01-01

    Full Text Available Background: The present study was aimed to evaluate the efficacy of acetaminophen plus dexamethasone on post-operative emergence agitation in pediatric adenotonsillectomy. Methods: A total of 128 patients were randomized and assigned among four groups as: Intravenous (IV dexamethasone, oral acetaminophen, IV dexamethasone plus oral acetaminophen, placebo. Group 1 received 0.2 mg/kg dexamethasone plus 0.25 mg/kg strawberry syrup 2 h before surgery. Group 2 received 20 mg/kg oral acetaminophen (0.25 ml/kg with 0.05 ml/kg IV normal saline. Group 3 received 20 mg/kg acetaminophen and 0.2 mg/kg dexamethasone intravenously. Group 4 received 0.25 ml/kg strawberry syrup and 0.05 ml/kg normal saline. Agitation was measured according to Richmond agitation sedation score in the post anesthetic care unit (PACU after admission, 10, 20 and 30 min after extubation. Pain score was measured with FACE scale. Nurse satisfaction was measured with verbal analog scale. If agitation scale was 3 ≥ or pain scale was 4 ≥ meperidine was prescribed. If symptoms did not control wit in 15 min midazolam was prescribed. Patients were discharged from PACU according Modified Alderet Score. Data were analyzed with ANOVA, Chi-square, and Kruskal-Wallis among four groups. P < 0.05 was considered statistically significant. Results: A total of 140 patients were recruited in the study, which 12 of them were excluded. Thus, 128 patients were randomized and assigned among four groups. The four treatment groups were generally matched at baseline data. Median of pain score in 0, 10, 20 and 30 min after extubation were different between each study group with the control group (<0.001, 0.003 respectively. Also median of agitation score in 0, 10, 20 and 30 min after extubation were different between each study group with the control group (<0.001. Incidence of pain and incidence of agitation after extubation were not statistically identical among groups (P < 0.001 and P = 0

  13. Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

    Science.gov (United States)

    Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

    2017-01-01

    Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

  14. β–Hydroxy β–Methylbutyrate Improves Dexamethasone-Induced Muscle Atrophy by Modulating the Muscle Degradation Pathway in SD Rat

    Science.gov (United States)

    Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Park, Chan Hum; Yoon, Changshin; Kim, Nam Deuk; Kim, Mi Kyung; Chung, Hae Young

    2014-01-01

    Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β–hydroxy β–methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy. PMID:25032690

  15. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1–2.4)). Furthermore, among INF-α treated patients, gene–gene interaction studies on IL1B C-3737T and NFКB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  16. Pulsed inductive HF laser

    Energy Technology Data Exchange (ETDEWEB)

    Razhev, A M; Kargapol' tsev, E S [Institute of Laser Physics, Siberian Branch, Russian Academy of Sciences, Novosibirsk (Russian Federation); Churkin, D S; Demchuk, S V [Novosibirsk State University, Novosibirsk (Russian Federation)

    2016-03-31

    We report the results of experimentally investigated dependences of temporal, spectral and spatial characteristics of an inductive HF-laser generation on the pump conditions. Gas mixtures H{sub 2} – F{sub 2}(NF{sub 3} or SF6{sub 6}) and He(Ne) – H{sub 2} – F{sub 2}(NF{sub 3} or SF{sub 6}) were used as active media. The FWHM pulse duration reached 0.42 μs. This value corresponded to a pulsed power of 45 kW. For the first time, the emission spectrum of an inductive HF laser was investigated, which consisted of seven groups of bands with centres around the wavelengths of 2732, 2736, 2739, 2835, 2837, 2893 and 2913 nm. The cross section profile of the laser beam was a ring with a diameter of about 20 mm and width of about 5 mm. Parameters of laser operation in the repetitively pulsed regime were sufficiently stable. The amplitude instability of light pulses was no greater than 5% – 6%. (lasers)

  17. Regulation of ATM induction

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.M.; Kearsley, J.H.; Lee, C.S.; Sarris, M.; De Murrell, D.

    2000-01-01

    Full text: ATM, the tumour suppressor protein mutated in ataxia-telangiectasia, is of pivotal importance in controlling the cells primary response to ionising radiation (IR) induced DNA damage. Mutations in ATM which reduce the level of the ATM protein and/or compromise ATM functions are known to give rise to radiosensitivity and defective cell cycle checkpoint control. In response to DNA damage ATM kinase is rapidly activated and initiates downstream signalling to cell cycle control molecules including p53. To investigate additional mechanisms of ATM control we have employed ATM antisense expression in cultured cells, western analyses and immunohistochemistry in situ. We report that ATM can be up-regulated up to 10-fold following exposure to low levels of ionising radiation. ATM radiation-induction was radiation dose dependent while the rapidity of the response indicates a post translational pathway. The concurrent time frames for the radiation-induction of ATM levels and the activation of ATM kinase activity appear to be complimentary in boosting ATM's protective response to IR induced DNA damage, especially in ATM 'low expressing' systems. We also provide the first report of ATM misregulation in 2 cancer patients, indicating that ATM is not only radio-protective but has possible implications in cancer, particularly breast cancer. These results have particular importance in defining the regulation of the ATM protein as an: adaptive radio-response; radio-prognostic market in tumours and normal tissue, and breast cancer marker

  18. Selective induction of cyclin B protein abrogates the G2 delay after irradiation

    International Nuclear Information System (INIS)

    Kao, G.; Muschel, R.J.; Maity, A.; Kunig, A.; McKenna, W.G.

    1996-01-01

    Purpose/Objective: Irradiation of tumor cells commonly results in G2 delay, which has been postulated to allow DNA repair and cell survival. The G2 delay after irradiation is also often marked in some cell lines by delayed expression of cyclin B protein, suggesting a role for cyclin B regulation. Investigations of these hypotheses however has been hampered by the inability to selectively perturb the G2 delay in a physiologic manner. Materials and Methods: We have devised a system, with which we are able to selectively induce cyclin B protein expression in vivo at specific points in the cell cycle, by transfecting Hela cells with an expression vector under control of a dexamethasone-inducible promoter. Experiments were subsequently performed by synchronizing, releasing, irradiating, inducing, and harvesting these cells through the cell cycle. Results: Irradiation with 5 Gy led to a pronounced G2 delay, reflected by markedly slowed progression into mitosis, concomitant with reduced expression of cyclin B protein. Induction of cyclin B after radiation in these cells abrogated the G2 delay by approximately doubling the rate at which the cells re-enter mitosis. Treatment of irradiated untransfected control cells with dexamethasone, in which cyclin B is not induced, led to minimal changes. Studies of effects of cyclin B induction on cyclin B localization (using immunofluorescence), cdc2 phosphorylation and activation will also be presented. Conclusion: This system should allow further investigations into fundamental mechanisms of cell cycle regulation after irradiation and DNA damage. This also provides direct evidence for the first time that cyclin B protein regulation may play a role in the G2 delay following irradiation in Hela cells, perhaps complementing phosphorylation events

  19. Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.

    Science.gov (United States)

    Richardson, Paul G; Bensinger, William I; Huff, Carol Ann; Costello, Caitlin L; Lendvai, Nikoletta; Berdeja, Jesus G; Anderson, Larry D; Siegel, David S; Lebovic, Daniel; Jagannath, Sundar; Laubach, Jacob P; Stockerl-Goldstein, Keith E; Kwei, Long; Clow, Fong; Elias, Laurence; Salman, Zeena; Graef, Thorsten; Bilotti, Elizabeth; Vij, Ravi

    2018-03-01

    Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0-14·7). Progression-free survival was 4·6 months (range, 0·4-17·3). Grade 3-4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3-4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  20. Dexamethasone attenuates VEGF expression and inflammation but not barrier dysfunction in a murine model of ventilator-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Maria A Hegeman

    Full Text Available BACKGROUND: Ventilator-induced lung injury (VILI is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar-capillary barrier dysfunction in an established murine model of VILI. METHODS: Healthy male C57Bl/6 mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with an inspiratory pressure of 10 cmH2O ("lower" tidal volumes of ∼7.5 ml/kg; LVT or 18 cmH2O ("higher" tidal volumes of ∼15 ml/kg; HVT. Dexamethasone was intravenously administered at the initiation of HVT-ventilation. Non-ventilated mice served as controls. Study endpoints included VEGF and inflammatory mediator expression in lung tissue, neutrophil and protein levels in bronchoalveolar lavage fluid, PaO2 to FiO2 ratios and lung wet to dry ratios. RESULTS: Particularly HVT-ventilation led to alveolar-capillary barrier dysfunction as reflected by reduced PaO2 to FiO2 ratios, elevated alveolar protein levels and increased lung wet to dry ratios. Moreover, VILI was associated with enhanced VEGF production, inflammatory mediator expression and neutrophil infiltration. Dexamethasone treatment inhibited VEGF and pro-inflammatory response in lungs of HVT-ventilated mice, without improving alveolar-capillary permeability, gas exchange and pulmonary edema formation. CONCLUSIONS: Dexamethasone treatment completely abolishes ventilator-induced VEGF expression and inflammation. However, dexamethasone does not protect against alveolar-capillary barrier dysfunction in an established murine model of VILI.

  1. Grain dust induces IL-8 production from bronchial epithelial cells: the effect of dexamethasone on IL-8 production.

    Science.gov (United States)

    Park, H S; Suh, J H; Kim, H Y; Kwon, O J; Choi, D C

    1999-04-01

    Recent publications have suggested an active participation of neutrophils to induce bronchoconstriction after inhalation of grain dust (GD). To further understand the role of neutrophils in the pathogenesis of GD-induced asthma, this investigation was designed to determine whether human bronchial epithelial cells could produce IL-8 production and to observe the effect of dexamethasone on IL-8 production. We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four concentrations (1 to 200 microg/mL) of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant, which was derived from the culture of PBMC from a GD-induced asthmatic subject under the exposure to 10 microg/mL of GD, and compared with those cultured without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. To evaluate the effect of dexamethasone on IL-8 production, four concentrations (5 to 5000 ng/mL) of dexamethasone were pre-incubated for 24 hours and the same experiments were repeated. There was significant production of IL-8 from bronchial epithelial cells with additions of GD in a dose-dependent manner (P < .05), which was significantly augmented with additions of PBMC supernatant (P < .05) at each concentration. Compared with the untreated sample, pretreatment of dexamethasone could induced a remarkable inhibitions (15% to 55%) of IL-8 production from bronchial epithelial cells in a dose-dependent manner. These results suggest that IL-8 production from bronchial epithelial cells may contribute to neutrophil recruitment occurring in GD-induced airway inflammation. The downregulation of IL-8 production by dexamethasone from bronchial epithelial cells may contribute to the efficacy of this compound in

  2. Effect of adding dexamethasone to bupivacaine on transversus abdominis plane block for abdominal hysterectomy: A prospective randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Amany S Ammar

    2012-01-01

    Full Text Available Purpose: Different adjuvants have been used to improve the quality and increase the duration of local anesthetics during various nerve block techniques. The current study was aimed to evaluate the effect of adding dexamethasone to bupivacaine on the quality and duration of transversus abdominis plane (TAP block. Methods: Sixty adult patients undergoing elective open abdominal hysterectomy were randomly allocated to receive TAP block using 20 mL of bupivacaine hydrochloride 0.25% + 2 mL saline 0.9% (control group, n=30 or 20 mL of bupivacaine hydrochloride 0.25% + 2 mL dexamethasone "8 mg" (dexamethasone group, n=30. The primary outcome was postoperative pain, as evaluated by visual analog scale (VAS for pain scoring at 1, 2, 4, 12, 24 and 48 h postoperatively, whereas the secondary outcomes were time to first analgesia (TFA, morphine consumption and the occurrence of nausea, vomiting or somnolence. Results: The pain VAS score was significantly lower at the postoperative 2 h (4.9 vs. 28.1, P=0.01, 4 h (12.2 vs. 31.1, P=0.01 and 12 h (15.7 vs. 25.4, P=0.02. Furthermore, TFA was significantly longer in the dexamethasone group (459.8 vs. 325.4 min, P=0.002, with lesser morphine requirements in the postoperative 48 h (4.9 vs. 21.2 mg, P=0.003 and lower incidence of nausea and vomiting (6 vs. 14, P=0.03. No complications attributed to the block were recorded. Conclusion: Addition of dexamethasone to bupivacaine in TAP block prolonged the duration of the block and decreased the incidence of nausea and vomiting.

  3. Effects of trophic exposure to diclofenac and dexamethasone on hematological parameters and immune response in freshwater fish.

    Science.gov (United States)

    Ribas, João Luiz Coelho; Zampronio, Aleksander R; Silva de Assis, Helena C

    2016-04-01

    The aim of the present study was to evaluate the effects of diclofenac and dexamethasone on hematological parameters and immune response in the fish species Hoplias malabaricus after trophic exposure. Fish were fed twice every week with Astyanax sp., which were given an intraperitoneal inoculation with diclofenac (0 μg/kg, 0.2 μg/kg, 2.0 μg/kg, or 20.0 μg/kg) or dexamethasone (0.03 μg/kg, 0.3 μg/kg, or 3.0 μg/kg). After 12 doses, the hematological parameters and lipopolysaccharide-induced nitric oxide production by head kidney monocytic lineage were evaluated. Exposed fish also received 1 mg/kg of carrageenan intraperitoneal, and cell migration to the peritoneal cavity was evaluated after 4 h. Diclofenac and dexamethasone altered the red blood cell count, as well as hematocrit and hemoglobin levels. The total blood leukocyte count decreased in all groups. A significantly reduced carrageenan-induced leukocyte migration to the peritoneal cavity, particularly of polymorphonuclear cells, was observed at all tested doses, suggesting a possible immunosuppressive effect. The basal nitric oxide synthesis of head kidney cell cultures was reduced at the highest dose of diclofenac and was increased at the highest dose of dexamethasone. The lipopolysaccharide-stimulated nitric oxide production was reduced in all treatments, thus corroborating the immunosuppressive effect. Although some fish responses were variable for different drugs, the results suggested that trophic exposure to diclofenac and dexamethasone can lead to hematological changes and immunotoxic effects, causing negative impacts in aquatic organisms. © 2015 SETAC.

  4. Effect of dexamethasone added to lidocaine in supraclavicular brachial plexus block: A prospective, randomised, double-blind study

    Directory of Open Access Journals (Sweden)

    Prashant A Biradar

    2013-01-01

    Full Text Available Background: Different additives have been used to prolong brachial plexus block. We performed a prospective, randomised, double-blind study to evaluate the effect of dexamethasone added to lidocaine on the onset and duration of supraclavicular brachial plexus block as this is the most common type of brachial block performed in our institute. Methods: Sixty American Society of Anaesthesiologist′s physical status I and II patients undergoing elective hand, forearm and elbow surgery under brachial plexus block were randomly allocated to receive either 1.5% lidocaine (7 mg/kg with adrenaline (1:200,000 and 2 ml of normal saline (group C, n=30 or 1.5% lidocaine (7 mg/kg with adrenaline (1:200,000 and 2 ml of dexamethasone (8 mg (group D, n=30. The block was performed using a nerve stimulator. Onset and duration of sensory and motor blockade were assessed. The sensory and motor blockade of radial, median, ulnar and musculocutaneous nerves were evaluated and recorded at 5, 10, 20, 120 min, and at every 30 min thereafter. Results: Two patients were excluded from the study because of block failure. The onset of sensory and motor blockade (13.4±2.8 vs. 16.0±2.3 min and 16.0±2.7 vs. 18.7±2.8 min, respectively were significantly more rapid in the dexamethasone group than in the control group ( P=0.001. The duration of sensory and motor blockade (326±58.6 vs. 159±20.1 and 290.6±52.7 vs. 135.5±20.3 min, respectively were significantly longer in the dexamethasone group than in the control group ( P=0.001. Conclusion: Addition of dexamethasone to 1.5% lidocaine with adrenaline in supraclavicular brachial plexus block speeds the onset and prolongs the duration of sensory and motor blockade.

  5. Dexamethasone Protects Against Tourniquet-Induced Acute Ischemia-Reperfusion Injury in Mouse Hindlimb

    Directory of Open Access Journals (Sweden)

    Ryan M. Corrick

    2018-03-01

    Full Text Available Extremity injuries with hemorrhage have been a significant cause of death in civilian medicine and on the battlefield. The use of a tourniquet as an intervention is necessary for treatment to an injured limb; however, the tourniquet and subsequent release results in serious acute ischemia-reperfusion (IR injury in the skeletal muscle and neuromuscular junction (NMJ. Much evidence demonstrates that inflammation is an important factor to cause acute IR injury. To find effective therapeutic interventions for tourniquet-induced acute IR injuries, our current study investigated effect of dexamethasone, an anti-inflammatory drug, on tourniquet-induced acute IR injury in mouse hindlimb. In C57/BL6 mice, a tourniquet was placed on unilateral hindlimb (left hindlimb at the hip joint for 3 h, and then released for 24 h to induce IR. Three hours of tourniquet and 24 h of release (24-h IR caused gastrocnemius muscle injuries including rupture of the muscle sarcolemma and necrosis (42.8 ± 2.3% for infarct size of the gastrocnemius muscle. In the NMJ, motor nerve terminals disappeared, and endplate potentials were undetectable in 24-h IR mice. There was no gastrocnemius muscle contraction in 24-h IR mice. Western blot data showed that inflammatory cytokines (TNFα and IL-1β were increased in the gastrocnemius muscle after 24-h IR. Treatment with dexamethasone at the beginning of reperfusion (1 mg/kg, i.p. significantly inhibited expression of TNFα and IL-1β, reduced rupture of the muscle sarcolemma and infarct size (24.8 ± 2.0%, and improved direct muscle stimulation-induced gastrocnemius muscle contraction in 24-h IR mice. However, this anti-inflammatory drug did not improve NMJ morphology and function, and sciatic nerve-stimulated skeletal muscle contraction in 24-h IR mice. The data suggest that one-time treatment with dexamethasone at the beginning of reperfusion only reduced structural and functional impairments of the skeletal muscle but not the

  6. Dexamethasone concentration gradients along scala tympani after application to the round window membrane.

    Science.gov (United States)

    Plontke, Stefan K; Biegner, Thorsten; Kammerer, Bernd; Delabar, Ursular; Salt, Alec N

    2008-04-01

    Local application of dexamethasone-21-dihydrogen-phosphate (Dex-P) to the round window (RW) membrane of guinea pigs produces a substantial basal-apical concentration gradient in scala tympani (ST) perilymph. In recent years, intratympanically applied glucocorticoids are increasingly being used for the treatment of inner ear disease. Although measurements of intracochlear concentrations after RW application exist, there is limited information on the distribution of these drugs in the inner ear fluids. It has been predicted from computer simulations that substantial concentration gradients will occur after RW application, with lower concentrations expected in apical turns. Concentration gradients of other substances along the cochlea have recently been confirmed using a sequential apical sampling method to obtain perilymph. Dexamethasone-21-dihydrogen-phosphate (10 mg/ml) was administered to the RW membrane of guinea pigs (n = 9) in vivo for 2 to 3 hours. Perilymph was then collected using a protocol in which 10 samples, each of approximately 1 mul, were taken sequentially from the cochlear apex into capillary tubes. Dexamethasone-21-dihydrogen-phosphate concentration of the samples was analyzed by high-performance liquid chromatography. Interpretation of sample data using a finite element model allowed the longitudinal gradients of Dex-P in ST to be quantified. The Dex-P content of the first sample in each experiment (dominated by perilymph from apical regions) was substantially lower than that of the third and fourth sample (dominated by basal turn perilymph). These findings qualitatively demonstrated the existence of a concentration gradient along ST. After detailed analysis of the measured sample concentrations using an established finite element computer model, the mean basal-apical concentration gradient was estimated to be 17,000. Both absolute concentrations of Dex-P in ST and the basal-apical gradients were found to vary substantially. The existence of

  7. Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration.

    Science.gov (United States)

    Hahn, Hartmut; Kammerer, Bernd; DiMauro, Andre; Salt, Alec N; Plontke, Stefan K

    2006-02-01

    Before new drugs for the treatment of inner ear disorders can be studied in controlled clinical trials, it is important that their pharmacokinetics be established in inner ear fluids. Microdialysis allows drug levels to be measured in perilymph without the volume disturbances and potential cerebrospinal fluid contamination associated with fluid sampling. The aims of this study were to show: (i) that despite low recovery rates from miniature dialysis probes, significant amounts of drug are removed from small fluid compartments, (ii) that dialysis sampling artifacts can be accounted for using computer simulations and (iii) that microdialysis allows quantification of the entry rates through the round window membrane (RWM) into scala tympani (ST). Initial experiments used microdialysis probes in small compartments in vitro containing sodium fluorescein. Stable concentrations were observed in large compartments (1000 microl) but significant concentration declines were observed in smaller compartments (100, 10 and 5.6 microl) comparable to the size of the inner ear. Computer simulations of these experiments closely approximated the experimental data. In in vivo experiments, sodium fluorescein 10 mg/ml and dexamethasone-dihydrogen-phosphate disodium salt 8 mg/ml were simultaneously applied to the RWM of guinea pigs. Perilymph concentration in the basal turn of ST was monitored using microdialysis. The fluorescein concentration reached after 200 min application (585+/-527 microg/ml) was approximately twice that of dexamethasone phosphate (291+/-369 microg/ml). Substantial variation in concentrations was found between animals by approximately a factor of 34 for fluorescein and at least 41 for dexamethasone phosphate. This is, to a large extent, thought to be the result of the RWM permeability varying in different animals. It was not caused by substance analysis variations, because two different analytic methods were used and the concentration ratio between the two

  8. Influence of dexamethasone and weight loss on the regulation of serum leptin levels in obese individuals

    Directory of Open Access Journals (Sweden)

    D.D.G. Lerario

    2001-04-01

    Full Text Available The adipocyte hormone leptin is thought to serve as a signal to the central nervous system reflecting the status of fat stores. Serum leptin levels and adipocyte leptin messenger RNA levels are clearly increased in obesity. Nevertheless, the factors regulating leptin production are not fully understood. The aim of this study was to determine the effects of in vivo administration of the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels in two independent protocols. Twenty-five obese subjects were studied (18 women and 7 men, mean age 26.6 ± 6 years, BMI 31.1 ± 2.5 kg/m², %fat 40.3 ± 8.3 and compared at baseline to 22 healthy individuals. Serum levels of leptin, insulin, proinsulin and glucose were assessed at baseline and after ingestion of dexamethasone, 4 mg per day (2 mg, twice daily for two consecutive days. To study the effects of weight loss on serum leptin, 17 of the obese subjects were submitted to a low-calorie dietary intervention trial for 8 weeks and again blood samples were collected. Serum leptin levels were significantly higher in the obese group compared to the control group and a high positive correlation between leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001. After dexamethasone, there was a significant increase in serum leptin levels (22.9 ± 12.3 vs 51.4 ± 23.3 ng/ml, P<0.05. Weight loss (86.1 ± 15.1 vs 80.6 ± 14.2 kg, P<0.05 led to a reduction in leptin levels (25.13 ± 12.8 vs 15.9 ± 9.1 ng/ml, P<0.05. We conclude that serum leptin levels are primordially dependent on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent secretagogues of leptin in obese subjects and a mild fat mass reduction leads to a disproportionate decrease in serum leptin levels. This suggests that, in addition to the changes in fat mass, complex nutritional and hormonal interactions may also play an important role in the regulation of leptin levels.

  9. Antenatal dexamethasone after asphyxia increases neural injury in preterm fetal sheep.

    Directory of Open Access Journals (Sweden)

    Miriam E Koome

    Full Text Available BACKGROUND AND PURPOSE: Maternal glucocorticoid treatment for threatened premature delivery dramatically improves neonatal survival and short-term morbidity; however, its effects on neurodevelopmental outcome are variable. We investigated the effect of maternal glucocorticoid exposure after acute asphyxia on injury in the preterm brain. METHODS: Chronically instrumented singleton fetal sheep at 0.7 of gestation received asphyxia induced by complete umbilical cord occlusion for 25 minutes. 15 minutes after release of occlusion, ewes received a 3 ml i.m. injection of either dexamethasone (12 mg, n = 10 or saline (n = 10. Sheep were killed after 7 days recovery; survival of neurons in the hippocampus and basal ganglia, and oligodendrocytes in periventricular white matter were assessed using an unbiased stereological approach. RESULTS: Maternal dexamethasone after asphyxia was associated with more severe loss of neurons in the hippocampus (CA3 regions, 290 ± 76 vs 484 ± 98 neurons/mm(2, mean ± SEM, P<0.05 and basal ganglia (putamen, 538 ± 112 vs 814 ± 34 neurons/mm(2, P<0.05 compared to asphyxia-saline, and with greater loss of both total (913 ± 77 vs 1201 ± 75/mm(2, P<0.05 and immature/mature myelinating oligodendrocytes in periventricular white matter (66 ± 8 vs 114 ± 12/mm(2, P<0.05, vs sham controls 165 ± 10/mm(2, P<0.001. This was associated with transient hyperglycemia (peak 3.5 ± 0.2 vs. 1.4 ± 0.2 mmol/L at 6 h, P<0.05 and reduced suppression of EEG power in the first 24 h after occlusion (maximum -1.5 ± 1.2 dB vs. -5.0 ± 1.4 dB in saline controls, P<0.01, but later onset and fewer overt seizures. CONCLUSIONS: In preterm fetal sheep, exposure to maternal dexamethasone during recovery from asphyxia exacerbated brain damage.

  10. Dexamethasone Injection

    Science.gov (United States)

    ... staying asleep extreme changes in mood changes in personality depression increased sweating muscle weakness joint pain irregular ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  11. Haloperidol dose combined with dexamethasone for PONV prophylaxis in high-risk patients undergoing gynecological laparoscopic surgery: a prospective, randomized, double-blind, dose-response and placebo-controlled study.

    Science.gov (United States)

    Joo, Jin; Park, Yong Gyu; Baek, Jungwon; Moon, Young Eun

    2015-07-08

    Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. Female adults (n = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0-2 h) and late (2-24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; P = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (P haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. ClinicalTrials.gov ( NCT01639599 ).

  12. Metabolism of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136) Atropisomers in Tissue Slices from Phenobarbital or Dexamethasone-Induced Rats is Sex-Dependent

    Science.gov (United States)

    Wu, Xianai; Kania-Korwel, Izabela; Chen, Hao; Stamou, Marianna; Dammanahalli, Karigowda J.; Duffel, Michael; Lein, Pamela J.; Lehmler, Hans-Joachim

    2013-01-01

    Chiral polychlorinated biphenyls (PCBs) such as PCB 136 enantioselectively sensitize the ryanodine receptor (RyR). In light of recent evidence that PCBs cause developmental neurotoxicity via RyR-dependent mechanisms, this suggests that enantioselective PCB metabolism may influence the developmental neurotoxicity of chiral PCBs. However, enantioselective disposition of PCBs has not been fully characterized.The effect of sex and cytochrome P450 (P450) enzyme induction on the enantioselective metabolism of PCB 136 was studied using liver tissue slices prepared from naïve control (CTL), phenobarbital (PB; CYP2B inducer) or dexamethasone (DEX; CYP3A inducer) pretreated adult Sprague-Dawley rats. PCB 136 metabolism was also examined in hippocampal slices derived from untreated rat pups.In liver tissue slices, hydroxylated PCB (OH-PCB) profiles depended on sex and inducer pretreatment, and OH-PCB levels followed the rank orders male > female and PB > DEX > CTL. In contrast, the enantiomeric enrichment of PCB 136 and its metabolites was independent of sex and inducer pretreatment. Only small amounts of PCB 136 partitioned into hippocampal tissue slices and no OH-PCB metabolites were detected.Our results suggest that enantioselective metabolism, sex and induction status of P450 enzymes in the liver may modulate the neurotoxic outcomes of developmental exposure to chiral PCBs. PMID:23581876

  13. Vector control of induction machines

    CERN Document Server

    Robyns, Benoit

    2012-01-01

    After a brief introduction to the main law of physics and fundamental concepts inherent in electromechanical conversion, ""Vector Control of Induction Machines"" introduces the standard mathematical models for induction machines - whichever rotor technology is used - as well as several squirrel-cage induction machine vector-control strategies. The use of causal ordering graphs allows systematization of the design stage, as well as standardization of the structure of control devices. ""Vector Control of Induction Machines"" suggests a unique approach aimed at reducing parameter sensitivity for

  14. Borehole induction coil transmitter

    Science.gov (United States)

    Holladay, Gale; Wilt, Michael J.

    2002-01-01

    A borehole induction coil transmitter which is a part of a cross-borehole electromagnetic field system that is used for underground imaging applications. The transmitter consists of four major parts: 1) a wound ferrite or mu-metal core, 2) an array of tuning capacitors, 3) a current driver circuit board, and 4) a flux monitor. The core is wound with several hundred turns of wire and connected in series with the capacitor array, to produce a tuned coil. This tuned coil uses internal circuitry to generate sinusoidal signals that are transmitted through the earth to a receiver coil in another borehole. The transmitter can operate at frequencies from 1-200 kHz and supplies sufficient power to permit the field system to operate in boreholes separated by up to 400 meters.

  15. Inductive circuit arrangements

    International Nuclear Information System (INIS)

    Mansfield, Peter; Coxon, R.J.

    1987-01-01

    A switched coil arrangement is connected in a bridge configuration of four switches S 1 , S 2 , S 3 and S 4 which are each shunted by diodes D 1 , D 2 , D 3 and D 4 so that current can flow in either direction through a coil L depending on the setting of the switches. A capacitor C is connected across the bridge through a switch S 5 to receive the inductive energy stored in coil L on breaking the current flow path through the coil. The electrostatic energy stored in capacitor C can then be used to supply current through the coil in the reverse direction either immediately or after a time delay. Coil L may be a superconductive coil. Losses in the circuit can be made up by a trickle charge of capacitor C from a separate supply V 2 . The device may be used in nuclear magnetic resonance imaging. (author)

  16. Induction heating using induction coils in series-parallel circuits

    Science.gov (United States)

    Matsen, Marc Rollo; Geren, William Preston; Miller, Robert James; Negley, Mark Alan; Dykstra, William Chet

    2017-11-14

    A part is inductively heated by multiple, self-regulating induction coil circuits having susceptors, coupled together in parallel and in series with an AC power supply. Each of the circuits includes a tuning capacitor that tunes the circuit to resonate at the frequency of AC power supply.

  17. The effect of dexamethasone on thyrocytes from patients with Graves' disease

    International Nuclear Information System (INIS)

    Zhao Yaping; Wang Jialin

    2002-01-01

    To investigate the effect of dexamethasone (DEX) on thyrocytes of patients with Graves' Disease (GD), thyrocytes from GD were cultured in the presence of 10 -6 -10 -2 mol/L DEX. the growth of thyrocyte was measured by MTT method. Apoptosis, Fas expression were detected by Tunnel method and S-P method respectively. The result showed that 1) DEX in 10 -6 -10 -2 mol/L could kill the thyrocytes directly in time dependently. 2) Apoptosis and fas expression of thyrocyte cultured with DEX were significantly increased. 3) The rate of apoptosis was positively correlated with Fas expressions level. This results suggest that DEX can regulate the functions of thyroid by killing thyrocytes directly and inducing thyroid apoptosis

  18. Accidental injections of dexamethasone intravitreal implant (Ozurdex) into the crystalline lens.

    Science.gov (United States)

    Coca-Robinot, Javier; Casco-Silva, Bruno; Armadá-Maresca, Felix; García-Martínez, Jesús

    2014-01-01

    To describe the side effects and management after inadvertent injection of a dexamethasone implant (Ozurdex) into the crystalline lens. Two case reports. Two patients with macular edema due to unilateral retinal vein occlusion were scheduled for an intravitreal injection of Ozurdex. During the procedure, the implant was accidentally injected into the crystalline lens. Both patients developed cataracts during the course of several weeks and in both there was an intraocular pressure (IOP) increase, which required treatment with topical hypotensives. Macular edema improved only slightly. Cataract surgery with uneventful removal of the implant was performed 3 (case 1) and 6 months (case 2) after the injection. After inadvertent injection of Ozurdex into the crystalline lens, cataract surgery with removal of the implant should be performed as soon as possible in order to avoid IOP increase and so that the underlying condition may be treated adequately.

  19. Prenatal stress may increase vulnerability to life events comparison with the effects of prenatal dexamethasone

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Kjaer, Sanna L

    2005-01-01

    naïve at the time of ASR testing, whereas the other had been through blood sampling for assessment of the hormonal stress response to restraint, 3 months previously. Both prenatal CMS and dexamethasone increased ASR in the offspring compared to controls, but only in prenatally stressed offspring......Prenatal stress has been associated with a variety of alterations in the offspring. The presented observations suggest that rather than causing changes in the offspring per se, prenatal stress may increase the organism's vulnerability to aversive life events. Offspring of rat dams stressed...... of the acoustic startle response. Further, a single aversive life event showed capable of changing the reactivity of prenatally stressed offspring, whereas offspring of dams going through a less stressful gestation was largely unaffected by this event. This suggests that circumstances dating back to the very...

  20. Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion

    DEFF Research Database (Denmark)

    Falchi, Mario; Varricchio, Lilian; Martelli, Fabrizio

    2015-01-01

    Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages...... in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169(pos) macrophages established multiple rapid 'loose' interactions...... with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169(neg) macrophages established 'tight' interactions with mature erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos) macrophages were associated with proerythroblast cytokinesis (the...

  1. Dexamethasone, BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Henriksen, Z; Sørensen, O H

    2004-01-01

    . Osteoblast phenotypes were induced by either dexamethasone (Dex) or bone morphogenetic protein-2 (BMP-2). Bone marrow was obtained from biopsies at the posterior iliac spine. Cells were isolated by gradient centrifugation and grown to confluence. Cells were treated with 1 nM 1,25-dihydroxyvitamin D (vitamin...... activity was increased by Dex, but not by BMP-2 treatment. P1NP production was decreased after Dex treatment, while BMP-2 had no effect on P1NP levels. Osteocalcin production was low in cultures not stimulated with vitamin D. Dex or BMP-2 treatment alone did not affect the basic osteocalcin levels......, but in combination with vitamin D, BMP-2 increased the osteocalcin production, while Dex treatment completely suppressed osteocalcin production. Further, PTH-induced cAMP production was greatly enhanced by Dex treatment, whereas BMP-2 did not affect cAMP production. Finally, in vitro mineralization was greatly...

  2. Neonatal dexamethasone accelerates spreading depression in the rat, and antioxidant vitamins counteract this effect.

    Science.gov (United States)

    Lopes-de-Morais, Andréia Albuquerque Cunha; Mendes-da-Silva, Rosângela Figueiredo; dos-Santos, Eryka Maria; Guedes, Rubem Carlos Araújo

    2014-12-03

    The use of dexamethasone (Dex) to treat chronic lung disease in preterm infants may produce adverse effects in the developing brain. Here, we evaluated the effects of neonatal Dex on the propagation of cortical spreading depression (CSD), and tested the action of vitamins C and E against the effect of Dex. Five groups of Wistar rats received, respectively: [1] no treatment (Naïve); [2] Vehicle (V); [3] tapering doses of Dex (Dex; 0.5mg/kg, 0.3mg/kg, and 0.1mg/kg) on postnatal day (PND) 1-3; [4] Dex plus 200mg/kg vitamin C and 100mg/kg vitamin E (DexCE); [5] only vitamins C and E (CE). Vehicle and vitamins were administered on PND 1-6. CSD was recorded after the pups reached maturity (PND 60-70). The Dex-treated group presented with higher CSD velocities (mean values ± SD, in mm/min: 4.14 ± 0.22, n=10) compared with the control groups (Naïve: 3.52 ± 0.13, n=8; V: 3.57 ± 0.18, n=10; CE: 3.51 ± 0.24, n=10; pVitamins C and E antagonized this effect (DexCE group; CSD velocity: 3.43 ± 0.12, n=9). No intergroup difference was observed concerning P-wave amplitude and duration. In all groups, after the cortex underwent CSD, the electrocorticogram (ECoG) amplitude increased approximately 50% compared with the baseline amplitude for the same animal (CSD-induced ECoG potentiation); however, no intergroup difference was observed. Data suggest that coadministration of antioxidant vitamins with Dex may be a helpful therapeutic strategy to reduce brain adverse effects of dexamethasone. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. The combined dexamethasone/TSST paradigm--a new method for psychoneuroendocrinology.

    Directory of Open Access Journals (Sweden)

    Julie Andrews

    Full Text Available The two main physiological systems involved in the regulation of the stress response are the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system (SNS. However, the interaction of these systems on the stress response remains poorly understood. To better understand the cross-regulatory effects of the different systems involved in stress regulation, we developed a new stress paradigm that keeps the activity of the HPA constant when exposing subjects to psychosocial stress. Thirty healthy male participants were recruited and randomly assigned to either a dexamethasone (DEX; n = 15 or placebo (PLC; n = 15 group. All subjects were instructed to take the Dexamethasone (2 mg or Placebo pill the night before coming to the laboratory to undergo the Trier Social Stress Task (TSST. Salivary cortisol, salivary alpha amylase (sAA, heart rate, blood pressure and subjective stress were assessed throughout the protocol. As expected, the DEX group presented with suppressed cortisol levels. In comparison, their heart rate was elevated by approximately ten base points compared to the PLC group, with increases throughout the protocol and during the TSST. Neither sAA, nor systolic or diastolic blood pressures showed significant group differences. Subjective stress levels significantly increased from baseline, and were found to be higher before and after the TSST after DEX compared to placebo. These results demonstrate a significant interaction between the HPA and the SNS during acute stress. The SNS activity was found to be elevated in the presence of a suppressed HPA axis, with some further effects on subjective levels of stress. The method to suppress the HPA prior to inducing stress was found to completely reliable, without any adverse side effects. Therefore, we propose this paradigm as a new method to investigate the interaction of the two major stress systems in the regulation of the stress response.

  4. Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits

    Directory of Open Access Journals (Sweden)

    Linhua Zhang

    2009-09-01

    Full Text Available Linhua Zhang1, Yue Li2, Chao Zhang1, Yusheng Wang2, Cunxian Song11Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China; 2Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaAbstract: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX-loaded poly(lactic acid–co-glycolic acid nanoparticles (DEX-NPs in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L-1. Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.Keywords: dexamethasone, nanoparticles, intravitreal injection, pharmacokinetics

  5. Comparison of Local Anesthetic Effect of Bupivacaine versus Bupivacaine plus Dexamethasone in Nasal Surgery

    Directory of Open Access Journals (Sweden)

    Abdolhosein Ma’somi

    2012-12-01

    Full Text Available   Introduction: Adequate pain control is an important consideration in the post-surgical management of patients. Local nerve blockade added to general anesthesia can provide excellent pain control during and after most nasal surgical procedures. The aim of this study was to determine the combined effect of local anesthetic drugs with corticosteroids in nasal surgery. Materials and Methods: In this double-blind clinical study, 60 patients who underwent different nasal surgical procedures were matched and divided into two equal groups. Bilateral local nerve blockade was used in both groups. Bupivacaine or bupivacaine plus dexamethasone was administered by injection (groups B and B+D, respectively. Postoperative visual analog scale (VAS pain values and the need for oral/intramuscular analgesic treatment in the first 24 h were recorded in all patients. Results: Thirty-eight male (63.3% and 22 female (36.7% patients were included in this study, with a mean age of 28.3 ± 8.2 years. At 1, 2, 4, 6, and 12 h post surgery, VAS pain values were significantly lower in the B+D group than in the B group. The analgesic requirement was significantly lower in the B+D group compared with the B group. No relevant complications were seen during surgery or postoperative hospitalization. Conclusion: This study demonstrates the positive effect of a combination of a dexamethasone with a bupivacaine in reducing pain and the need for analgesic drugs after different nasal surgeries. No acute or short-term post-surgical complications were observed in this study.   

  6. Dexamethasone Drug Eluting Nanowafers Control Inflammation in Alkali-Burned Corneas Associated With Dry Eye

    Science.gov (United States)

    Bian, Fang; Shin, Crystal S.; Wang, Changjun; Pflugfelder, Stephen C.; Acharya, Ghanashyam; De Paiva, Cintia S.

    2016-01-01

    Purpose To evaluate the efficacy of a controlled release dexamethasone delivery system for suppressing inflammation in an ocular burn + desiccating stress (OB+DS) model. Methods Nanowafers (NW) loaded with Dexamethasone (Dex, 10 μg) or vehicles (2.5% Methylcellulose; MC) were fabricated using hydrogel template strategy. C57BL/6 mice were subjected to unilateral alkali ocular burn with concomitant desiccating stress for 2 or 5 days and topically treated either with 2 μL of 0.1% Dex or vehicle four times per day and compared with mice that had MC-NW or Dex-NW placed on their corneas. Clinical parameters were evaluated daily. Mice were euthanized after 2 or 5 days. Quantitative PCR evaluated the expression of inflammatory cytokines IL-1β and IL-6 and matrix metalloproteinases (MMP) in whole cornea lysates. Myeloperoxidase activity (MPO) was measured using a commercial kit in cornea lysates. Results Both Dex drop and Dex-NW groups had significantly lower corneal opacity scores compared with their vehicles. Both Dex drops and Dex-NW significantly decreased expression of IL-1β, IL-6, and MMP-9 RNA transcripts compared with vehicle drops or wafers 2 and 5 days after the initial lesion. A significant lower number of neutrophils was found in both Dex treatment groups and this was accompanied by decreased MPO activity compared with vehicle controls. Conclusions Dex-NW has efficacy equal to Dex drops in preserving corneal clarity and decreasing expression of MMPs and inflammatory cytokines of the corneas of mice subjected to an OB+DS model. PMID:27327581

  7. Dexamethasone-Induced Myeloid-Derived Suppressor Cells Prolong Allo Cardiac Graft Survival through iNOS- and Glucocorticoid Receptor-Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Yang Zhao

    2018-02-01

    Full Text Available How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro. However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance. Herein, we combined dexamethasone (Dex, which is a classic immune regulatory drug in the clinic, with common MDSCs inducing cytokine granulocyte macrophage colony stimulating factor (GM-CSF to generate MDSCs in vitro. Addition of Dex into GM-CSF system specifically increased the number of CD11b+ Gr-1int/low MDSCs with an enhanced immunosuppressive function in vitro. Adoptive transfer of these MDSCs significantly prolonged heart allograft survival and also favored the expansion of regulatory T cells in vivo. Mechanistic studies showed that inducible nitric oxide sythase (iNOS signaling was required for MDSCs in the control of T-cell response and glucocorticoid receptor (GR signaling played a critical role in the recruitment of transferred MDSCs into allograft through upregulating CXCR2 expression on MDSCs. Blockade of GR signaling with its specific inhibitor or genetic deletion of iNOS reversed the protective effect of Dex-induced MDSCs on allograft rejection. Together, our results indicated that co-application of Dex and GM-CSF may be a new and important strategy for the induction of potent MDSCs to achieve immune tolerance in organ transplantation.

  8. Effect of intravenous magnesium sulphate or dexamethasone as adjuvants to sevoflurane anesthesia to prevent delirium during primary cleft palate repair, controlled randomized blind study

    Directory of Open Access Journals (Sweden)

    M. Elsonbaty

    2017-01-01

    Conclusion: Co-administration of intravenous magnesium sulphate or dexamethasone with to sevoflurane anesthesia during primary cleft palate repair provides more vital hemodynamic state and decrease in postoperative vomiting and delirium when compared with control group.

  9. Probabilistic inductive inference: a survey

    OpenAIRE

    Ambainis, Andris

    2001-01-01

    Inductive inference is a recursion-theoretic theory of learning, first developed by E. M. Gold (1967). This paper surveys developments in probabilistic inductive inference. We mainly focus on finite inference of recursive functions, since this simple paradigm has produced the most interesting (and most complex) results.

  10. A Student Teamwork Induction Protocol

    Science.gov (United States)

    Kamau, Caroline; Spong, Abigail

    2015-01-01

    Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in higher education. This naturalistic experiment compared a control cohort with an inducted cohort. The inducted cohort attended a workshop, consultations, elected a leader and used tools (a group log and group…

  11. Sampling Assumptions in Inductive Generalization

    Science.gov (United States)

    Navarro, Daniel J.; Dry, Matthew J.; Lee, Michael D.

    2012-01-01

    Inductive generalization, where people go beyond the data provided, is a basic cognitive capability, and it underpins theoretical accounts of learning, categorization, and decision making. To complete the inductive leap needed for generalization, people must make a key "sampling" assumption about how the available data were generated.…

  12. From Inductive Reasoning to Proof

    Science.gov (United States)

    Yopp, David A.

    2009-01-01

    Mathematical proof is an expression of deductive reasoning (drawing conclusions from previous assertions). However, it is often inductive reasoning (conclusions drawn on the basis of examples) that helps learners form their deductive arguments, or proof. In addition, not all inductive arguments generate more formal arguments. This article draws a…

  13. Covariation in Natural Causal Induction.

    Science.gov (United States)

    Cheng, Patricia W.; Novick, Laura R.

    1991-01-01

    Biases and models usually offered by cognitive and social psychology and by philosophy to explain causal induction are evaluated with respect to focal sets (contextually determined sets of events over which covariation is computed). A probabilistic contrast model is proposed as underlying covariation computation in natural causal induction. (SLD)

  14. Economic implications of labor induction.

    Science.gov (United States)

    Garcia-Simon, Raquel; Montañes, Antonio; Clemente, Jesús; Del Pino, María D; Romero, Manuel A; Fabre, Ernesto; Oros, Daniel

    2016-04-01

    To assess health service costs associated with labor induction according to different clinical situations in a tertiary-level hospital. In a prospective study, individual patient cost data were assessed for women admitted for induction of labor at a tertiary hospital in Spain between November 1, 2012, and August 31, 2013. The costs of labor induction were estimated according to maternal and neonatal outcomes, method of delivery, cervical condition at admission, and obstetric indication. Direct costs including professional fees, epidural, maternal stay, consumables, and drugs were calculated. Overall, 412 women were included in the final cost analysis. The mean total cost of labor induction was €3589.87 (95% confidence interval [CI] 3475.13-3704.61). Cesarean delivery after labor induction (€4830.45, 95% CI 4623.13-5037.58) was significantly more expensive than spontaneous delivery (€3037.45, 95% CI 2966.91-3179.99) and instrumental vaginal delivery (€3344.31, 95%CI 3151.69-3536.93). The total cost for patients with a very unfavorable cervix (Bishop score Labor induction for hypertensive disorders of pregnancy was the most expensive obstetric indication for induction of labor (€4347.32, 95% CI 3890.45-4804.18). Following the induction of labor, a number of patient- and treatment-related factors influence costs associated with delivery. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Efficacy of palonosetron and 1-day dexamethasone in moderately emetogenic chemotherapy compared with fosaprepitant, granisetron, and dexamethasone: a prospective randomized crossover study.

    Science.gov (United States)

    Kitayama, Hiromitsu; Tsuji, Yasushi; Sugiyama, Junko; Doi, Ayako; Kondo, Tomohiro; Hirayama, Michiaki

    2015-12-01

    Although palonosetron (PALO) and NK1 receptor antagonist both reduce chemotherapy-induced nausea and vomiting, no comparison trial in moderately emetogenic chemotherapy (MEC) had been reported. The purpose of this study was to find out which drug combinations are preferable for patients receiving MEC. Chemotherapy-naive patients receiving MEC were randomized to two groups; group A first received PALO therapy [PALO plus 1-day dexamethasone (DEX)], and group B first received fosaprepitant (FAPR) therapy [FAPR, granisetron (GRAN), and DEX]. Patients were re-allocated to the other therapy, respectively, for the second cycle of chemotherapy. We administered intravenous PALO (0.75 mg) and DEX (9.9 mg) to the PALO therapy group, and FAPR (150 mg), DEX (4.95 mg), and GRAN (3 mg) to the FAPR therapy group, on Day 1. Complete response (CR) was the primary endpoint; complete control (CC), total control (CT), and the therapy chosen by the patients for their third and following cycles of antiemetic therapy were the secondary endpoints. We evaluated CR, CC, and TC in the acute phase, in the delayed phase, and over the whole period. A total of 35 patients and 70 cycles of therapy was evaluable for analysis. No significant difference was found at all evaluation points. Overall CR rates for PALO and FAPR therapy were 74 vs 69 % (P = 0.567), CC rates 66 vs 69 % (P = 0.521), and TC rates 46 vs 60 % (P = 0.235), respectively. Patients also showed no clear preference for their third and following cycles of chemotherapy, choosing both regimens almost equally often (PALO 10 vs FAPR 13). PALO and 1-day DEX is almost equivalent to FAPR, GRAN, and DEX for MEC.

  16. Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria

    OpenAIRE

    Yahi, Dauda; Ojo, Nicholas Adetayo; Mshelia, Gideon Dauda

    2017-01-01

    Dexamethasone is widely used in both veterinary and human medical practices. However, it seems to cause some deleterious effects on pregnancy probably by causing changes in the reproductive hormone levels and their corresponding receptor concentrations. This study investigated the effects of dexamethasone on these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after estrus synchronization. Dexa...

  17. Identification of cysteine-644 as the covalent site of attachment of dexamethasone 21-mesylate to murine glucocorticoid receptors in WEHI-7 cells

    International Nuclear Information System (INIS)

    Smith, L.I.; Bodwell, J.E.; Mendel, D.B.; Ciardelli, T.; North, W.G.; Munck, A.

    1988-01-01

    Dexamethasone 21-mesylate is a highly specific synthetic glucocorticoid derivative that binds covalently to glucocorticoid receptors via sulfhydryl groups. The authors have identified the amino acid that reacts with the dexamethasone 21-mesylate by using enzymatic digestion and microsequencing for radiolabel. Nonactivated glucocorticoid receptors obtained from labeling intact WEHI-7 mouse thymoma cells with [ 3 H]dexamethasone 21-mesylate were immunopurified and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Trypsin digestion followed by reversed-phase high-performance liquid chromatography (reversed-phase HPLC) produced a single [ 3 H]dexamethasone 21-mesylate labeled peptide. Automated Edman degradation of this peptide revealed that the [ 3 H]dexamethasone 21-mesylate was located at position 5 from the amino terminus. Dual-isotope labeling studies with [ 3 H]dexamethasone 21-mesylate and [ 35 S]methionine demonstrated that this peptide contained methionine. Staphylococcus aureus V8 protease digestion of [ 3 H]dexamethasone 21-mesylate labeled steroid-binding subunits generated a different radiolabeled peptide containing label at position 7 from the amino terminus. On the basis of the published amino acid sequence of the murine glucocorticoid receptor, their data clearly identify cysteine-644 as the single residue in the steroid-binding domain that covalently binds dexamethasone 21-mesylate. They have confirmed this finding by demonstrating that a synthetic peptide representing the amino acid sequence 640-650 of the murine glucocorticoid receptor behaves in an identical manner on reversed-phase HPLC as the trypsin-generated peptide from intact cells

  18. The effect of dexamethasone on the radiation survival response and misonidazole-induced hypoxic-cell cytotoxicity in Chinese hamster cells V-79-753B in vitro

    International Nuclear Information System (INIS)

    Millar, B.C.; Jinks, S.

    1981-01-01

    Overnight exposure of Chinese hamster cells, V-79-753B, to microgram quantities of the synthetic corticosteroid, dexamethasone, resulted in a decrease in sensitivity towards radiation, both in air and in hypoxia. The effect was dose-modifying and the oxygen enhancement ratio did not change appreciably. Similarly, when dexamethasone-treated hypoxic cells were irradiated in the presence of misonidazole, a hypoxic cell radiosensitizer, there was a decrease in radiation sensitivity compared with untreated hypoxic cells irradiated with misonidazole. (author)

  19. The effects of dexamethasone (DXM) and vitamin A on the growth and metamorphosis of gamma irradiated, thyroxine induced Bufo melanostictus tadpoles

    International Nuclear Information System (INIS)

    Ahmad, M.; Haider, N.; Siddiqui, R.Q.R.

    1980-01-01

    This study deals with the effects of vitamin A and dexamethasone (DXM) on the metamorphosis of irradiated tadpoles. Results indicate that hypervitaminosis A depresses the metamorphosing action of thyroxine for several days. On the contrary, dexamethasone accelerates the action of exogenous thyroxine on tadpoles. Thus present data suggest that DXM supresses STH synthesis and promotes TSH secretion. Moreover, muscle appears to be its target tissue and DXM seems to promote the proteolytic digestion of the larval tail. (author)

  20. The Chondrogenic Induction Potential for Bone Marrow-Derived Stem Cells between Autologous Platelet-Rich Plasma and Common Chondrogenic Induction Agents: A Preliminary Comparative Study

    Directory of Open Access Journals (Sweden)

    Shan-zheng Wang

    2015-01-01

    Full Text Available The interests in platelet-rich plasma (PRP and their application in stem cell therapy have contributed to a better understanding of the basic biology of the prochondrogenesis effect on bone marrow-derived stem cells (BMSCs. We aimed at comparing the effect of autologous PRP with common chondrogenic induction agents (CCIAs on the chondrogenic differentiation of BMSCs. Rabbit BMSCs were isolated and characterized by flow cytometry and differentiated towards adipocytes and osteoblasts. The chondrogenic response of BMSCs to autologous PRP and CCIAs which included transforming growth factor-β1 (TGF-β1, dexamethasone (DEX, and vitamin C (Vc was examined by cell pellet culture. The isolated BMSCs after two passages highly expressed CD29 and CD44 but minimally expressed CD45. The osteogenic and adipogenic differentiation potentials of the isolated BMSCs were also confirmed. Compared with common CCIAs, autologous PRP significantly upregulated the chondrogenic related gene expression, including Col-2, AGC, and Sox-9. Osteogenic related gene expression, including Col-1 and OCN, was not of statistical significance between these two groups. Thus, our data shows that, compared with common chondrogenic induction agents, autologous PRP can be more effective in promoting the chondrogenesis of BMSCs.

  1. The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children.

    Science.gov (United States)

    Gnatzy, Richard; Hempel, Gunther; Kaisers, Udo X; Höhne, Claudia

    2015-11-01

    The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, pBlood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

  2. Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and IV Dexamethasone on Postoperative Sore Throat: A Randomized Controlled Trial.

    Science.gov (United States)

    Tabari, Masumeh; Soltani, Ghasem; Zirak, Nahid; Alipour, Moammad; Khazaeni, Kamran

    2013-09-01

    Postoperative sore throat is a common complaint in patients with endotracheal intubation and has potentially dangerous complications. This randomized controlled trial study investigated the incidence of postoperative sore throat after general anesthesia when betamethasone gel is applied to a tracheal tube compared with when IV dexamethasone is prescribed. Two hundred and twenty five American Society of Anesthesiologist (ASA)-class I and II patients undergoing elective abdominal surgery with tracheal intubation were randomly divided into three groups: betamethasone gel, intravenous (IV) dexamethasone, and control groups. In the post-anesthesia care unit, a blinded anesthesiologist interviewed all patients regarding postoperative sore throat at 1,6, and 24 hours after surgery. The incidence of sore throat was significantly lower in the betamethasone gel group compared with the IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the first day after surgery 10.7% of the betamethasone group had sore throat whereas 26.7% of the IV dexamethasone group and 30.7% of the control group had sore throat. Bucking before extubation was observed in 14(18.4%), 8(10.4%), and 9(12.2%) patients, in the IV dexamethasone, betamethasone gel, and control group, respectively. We concluded that wide spread application of betamethasone gel over tracheal tubes effectively mitigates postoperative sore throat, compared with IV dexamethasone application.

  3. Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and IV Dexamethasone on Postoperative sore Throat: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Masoomeh Tabari

    2013-10-01

    Full Text Available Introduction: Postoperative sore throat is a common complaint in patients with endotracheal intubation and has potentially dangerous complications. This randomized controlled trial study investigated the incidence of postoperative sore throat after general anesthesia when betamethasone gel is applied to a tracheal tube compared with when IV dexamethasone is prescribed.   Materials and Methods: Two hundred and twenty five American Society of Anesthesiologist (ASA-class I and II patients undergoing elective abdominal surgery with tracheal intubation were randomly divided into three groups: betamethasone gel, intravenous (IV dexamethasone, and control groups. In the post-anesthesia care unit, a blinded anesthesiologist interviewed all patients regarding postoperative sore throat at 1,6, and 24 hours after surgery.   Results: The incidence of sore throat was significantly lower in the betamethasone gel group compared with the IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the first day after surgery 10.7% of the betamethasone group had sore throat whereas 26.7% of the IV dexamethasone group and 30.7% of the control group had sore throat. Bucking before extubation was observed in 14(18.4%, 8(10.4%, and 9(12.2% patients, in the IV dexamethasone, betamethasone gel, and control group, respectively.   Conclusion:  We concluded that wide spread application of betamethasone gel over tracheal tubes effectively mitigates postoperative sore throat, compared with IV dexamethasone application.

  4. A randomized clinical trial to compare the efficacy of submucosal aprotinin injection and intravenous dexamethasone in reducing pain and swelling after third molar surgery: a prospective study.

    Science.gov (United States)

    Arakeri, Gururaj; Rai, Kirthi Kumar; Shivakumar, H R; Jayade, Bhushan

    2013-03-01

    The purpose of this study was to compare two different groups of drugs, aprotinin and dexamethasone for its efficacy in reducing post operative swelling and pain after third molar su