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Sample records for oral agent combination

  1. Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

    Science.gov (United States)

    Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

    2016-02-01

    Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

  2. Efficacy and safety of empagliflozin in combination with other oral hypoglycemic agents in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Romera, Irene; Ampudia-Blasco, Francisco Javier; Pérez, Antonio; Ariño, Bernat; Pfarr, Egon; Giljanovic Kis, Sanja; Naderali, Ebrahim

    2016-12-01

    To analyze the efficacy and safety of empagliflozin combined with other oral hypoglycemic agents in patients with type 2 diabetes mellitus. Pooled analysis of three phase III trials in patients with type 2 diabetes mellitus (n=1,801) who received placebo or empagliflozin 10 or 25mg once daily for 24 weeks, in combination with metformin, metformin+sulphonylurea or pioglitazone ± metformin. Empagliflozin significantly decreased HbA1c (adjusted mean reduction vs placebo with empagliflozin 10mg: -0.58% [95% CI: -0.66; -0.49]; P<.0001, and with empagliflozin 25mg: -0.62% [95% CI: -0.70; -0.53], P<.0001), weight (adjusted mean reduction vs placebo with empagliflozin 10mg: -1.77kg [95% CI: -2.05; -1.48]; P<.0001, and with empagliflozin 25mg: -1.96kg [95% CI: -2.24; -1.67], P<.0001), and systolic and diastolic blood pressure (SBP/DBP). Adverse effect rates were 64% with placebo, 63.9% with empagliflozin 10mg, and 60.9% with empagliflozin 25mg. Documented episodes of hypoglycemia (≤70mg/dL and/or requiring care) occurred in 3.9% of patients with placebo, 6.9% of patients with empagliflozin 10mg, and 5.3% of patients with empagliflozin 25mg. Urinary tract infections developed in 9.4% of patients with placebo, 10.2% of patients with empagliflozin 10mg, and 8.3% of patients with empagliflozin 25mg. Genital infections were reported in 1.0% of patients with placebo, 4.6% of patients with empagliflozin 10mg, and 3.5% of patients with empagliflozin 25mg. Empagliflozin combined with other oral treatments decreased HbA1c, body weight, and SBP/DBP as compared to placebo, with a good safety and tolerability profile. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

    2017-08-01

    Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

  4. Management of symptomatic erosive-ulcerative lesions of oral lichen planus in an adult Egyptian population using Selenium-ACE combined with topical corticosteroids plus antifungal agent

    Science.gov (United States)

    Belal, Mahmoud Helmy

    2015-01-01

    Aim: Oral lichen planus (OLP) is a chronic mucocutaneous disease with an immunological etiology. This study was conducted to evaluate the effect of selenium combined with Vitamins A, C & E (Selenium-ACE) in the treatment of erosive-ulcerative OLP as an adjunctive to topical corticosteroids plus antifungal agent. Subjects and Methods: Thirty patients with a confirmed clinical and histopathologic diagnosis of OLP participated in this clinical trial. Patients were randomly allocated into one of three groups and treated as follows: (I) Topical corticosteroids, (II) topical corticosteroids plus antifungal, and (III) SE-ACE combined with topical corticosteroids plus antifungal. The patients were followed for 6 weeks. The pain and severity of the lesions were recorded at the initial and follow-up visits. All recorded data were analyzed using paired t-test and ANOVA test. A P ≤ 0.05 was considered significant. Results: The experimental groups showed a marked reduction in pain sensation and size of lesions, particularly in the final follow-up period, but there was no significant difference between the first two Groups I and II. However, healing of lesions and improvement of pain sensation was effective in Group III since a significant difference was found favoring Group III over both Groups I and II. Conclusion: No significant difference was found in treating erosive-ulcerative lesions of OLP by topical corticosteroids alone or combined with antifungal. However, when using SE-ACE in combination with topical corticosteroids plus antifungal, this approach may be effective in managing ulcerative lesions of OLP; but more research with a larger sample size and a longer evaluation period may be recommended. PMID:26681847

  5. Combined oral contraceptives: venous thrombosis.

    Science.gov (United States)

    de Bastos, Marcos; Stegeman, Bernardine H; Rosendaal, Frits R; Van Hylckama Vlieg, Astrid; Helmerhorst, Frans M; Stijnen, Theo; Dekkers, Olaf M

    2014-03-03

    Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. We selected studies including healthy women taking COC with VT as outcome. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene

  6. Oral hypoglycaemic agents in 118 diabetic pregnancies

    DEFF Research Database (Denmark)

    Hellmuth, E; Damm, P; Mølsted-Pedersen, L

    2000-01-01

    AIMS: To assess maternal and neonatal complications in pregnancies of diabetic women treated with oral hypoglycaemic agents during pregnancy. METHODS: A cohort study including all consecutively registered, orally treated pregnant diabetic patients set in a diabetic obstetrical service...... at a university hospital: 50 women treated with metformin, 68 women treated with sulphonylurea during pregnancy and a reference group of 42 diabetic women treated with insulin during pregnancy. RESULTS: The prevalence of pre-eclampsia was significantly increased in the group of women treated with metformin...

  7. 21 CFR 872.6030 - Oral cavity abrasive polishing agent.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Oral cavity abrasive polishing agent. 872.6030... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6030 Oral cavity abrasive polishing agent. (a) Identification. An oral cavity abrasive polishing agent is a device in paste or powder form...

  8. Comparative effectiveness of vildagliptin in combination with other oral anti-diabetes agents in usual-care conditions: the EDGE-Latin America study.

    Science.gov (United States)

    Mendivil, Carlos O; Márquez-Rodríguez, Eduardo; Angel, Iván D; Paz, Gustavo; Rodríguez, Cruz; Almada, Jorge; Szyskowsky, Ofelia

    2014-09-01

    To assess the proportion of patients on vildagliptin add-on dual therapy who respond to treatment over a 12 month follow-up, relative to comparator oral anti-diabetes dual therapy, in a usual care setting. Participants were patients with type 2 diabetes (T2DM) aged 18 years and older from 311 centers in Argentina, Colombia, Ecuador, Mexico and Venezuela. Patients were taking monotherapy with an oral anti-diabetes drug (OAD), and were prescribed a new add-on OAD based on the judgment of their personal physician. According to this choice, patients were assigned to one of the two cohorts: vildagliptin or comparator OADs. The primary endpoint was the proportion of patients achieving an A1c drop >0.3% without edema, hypoglycemia, weight gain or discontinuation due to gastrointestinal (GI) events. The secondary endpoint was the proportion of patients with baseline A1c ≥7% who reached the goal of an A1c vildagliptin cohort and 771 in the comparator cohort. The proportion of patients reaching the primary endpoint was higher in the vildagliptin cohort (60.3%) than the comparator cohort (50.7%), OR 1.48 (95% CI: 1.25-1.73). The same was observed for the secondary endpoint (44.8 versus 33.1%) OR 1.64 (95% CI: 1.37-1.98). The incidence of adverse events was low and similar between treatment cohorts. In a usual care setting, patients treated with a vildagliptin combination succeeded in lowering A1c to <7%, without weight gain, hypoglycemia or peripheral edema more often than patients treated with comparator combinations, without increased risk of adverse events. Key limitations are the observational nature of the study and its relatively limited 12 month timeframe.

  9. Oral anticancer agent medication adherence by outpatients.

    Science.gov (United States)

    Kimura, Michio; Usami, Eiseki; Iwai, Mina; Nakao, Toshiya; Yoshimura, Tomoaki; Mori, Hiromi; Sugiyama, Tadashi; Teramachi, Hitomi

    2014-11-01

    In the present study, medication adherence and factors affecting adherence were examined in patients taking oral anticancer agents. In June 2013, 172 outpatients who had been prescribed oral anticancer agents by Ogaki Municipal Hospital (Ogaki, Gifu, Japan) completed a questionnaire survey, with answers rated on a five-point Likert scale. The factors that affect medication adherence were evaluated using a customer satisfaction (CS) analysis. For patients with good and insufficient adherence to medication, the median ages were 66 years (range, 21-85 years) and 73 years (range, 30-90 years), respectively (P=0.0004), while the median dosing time was 131 days (range, 3-3,585 days) and 219 days (24-3,465 days), respectively (P=0.0447). In 36.0% (62 out of 172) of the cases, there was insufficient medication adherence; 64.5% of those cases (40 out of 62) showed good medication compliance (4-5 point rating score). However, these patients did not fully understand the effects or side-effects of the drugs, giving a score of three points or less. The percentage of patients with good medication compliance was 87.2% (150 out of 172). Through the CS analysis, three items, the interest in the drug, the desire to consult about the drug and the condition of the patient, were extracted as items for improvement. Overall, the medication compliance of the patients taking the oral anticancer agents was good, but the medication adherence was insufficient. To improve medication adherence, a better understanding of the effectiveness and necessity of drugs and their side-effects is required. In addition, the interest of patients in their medication should be encouraged and intervention should be tailored to the condition of the patient. These steps should lead to improved medication adherence.

  10. Oral Antidiabetic Agents and Cardiovascular Outcomes

    DEFF Research Database (Denmark)

    Pareek, Manan; Bhatt, Deepak L

    2018-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes; however, a direct protective effect of tight glycemic control remains unproven. In fact, until 2008, when concerns related to rosiglitazone prompted regulatory agencies to mandate assessment...... of cardiovascular safety of new antidiabetic agents, little was known about how these medications affected cardiovascular outcomes. Since then, there has been a considerable increase in the number of cardiovascular trials, which employ a noninferiority design and focus on high-risk populations to establish safety...... in the shortest time possible. In this article, we summarize the 4 major cardiovascular outcome trials of oral antidiabetic agents, completed so far. These include 3 dipeptidyl peptidase-4 inhibitors (saxagliptin, alogliptin, and sitagliptin) and 1 sodium-glucose cotransporter-2 inhibitor (empagliflozin). We...

  11. Evaluation of oral abdominal contrast agent containing ferric ammonium citrate

    International Nuclear Information System (INIS)

    Shiga, Toshiko; Kawamura, Yasutaka; Iwasaki, Toshiko

    1991-01-01

    We evaluated the effectiveness of oral MRI contrast agent containing ferric ammonium citrate. Twenty patients were arbitrarily divided into 2 groups according to the given dose of 100 and 200 mg Fe of oral MRI contrast agent. MRI was performed before and immediately after ingesting 300 ml solution of oral MRI contrast agent using a 1.5 T superconducting system (GE: Signa). Each dose of 100 and 200 mg Fe of oral MRI contrast agent produced sufficient enhancement of gastrointestinal tract, enough to make clear the pancreatic contour and porta hepatis. There was no significant change in blood and urine analysis observed after taking oral MRI contrast agent. The use of ferric ammonium citrate as an oral MRI contrast agent seems to add valuable information in performing upper abdominal MRI imaging. (author)

  12. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial

    DEFF Research Database (Denmark)

    Home, Philip D; Pocock, Stuart J; Beck-Nielsen, Henning

    2009-01-01

    .80-1.63) for myocardial infarction, and 0.72 (0.49-1.06) for stroke. Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group (HR 2.10, 1.35-3.27, risk difference per 1000 person-years 2.6, 1.1-4.1). Upper and distal lower limb fracture rates...... failure and of some fractures, mainly in women. Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs. FUNDING: GlaxoSmithKline plc, UK.......BACKGROUND: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared...

  13. Combination therapies in oral squamous cell carcinomas

    International Nuclear Information System (INIS)

    Krishnamurthi, S.; Shanta, V.

    1982-01-01

    The clinical trials are reported involving combined radiotherapy and chemotherapy in oral squamous cell carcinomas. Bleomycin was the only drug that potentiated radiation response in buccal squamous cell carcinomas. The response of the primary tumors was consistent, predictable and reproducible. The following drugs or chemicals were used: synkavit, methotrexate, metronidazole, bleomycin, pepleomycin, and hyperbaric oxygen. The results and their comparison is given in tables

  14. Gestational Diabetes Mellitus Management with Oral Hypoglycemic Agents

    Science.gov (United States)

    Ryu, Rachel J.; Hays, Karen E.; Hebert, Mary F.

    2014-01-01

    Oral hypoglycemic agents such as glyburide (second generation sulfonylurea) and metformin (biguanide) are attractive alternatives to insulin due to lower cost, ease of administration, and better patient adherence. The majority of evidence from retrospective and prospective studies suggests comparable efficacy and safety of oral hypoglycemic agents such as glyburide and metformin as compared to insulin when used in the treatment of women with gestational diabetes mellitus (GDM). Glyburide and metformin have altered pharmacokinetics during pregnancy and both agents cross the placenta. In this article, we review the efficacy, safety and dosage of oral hypoglycemic agents for the treatment of gestational diabetes mellitus. Additional research is needed to evaluate optimal dosage for glyburide and metformin during pregnancy. Comparative studies evaluating the effects of glyburide and metformin on long-term maternal and fetal outcomes are also needed. PMID:25315294

  15. Clinical pharmacology of novel anticancer agents : Focus on oral formulations

    NARCIS (Netherlands)

    de Weger, V.A.

    2017-01-01

    The taxanes paclitaxel and docetaxel have a low oral bioavailability, as a result of poor water solubility and high first-pass effect. The water-solubility could be improved by the development of solid dispersion formulations for oral use. In this thesis it is shown that the combination of the solid

  16. Hypoglycaemia from misuse of oral hypoglycaemic agent in patients ...

    African Journals Online (AJOL)

    In conclusion, misuse of oral hypoglycaemic agents (OHA) to treat LUTS with subsequent presentation in hypoglycaemic coma should be of concern to the health care provider especially the urologist. It is of no benefit and constitutes drug abuse that should be discouraged. Keywords: drug abuse, hypoglycaemia, lower ...

  17. Synthetic Hydroxyapatite as a Biomimetic Oral Care Agent.

    Science.gov (United States)

    Enax, Joachim; Epple, Matthias

    Human tooth enamel consists mostly of minerals, primarily hydroxyapatite, Ca10(PO4)6(OH)2, and thus synthetic hydroxyapatite can be used as a biomimetic oral care agent. This review describes the synthesis and characterization of hydroxyapatite from a chemist's perspective and provides an overview of its current use in oral care, with a focus on dentin hypersensitivity, caries, biofilm management, erosion, and enamel lesions. Reviews and original research papers published in English and German were included. The efficiency of synthetic hydroxyapatite in occluding open dentin tubules, resulting in a protection for sensitive teeth, has been well documented in a number of clinical studies. The first corresponding studies on caries, biofilm management and erosion have provided evidence for a positive effect of hydroxyapatite either as a main or synergistic agent in oral care products. However, more in situ and in vivo studies are needed due to the complexity of the oral milieu and to further clarify existing results. Due to its biocompatibility and similarity to biologically formed hydroxyapatite in natural tooth enamel, synthetic hydroxyapatite is a promising biomimetic oral care ingredient that may extend the scope of preventive dentistry.

  18. Performance Evaluation of the Combined Agent Fire Fighting System (CAFFS)

    National Research Council Canada - National Science Library

    Kalberer, Jennifer

    2003-01-01

    ... of the location. The Combined Agent Fire Fighting System (CAFFS) employs innovations in nozzle design, lightweight composites and combination agents to design a system with extinguishment capabilities of much larger ARFF vehicles...

  19. Evaluation of potential practical oral contrast agents for pediatric magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bisset, G.S. III; Cincinnati Univ., OH; Children's Hospital Medical Center, Cincinnati, OH

    1989-01-01

    Development of a practical oral contrast agent for magnetic resonance imaging is necessary to improve differentiation of bowel from adjacent structures. In order to find a readily available, inexpensive, non-toxic, palatable solution for use in the pediatric population, several formulas, milk products and a common oral sedative were evaluated in vitro. T1, T2 and signal intensity measurements were performed on a 1.5 T system. Similac with standard iron proved to be a useful high signal intensity agent on multiple pulse sequences. Early in vivo experience in four normal volunteers indicates that this agent provides excellent delineation of the stomach and duodenum from contiguous viscera. Distal small bowel visualization is less predictabel. Further clinical trials should confirm the utility of this solution, which contains a combination of iron salts and paramagnetic metallic ions. (orig.)

  20. Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Lund, Søren S; Wetterslev, Jørn

    2009-01-01

    This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk, and this......This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk......, and this beneficial effect may be conserved with the combination of metformin and insulin treatment. However, the effect of glitazones on CVD is uncertain. There is conflicting evidence from large randomized trials to support a protective effect against CVD of lowering blood glucose per se but a systematic review...

  1. Combining Rational and Biological Factors in Virtual Agent Decision Making

    NARCIS (Netherlands)

    Bosse, T.; Gerritsen, C.; Treur, J.

    2011-01-01

    To enhance believability of virtual agents, this paper presents an agent-based modelling approach for decision making, which integrates rational reasoning based on means-end analysis with personal psychological and biological aspects. The agent model developed is a combination of a BDI-model and a

  2. Quantal health effects of three toxic agents combined

    International Nuclear Information System (INIS)

    Seiler, F.A.

    1988-01-01

    Quantal health effects such as cancer, correlated with the combined action of three toxic agents, are considered. Data on the combined effects of two agents are scarce and no such data exist for three toxicants, yet concerns have arisen about simultaneous exposure of radiation workers to three different agents. Using models developed from the analysis of health effects involving two toxicants, equations for the combined effects of three agents are derived from a more general formalism. An application of practical interest is the incidence of cancer of the esophagus and its correlation with concurrent exposures to alcohol, tobacco, and either low- or high-LET radiation. (author)

  3. Fundamental studies of oral contrast agents for MR. Comparison of manganese agent and iron agent

    International Nuclear Information System (INIS)

    Fujita, Osamu; Hiraishi, Kumiko; Suginobu, Yoshito; Takeuchi, Masayasu; Narabayashi, Isamu

    1996-01-01

    We investigated and compared signal intensity and the effect of imaging the upper abdomen with blueberry juice (B.J.), a Mn agent utilizing the properties of paramagnetic metals, and FerriSeltz (F.S.), an iron agent. Since the relaxation effect was much stronger with B.J. than with F.S., the signal intensity required of a peroral contrast agent was able to be obtained at a much lower concentration of B.J. In imaging the upper abdomen, B.J. had a positive effect on imaging in T1-weighted images, and a negative effect in T2-weighted images. F.S. had a positive imaging effect in both, and because it showed extremely high signals in T2-weighted images, motion artifact arose. (author)

  4. Inventory of oral anticancer agents : Pharmaceutical formulation aspects with focus on the solid dispersion technique

    NARCIS (Netherlands)

    Sawicki, E.; Schellens, J. H M; Beijnen, J. H.; Nuijen, B.

    2016-01-01

    Dissolution from the pharmaceutical formulation is a prerequisite for complete and consistent absorption of any orally administered drug, including anticancer agents (oncolytics). Poor dissolution of an oncolytic can result in low oral bioavailability, high variability in blood concentrations and

  5. Efficacy and safety comparison of add-on therapy with liraglutide, saxagliptin and vildagliptin, all in combination with current conventional oral hypoglycemic agents therapy in poorly controlled Chinese type 2 diabetes.

    Science.gov (United States)

    Li, C-J; Yu, Q; Yu, P; Zhang, Q-M; Ding, M; Liu, X-J; Yu, D-M

    2014-09-01

    control with conventional oral hypoglycemic agents. These findings support the add-on of liraglutide could offer notable advantages over DPP-4 inhibitors in both efficacy and safety. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  6. Ficus Deltoidea: A potential source for new oral antidiabetic agent

    International Nuclear Information System (INIS)

    Zainah Adam; Juliana Mahamad Napiah; Shafii Khamis; Muhajir Hamid

    2012-01-01

    Ficus deltoidea or locally known as Mas Cotek is one of the common medicinal plant used in Malaysia. Ethno botanical approaches showed that this plant possess antidiabetic property. Previous study had shown that F. deltoidea reduced hyperglycemia in type I diabetic rats at different prandial state. This study was done to elucidate the possible antihyperglycemic mechanisms of F. deltoidea. The results showed that F. deltoidea significantly stimulated insulin secretion from pancreatic β-cells with the highest magnitude of stimulation was 7.31-fold (p 50 value was 4.15±0.25 mg/ml. Kinetic analysis of the enzyme activity revealed the F. deltoidea exhibited a mixed-type inhibition mechanism against sucrase activity. Such observations showed that F. deltoidea has the potential to be developed as new oral antidiabetic agent for the treatment of diabetes mellitus. (author)

  7. Oral available agents in the treatment of RRMS

    Directory of Open Access Journals (Sweden)

    Aupérin T

    2013-10-01

    Full Text Available Thierry Aupérin Medical Communications, Global MS Medical Affairs, Genzyme Corporation, Cambridge, MA, USAWe read with interest the article by Drs Thöne and Ellrichmann entitled "Oral available agents in the treatment of relapsing remitting multiple sclerosis: an overview of merits and culprits" recently published in Drug, Healthcare and Patient Safety.1 The review provides a valuable overview of a number of new therapeutic options for multiple sclerosis (MS, with a focus on proposed mechanisms of action and efficacy and safety profiles of the respective agents.In reading the article, however, we did note a number of errors pertaining to teriflunomide, a once-daily oral immunomodulator approved in several countries for the treatment of relapsing forms of MS (RMS and relapsing-remitting MS (RRMS. The most significant error pertains to a statement made within the safety section, which states: "Serious adverse effects (AEs included pathological liver function, neutropenia, and trigeminal neuralgia as well as one case of progressive multifocal leukoencephalopathy (PML in a patient with systemic lupus erythematosus." We would like to draw the authors’ attention to the fact that this case of PML pertains to the use of the related drug, leflunomide, and not teriflunomide as suggested. It is important to note that leflunomide is licensed to treat active rheumatoid arthritis in adults, and has not been evaluated or approved for the treatment of MS; as such it is inappropriate to extrapolate this observation to the use of teriflunomide. Furthermore, the case of PML cited in the article is complicated by the fact that the patient received prior multiple immunosuppressant therapies before leflunomide (ie, prednisone, azathioprine, chloroquine, danazol, cyclosporin A and methotrexate, which may have contributed to the development of PML.View original paper by Thöne and Ellrichmann.

  8. Efficacy of Some Combination Regimens of Oral Hypoglycaemic ...

    African Journals Online (AJOL)

    Purpose: To examine the efficacy of selected oral hypoglycaemic agent (OHA) regimens in a small group of patients receiving such treatment. Methods: This was a retrospective, observational study that involved patients who had been diagnosed with type 2 diabetes mellitus and undergoing routine follow-up at a teaching ...

  9. In vitro susceptibilities of zygomycetes to combinations of antimicrobial agents.

    NARCIS (Netherlands)

    Danaoui, E.; Afeltra, J.; Meis, J.F.G.M.; Verweij, P.E.

    2002-01-01

    Combinations of antimicrobial agents were tested against 35 strains of zygomycetes. The interaction between amphotericin B and rifampin was synergistic or additive. Flucytosine alone was inactive and, upon combination with amphotericin B, synergy was not achieved. The combination of amphotericin B

  10. Oral agents for ovulation induction:Old drugs revisited and new drugs re-evaluated

    NARCIS (Netherlands)

    Badawy, A.M.M.

    2008-01-01

    The aim of this thesis was to address a number of questions regarding oral agents used for ovulation induction. We were motivated to run the presented trials because of many reasons. Firstly, although oral agents, namely CC, have been in the market for decades, many basic aspects regarding the

  11. Quantal health effects for a combination of several toxic agents

    Energy Technology Data Exchange (ETDEWEB)

    Seiler, F A

    1988-12-01

    Quantal health effects caused by the combined action of a number of toxic agents are modeled using the information available for each toxicant acting in isolation. Two basic models are used; one assumes no interaction, the other postulates a separable kind of interaction in which each agent contributes an enhancement factor independent of all other agents. These two models provide yardsticks by which to measure synergisms and antagonisms in the interaction between the effects of toxic agents. Equations are given in approximations for small and large values of the risk. (author)

  12. Quantal health effects for a combination of several toxic agents

    International Nuclear Information System (INIS)

    Seiler, F.A.

    1988-01-01

    Quantal health effects caused by the combined action of a number of toxic agents are modeled using the information available for each toxicant acting in isolation. Two basic models are used; one assumes no interaction, the other postulates a separable kind of interaction in which each agent contributes an enhancement factor independent of all other agents. These two models provide yardsticks by which to measure synergisms and antagonisms in the interaction between the effects of toxic agents. Equations are given in approximations for small and large values of the risk. (author)

  13. 10% low density corn-oil emulsion oral contrast agent for abdominal computed tomography

    International Nuclear Information System (INIS)

    Choi, Sun Kyou; Chon, Dong Kwon; Han, Young Min; Kim, Chong Soo; Sohn, Myung Hee; Song, Ho Young; Choi, Ki Chul

    1990-01-01

    CT of the gastrointestinal tract is commonly performed after administration of a high-density diluted iodinated oral contrast material. However, because if inadequate mixing of the contrast material with the gastrointestinal contents, pseudotumor and poor mucosal visualization are frequently shown on abdominal CT. To overcome these problem, 10% corn oil emulsion (COE) is tested as an alternative oral contrast agent in 40 patients. We analyse patients tolerance, gastric mucosal visualization and discrimination of pancreas from the duodenal C-loop to 10% COE in 40 patients compared with those obtained from 35 patients, who was received high-density diluted iodinated oral contrast agent (gastrografin). The results are as follows : 1. Patients' tolerance to 10% COE is similar to that to conventional oral contrast agent. 2. Image of the gastric mucosa from patients receiving 10% COE is superior to that receiving oral contrast agent. 3. The discrimination between pancreatic head from duodenal C-loop is better in patients receiving 10% COE than in patients receiving conventional oral contrast agent. 4. In patients receiving 10% COE, differentiation of cystic masses from intestinal loops is sometimes difficult. The results of this study indicate that 10% COE may be useful oral contrast agent for optimal visualization of gastric mucosa and pancreatico-duodenal discrimination on abdominal CT

  14. Oral combination chemotherapy in the treatment of AIDS ...

    African Journals Online (AJOL)

    Objectives: To determine the effectiveness of an oral combination chemotherapy regimen administered to patients with AIDS-associated Hodgkin's disease. Design: Prospective, pilot phase II clinical trial. Setting: Consecutive patient recruitment occurred at two medical centers in the United States: Albany Medical Center, ...

  15. Contraception with combined oral contraceptive pills in Port ...

    African Journals Online (AJOL)

    Mass media was the commonest source of information, and one accidental pregnancy occurred (Pearl index 0.03 per 100 woman years). Conclusion: This study shows that combined oral contraceptives pills appear to be acceptable, safe and effective in Port Harcourt. This compares to world wide experience. Concerted ...

  16. Influence of combined oral contraceptives on the periodontal condition

    Directory of Open Access Journals (Sweden)

    Roberta Santos Domingues

    2012-04-01

    Full Text Available Most studies investigating the impact of oral contraceptives have been performed some years ago, when the level of sexual hormones was greater than the actual formulations. Objective: The aim of this study was to evaluate the effects of current combined oral contraceptives (COC on periodontal tissues, correlating the clinical parameters examined with the total duration of continuous oral contraceptive intake. Material and methods: Twenty-five women (19-35 years old taking combined oral contraceptives for at least 1 year were included in the test group. The control group was composed by 25 patients at the same age range reporting no use of hormone-based contraceptive methods. Clinical parameters investigated included pocket probing depth (PD, clinical attachment level (CAL, sulcular bleeding index (SBI and plaque index (Pl.I. Data were statistically evaluated by unpaired t test, Pearson’s correlation test and Spearman’s correlation test. Results: The test group showed increased PD (2.228±0.011 x 2.154±0.012; p<0.0001 and SBI (0.229±0.006 x 0.148±0.005, p<0.0001 than controls. No significant differences between groups were found in CAL (0.435±0.01 x 0.412±0.01; p=0.11. The control group showed greater Pl.I than the test group (0.206±0.007 x 0.303±0.008; p<0.0001. No correlation between the duration of oral contraceptive intake, age and periodontal parameters was observed. Conclusions: These findings suggest that the use of currently available combined oral contraceptives can influence the periodontal conditions of the patients, independently of the level of plaque accumulation or total duration of medication intake, resulting in increased gingival inflammation.

  17. Antimicrobial efficacy of oral topical agents on microorganisms associated with radiated head and neck cancer patients: an in vitro study.

    Science.gov (United States)

    Bidra, Avinash S; Tarrand, Jeffery J; Roberts, Dianna B; Rolston, Kenneth V; Chambers, Mark S

    2011-04-01

    A variety of oral topical agents have been used for prevention and management of radiotherapy-induced adverse effects. The antimicrobial nature of some of the commonly used agents is unknown. The purpose of this study was to evaluate antimicrobial efficacies of various oral topical agents on common microorganisms associated with radiated head and neck cancer patients. Seven commonly used topical oral agents-0.12% chlorhexidine with alcohol, 0.12% chlorhexidine without alcohol, baking soda-salt rinse, 0.4% stannous fluoride gel, 0.63% stannous fluoride rinse, calcium phosphate mouthrinse, and acemannan hydrogel (aloe vera) rinse-were evaluated in vitro for their antimicrobial efficacies against four common microorganisms. A combination of baking soda-salt rinse and 0.4% stannous fluoride gel was evaluated as the eighth agent. The microorganisms used were Staphylococcus aureus, group B Streptococcus, Escherichia coli, and Candida albicans. An ELISA reader was used to measure the turbidity of microbial culture wells and optical density (OD) values for each of the 960 wells recorded. Mean OD values were rank ordered based on their turbidity. One-way ANOVA with Tukey HSD post hoc analysis was used to study differences in OD values (P baking soda- salt, calcium phosphate rinse, and the combination of baking soda-salt and stannous fluoride gel. Mean OD values classified for microorganisms from lowest to highest were Escherichia coli, Staphylococcus aureus, group B Streptococcus, and Candida albicans. A significant difference among the antimicrobial efficacies of topical agents was evident for each of four microorganisms (P < .05). There was also a significant difference among the antimicrobial efficacies of the same topical agent on the four microorganisms tested (P < .05).

  18. Biocompatibility of Portland cement combined with different radiopacifying agents.

    Science.gov (United States)

    Lourenço Neto, Natalino; Marques, Nádia C T; Fernandes, Ana Paula; Rodini, Camila O; Duarte, Marco A H; Lima, Marta C; Machado, Maria A A M; Abdo, Ruy C C; Oliveira, Thais M

    2014-03-01

    The aim of this study was to evaluate the response of rat subcutaneous tissue to Portland cement combined with two different radiopacifying agents, iodoform (CHI3) and zirconium oxide (ZrO2). These materials were placed in polyethylene tubes and implanted into the dorsal connective tissue of Wistar rats for 7 and 15 days. The specimens were then stained with hematoxylin and eosin, and inflammatory reaction parameters were evaluated by light microscopy. The intensity of the inflammatory response to the sealants was analyzed by two blind calibrated observers throughout the experimental period. Histological analysis showed that all the materials caused a moderated inflammatory reaction at 7 days, which then diminished with time. At 15 days, the inflammatory reaction was almost absent, and fibroblasts and collagen fibers were observed indicating normal tissue healing. The degrees of the inflammatory reaction on different days throughout the experimental period were compared using the non-parametric Kruskal-Wallis test. Statistical analysis demonstrated no significant differences amongst the groups, and Portland cement associated with radiopacifying agents gave satisfactory results. Therefore, Portland cement used in combination with radiopacifying agents can be considered a biocompatible material. Although our results are very encouraging, further studies are needed in order to establish safe clinical indications for Portland cement combined with radiopacifying agents.

  19. Combinations of genetic data in a study of oral cancer

    DEFF Research Database (Denmark)

    Mellerup, Erling Thyge; Møller, Gert Lykke; Mondal, Pinaki

    2015-01-01

    In the single locus strategy a number of genetic variants are analyzed, in order to find variants that are distributed significantly different between controls and patients. A supplementary strategy is to analyze combinations of genetic variants. A combination that is the genetic basis...... for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented...

  20. Safe practices and financial considerations in using oral chemotherapeutic agents.

    Science.gov (United States)

    Bartel, Sylvia B

    2007-05-01

    Safe handling practices and financial concerns associated with oral chemotherapy in non-traditional settings are discussed. Oral chemotherapy may pose a risk to patients because of a narrow therapeutic index, complex dosing regimen, dispensing by community pharmacists without prescription order review by an oncology pharmacist or nurse, or self-administration in the home or another nontraditional setting, where patient monitoring is infrequent. Errors in prescribing, dispensing, and administration and patient or caregiver misunderstandings are potential problems with the use of oral chemotherapy that need to be addressed when developing safe practices. Changes in Medicare pharmaceutical reimbursement rates and rules need to be monitored because they have the potential to affect patient care and outcomes. Patient assistance programs and advocacy groups can help alleviate financial concerns associated with oral chemotherapy. Consensus guidelines specific to safe handling of oral chemotherapy in the home or other nontraditional setting need to be developed. Also, healthcare providers must understand reimbursement and provide direction to patients when patient assistance programs or advocacy groups can assist with the financial challenges of oral chemotherapy.

  1. The primary applications of Gd-DTPA as an oral negative gastrointestinal contrast agent for MRCP

    International Nuclear Information System (INIS)

    Chen Yanping; Zhang Xuelin; Cheng Guanxun; Chang Renmin; Zhang Yuzhong; Cang Peng; Xia Qiong

    2003-01-01

    Objective: Using oral Gd-DTPA as a negative contrast agent to null the bowel signal during MR cholangiopancreatography (MRCP) to improve the quality of MRCP. Methods: A phantom study was performed to select the optimal concentration of Gd-DTPA to be used as an oral negative contrast agent in MRCP. 15 patients suspected of biliary tract and pancreatic disease were performed with MRCP before and after using 250 ml oral contrast agents (1:5 diluted Gd-DTPA, 1.488 g/L). All MR images were acquired using a 1.5 T whole body MR scanner (Vision Plus, Siemens). MRCP was acquired using two-dimensional single slice fast spin-echo sequence and HASTE (half-fourier acquisition single-shot fast spin echo) sequence. Results: The phantom study showed that the dilution ratio 1:5 of Gd-DTPA oral contrast agent was best in decreasing the signal intensity both in T 2 WI (59.3%) and in HASTE sequence (82.45%). All the dilution ratio of Gd-DTPA oral contrast agent decreased the signal intensity up to 90% on single slice MRCP. In all the patients the high signal intensity from the stomach and intestinal fluid was completely suppressed. The depictions of common bile duct and pancreatic duct were markedly improved by the oral contrast agent (P<0.05). Conclusion: 1:5 diluted (1.488 g/L) oral MR contrast agent Gd-DTPA can be an effective and safe negative contrast agent in eliminating signal intensity of the gastrointestinal tract, thus improving the depiction of the biliary system in MRCP

  2. Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

    International Nuclear Information System (INIS)

    Yamashita, Yoshio; Goto, Masaaki; Katsuki, Takeshi

    2002-01-01

    Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

  3. Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Yoshio; Goto, Masaaki; Katsuki, Takeshi [Saga Medical School (Japan)

    2002-06-01

    Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

  4. Combining Targeted Agents With Modern Radiotherapy in Soft Tissue Sarcomas

    Science.gov (United States)

    Wong, Philip; Houghton, Peter; Kirsch, David G.; Finkelstein, Steven E.; Monjazeb, Arta M.; Xu-Welliver, Meng; Dicker, Adam P.; Ahmed, Mansoor; Vikram, Bhadrasain; Teicher, Beverly A.; Coleman, C. Norman; Machtay, Mitchell; Curran, Walter J.

    2014-01-01

    Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes. PMID:25326640

  5. New oral anticoagulant and antiplatelet agents for neurosurgeons.

    Science.gov (United States)

    Kimpton, George; Dabbous, Bassam; Leach, Paul

    2015-01-01

    Until recently, warfarin, clopidogrel and aspirin have provided the mainstay for prevention of thrombotic disease in cardiac patients. However, new classes of drugs have recently emerged that promise better clinical outcomes and lower risks. Use of such agents has increased, but increased risk and severity of intra-cranial haemorrhage (ICH) still remain. These cases of intra-cranial bleeds present as emergencies to neurosurgical units. It is of paramount importance that neurosurgical practitioners are aware of those new drugs, useful monitoring tests and available emergency reversal options in case the patient needs emergency intervention. In this review we survey newly available agents in the U.K. at the time of publication. We look at the data provided by the manufacturers, related publications and international guidelines for their use and reversal. New anticoagulants offer a lower incidence of ICH compared with warfarin. Advanced and accurate monitoring tests are emerging, as are prospective data on reversal of anticoagulation in bleeding. Some standard coagulation tests may be of use, whilst reversal agents are available and being evaluated. The trial data shows that new antiplatelet agents have similar or increased incidence and severity of intra-cranial ICH compared with clopidogrel. There is currently limited data on monitoring or reversal. We suggest they may be managed similarly to clopidogrel by using platelet reactivity assays, optimising platelet count and using platelet transfusion with adjunctive agents.

  6. Protective single/combined treatment with betel leaf and turmeric against methyl (acetoxymethyl) nitrosamine-induced hamster oral carcinogenesis.

    Science.gov (United States)

    Azuine, M A; Bhide, S V

    1992-05-28

    The inhibitory effect of oral administration of betel-leaf extract (BLE) and 2 of its constituents, beta-carotene and alpha-tocopherol, as single agents or in combination with dietary turmeric on methyl(acetoxymethyl)nitrosamine (DMN-OAC)-induced oral carcinogenesis in Syrian hamsters was studied. DMN-OAC was administered twice monthly for 6 months. The chemopreventive effect of BLE or its constituents with turmeric was determined by comparing tumor incidence observed in treated groups with that seen in control animals. The apparent site-specific chemopreventive effect of BLE or its constituents was demonstrated by inhibition of tumor incidence, reduction of tumor burden, extension of the tumor latency period and regression of established, frank tumors. The inhibitory effect of BLE or its constituents combined with turmeric was higher than that of the individual constituents. The study suggests that BLE could be developed as a potential chemopreventive agent for human oral cancer.

  7. Systematic review of natural agents for the management of oral mucositis in cancer patients

    DEFF Research Database (Denmark)

    Yarom, Noam; Ariyawardana, Anura; Hovan, Allan

    2013-01-01

    /or conflicting evidence. CONCLUSIONS: Of the various natural agents reviewed here, the available evidence supported a guideline only for two agents: a suggestion in favor of zinc and a recommendation against glutamine, in the treatment settings listed above. Well-designed studies of other natural agents......Abstract PURPOSE: The aim of this study was to review the available literature and define clinical practice guidelines for the use of natural agents for the prevention and treatment of oral mucositis. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational...

  8. Congenital malformations in offspring of diabetic women treated with oral hypoglycaemic agents during embryogenesis

    DEFF Research Database (Denmark)

    Hellmuth, E; Damm, P; Mølsted-Pedersen, L

    1994-01-01

    A markedly increased risk (50%) of congenital malformations in the offspring of women treated with oral hypoglycaemic agents during the first trimester has recently been reported. With this background, the medical records of a consecutive sample of 25 pregnant Type 2 diabetic women treated...... with oral hypoglycaemic agents during embryogenesis between 1966 and 1991 in the diabetic service of a university hospital, were studied retrospectively. None of the infants had major congenital malformations disclosed in the neonatal period (0%, 97.5% confidence interval 0.0-13.7%), but one minor...... congenital malformation was found (4.0%, 95% confidence interval 0.1-20.3%). Although this study, due to the limited number of pregnancies examined, does not exclude an association between treatment with oral hypoglycaemic agents at the time of embryogenesis and major congenital malformations...

  9. Comparison of oral ketamine and oral midazolam as sedative agents in pediatric dentistry

    Directory of Open Access Journals (Sweden)

    Damle S

    2008-09-01

    Full Text Available The safe and effective treatment of uncooperative or combative preschool children with extensive dental needs is one of pediatric dentist′s ongoing challenges. The traditional methods of behavior management are no longer acceptable to parents as they are not ready to spare more time for dental treatment of their children. Keeping this in mind, the present study was designed and carried out to evaluate the sedative effects of oral ketamine and oral midazolam prior to general anesthesia. Twenty uncooperative children in the age-group of 2-6 years were selected after thorough medical examination and investigations. Informed consent was obtained from the parent. This was a randomized double-blind study. An anesthesiologist administered either 0.5 mg/kg midazolam or 5 mg/kg ketamine orally. The heart rate, respiratory rate, and oxygen saturation were recorded at regular intervals. The sedation and anxiolysis scores were also recorded. The parents were asked to answer a questionnaire at the follow-up session the next day on the surgical experience of the parent and the child and side effects experienced, if any. When the data was subjected to statistical analysis, it was observed that both drugs resulted in adequate sedation at the end of 30 min, with oral midazolam providing significantly better anxiolysis. The heart rate and respiratory rate were marginally higher with oral ketamine. The questionnaire revealed a better response with oral midazolam; side effects were more prominent with oral ketamine.

  10. Assessing the Risk of Birth Defects Associated with Exposure to Fixed-Dose Combined Antituberculous Agents during Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    O. Awodele

    2012-01-01

    Full Text Available Due to the risks of disease progression and transmission to the newborn, treatment of tuberculosis is often pursued during pregnancy and fixed-dose combined antituberculous agents have been found to be beneficial. Unfortunately, there is paucity of data on the safety of the fixed-dose combined antituberculous drugs during pregnancy. This study intends to assess the teratogenic effect of fixed-dose combined antituberculous drugs on the organogenesis stage of fetal development and also investigate the possible roles of vitamin C in modulating the teratogenic effects of these agents on the fetus using animal model. Pregnant rats were divided into 3 groups with 12 animals per group: group 1 received distilled water (10 mL/kg orally; group 2 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents plus vitamin C (10 mg/kg/day orally. Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation, and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and hematological examination. The liver, kidney, heart, and brain of all the sacrificed animals were used for histopathological examination. There were significant (≤0.05 low birth weights of the foetuses of the animals that were treated with fixed-dose combined antituberculous agents. The haematological parameters also revealed a reduction in the platelets counts and neutrophiles at the first filial generation. Significant (≤0.05 elevations in the levels of aspartate aminotransferase (AST and alkaline phosphatase (ALP in the foetuses of the animals treated with fixed-dose combined antituberculous agents were also observed. However, the combination of vitamin C with fixed-dose combined antituberculous agents

  11. Sacubitril/Valsartan: A Novel Cardiovascular Combination Agent.

    Science.gov (United States)

    Sible, Alexandra M; Nawarskas, James J; Alajajian, David; Anderson, Joe R

    2016-01-01

    Sacubitril/valsartan [LCZ696 (Entresto), Novartis Pharmaceuticals Corp.] is the first in a new class of drugs that combines neprilysin inhibition with angiotensin II receptor antagonism, the combination of which acts to increase endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system. Sacubitril/valsartan has been studied in the treatment of hypertension, heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF) and has demonstrated clinical efficacy in blood pressure reduction in hypertensive patients with and without HFpEF and a reduction in hospitalizations and mortality for patients with HFrEF. Research to evaluate clinical outcomes in HFpEF is ongoing. Sacubitril/valsartan is approved to reduce hospitalization and risk of cardiovascular death for patients with HFrEF in New York Heart Association (NYHA) functional class II-IV. The product is as well tolerated as an angiotensin-converting enzyme inhibitor, with the most common side effect being hypotension. Expectedly, it is much more costly than generic angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, which will be a factor in determining how widespread the use of this agent will be. In summary, although the number of published studies evaluating its use is limited, sacubitril/valsartan represents a promising new treatment option for patients with HFrEF. Ongoing studies will continue to refine the role of this agent in clinical practice.

  12. Oral (Systemic) Botanical Agents for the Treatment of Psoriasis: A Review.

    Science.gov (United States)

    Farahnik, Benjamin; Sharma, Divya; Alban, Joseph; Sivamani, Raja

    2017-06-01

    Patients with psoriasis often use botanical therapies as part of their treatment. It is important for clinicians to be aware of the current evidence regarding these agents as they treat patients. A systematic literature search was conducted using the PubMed, MEDLINE, and EMBASE database for randomized clinical trials assessing the use of botanical therapeutics for psoriasis. The search included the following keywords: "psoriasis" and "plant" or "herbal" or "botanical." Citations within articles were also reviewed to identify relevant sources. The results were then further refined by route of administration, and the oral (systemic) botanical agents are reviewed herein. A total of 12 controlled and uncontrolled clinical trials addressing the use of oral, systemic botanical agents for psoriasis were assessed in this review. While overall evidence is limited in quantity and quality, HESA-A, curcumin, neem extract, and, to a lesser degree, Traditional Chinese Medicine seem to be the most efficacious agents. The literature addresses a large amount of studies in regards to botanicals for the treatment of psoriasis. While most agents appear to be safe, further research is necessary for evidence-based recommendation of oral botanical agents to psoriasis patients.

  13. Oral Hypoglycemic Agents Added to Insulin Monotherapy for Type 2 Diabetes

    NARCIS (Netherlands)

    Vos, Rimke C.; Rutten, Guy E.H.M.

    2017-01-01

    Clinical Question: Among patients with type 2 diabetes mellitus who do not achieve optimal glycemic control with insulin monotherapy, is the addition of oral hypoglycemic agents associated with benefits (measured by lowering of hemoglobin A1c) or adverse effects? Bottom Line: Adding a sulfonylurea

  14. Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants.

    Science.gov (United States)

    Ansell, Jack E

    2016-02-01

    Although there is controversy about the absolute need for a reversal agent for the new direct oral anticoagulants (DOACs), the absence of such an agent is a barrier to more widespread use of these agents. For the management of major life-threatening bleeding with the DOACs, most authorities recommend the use of four factor prothrombin complex concentrates, although the evidence to support their use in terms of improving outcomes is meager. At the present time, there are three antidotes in development and poised to enter the market. Idarucizumab is a drug-specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran. Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Ciraparantag is a universal antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.

  15. Effects of oral contraceptive agents and sex steroids on carbohydrate metabolism.

    Science.gov (United States)

    Kalkhoff, R K

    1972-01-01

    The article offers a general interpretation of the influence of oral contraceptive agents on glucose tolerance, emphasizing comparisons of synthetic sex hormones. Although there are conflicting reports on steroid-induced diabetes in normal women, their glucose curves are often higher when under oral contraceptive treatment, suggesting that oral contraceptives may induce a form of subclinical diabetes melitus that is reversible. Evidence from diabetic women suggests definite deliterious effects from contraceptive administration. Estradiol, estriol, and estrone may improve glucose tolerance in nondiabetic women and reduce insulin requirements in diabetics. Progesterone has little effect on carbohydrate tolerance, as did synthetic progestin. Conjugated equine estrogens (equilenine or Premarin) may provoke mild to moderate deterioration of carbohydrate tolerance. Parenterally administered natural estrogens and orally administered synthetic derivatives appear to differ sharply in their effects. Sex hormones' effects on carbohydrate metabolism likely involve interactions with insulin and endogenous glucocorticoids.

  16. Using tools and technology to promote education and adherence to oral agents for cancer.

    Science.gov (United States)

    Burhenn, Peggy S; Smudde, Josephine

    2015-06-01

    The use of oral agents for cancer (OACs) is increasing, and oncology nurses are in an ideal position to educate patients about them and suggest methods to improve adherence. Once an OAC is ordered, the administration is the responsibility of the patient. Oncology nurses can use tools and technology to assist with education, which may promote adherence, and suggest reminder tools that can be used. Many electronic tools have been developed, such as smartphone applications, text messaging, electronic alarms, and glowing pill bottles. The researchers reviewed electronic devices, as well as traditional methods such as calendars and pillboxes, that can assist patients in remembering to take the medication they are administering at home. A literature search was compiled and websites were searched for patient education tools, reminder tools (electronic and manual), and smartphone applications. The project was part of the Oncology Nursing Society Putting Evidence Into Practice effort on oral adherence. Education alone is insufficient to promote adherence to oral medication regimens. Multicomponent interventions have demonstrated improved adherence, and tools and technology directed at improving adherence to oral agents can be used. The researchers found multiple reminder aids to assist patients in adhering to an oral regimen. They are highlighted in this article.

  17. Combined Use of Self-Efficacy Scale for Oral Health Behaviour and Oral Health Questionnaire: A Pilot Study

    Science.gov (United States)

    Soutome, Sakiko; Kajiwara, Kazumi; Oho, Takahiko

    2012-01-01

    Objective: To examine whether the combined use of a task-specific self-efficacy scale for oral health behaviour (SEOH) and an oral health questionnaire (OHQ) would be useful for evaluating subjects' behaviours and cognitions. Design: Questionnaires. Methods: One hundred and eighty-five students completed the SEOH and OHQ. The 30-item OHQ uses a…

  18. Combined preoperative therapy for oral cancer with nedaplatin and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Masatoshi; Shibata, Akihiko; Hayashi, Munehiro [Nippon Dental Univ., Tokyo (Japan). Hospital] (and others)

    2002-03-01

    We performed preoperative combined therapy using nedaplatin (CDGP) and radiation in 12 patients with squamous cell carcinoma originating from the oral cavity and maxillary sinus, and examined for any adverse events that may have occurred during this therapeutic regimen. Regarding the irradiation, external irradiation utilizing a 6 MV linac (linear accelerator) at a dose of 2.0 Gy/day was performed 5 times a week, with the target total radiation dose set at 40 Gy. In addition, CDGP was intravenously administered 30 minutes before irradiation at a dose of 5 mg/m{sup 2}/day. Mucositis was observed in all 12 subjects, however, the severity was observed to be grade 1-2 with no major differences in comparison to the patients given standard radiation monotherapy. Two subjects developed grade 3 leucopenia and were thus given granulocyte colony stimulating factor (G-CSF). In addition, grade 2 and grade 3 thrombocytopenia were both observed in one subject each. The subject with grade 3 thrombocytopenia required a platelet transfusion during surgery. No marked changes in serum creatinine levels were noted. These findings are therefore considered to provide evidence supporting the safety of this combination therapy. (author)

  19. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

    Science.gov (United States)

    Liu, JunLi; Wang, YiHu; Song, ShuJun; Wang, XiJie; Qin, YaYa; Si, ShaoYan; Guo, YanChuan

    2015-01-01

    Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

  20. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

    Directory of Open Access Journals (Sweden)

    JunLi Liu

    Full Text Available Collagen peptides (CPs and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8 for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg; OVX + calcium citrate (75 mg/kg. After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

  1. Combination of vascular targeting agents with thermal or radiation therapy

    International Nuclear Information System (INIS)

    Horsman, Michael R.; Murata, Rumi

    2002-01-01

    Purpose: The most likely clinical application of vascular targeting agents (VTAs) is in combination with more conventional therapies. In this study, we report on preclinical studies in which VTAs were combined with hyperthermia and/or radiation. Methods and Materials: A C3H mammary carcinoma grown in the right rear foot of female CDF1 mice was treated when at 200 mm 3 in size. The VTAs were combretastatin A-4 disodium phosphate (CA4DP, 25 mg/kg), flavone acetic acid (FAA, 150 mg/kg), and 5,6-dimethylxanthenone-4-acetic acid (DMXAA, 20 mg/kg), and were all injected i.p. Hyperthermia and radiation were locally administered to tumors of restrained, nonanesthetized mice, and response was assessed using either a tumor growth or tumor control assay. Results: Heating tumors at 41.5 degree sign C gave rise to a linear relationship between the heating time and tumor growth with a slope of 0.02. This slope was increased to 0.06, 0.09, and 0.08, respectively, by injecting the VTAs either 30 min (CA4DP), 3 h (FAA), or 6 h (DMXAA) before heating. The radiation dose (±95% confidence interval) that controls 50% of treated tumors (the TCD 50 value) was estimated to be 53 Gy (51-55 Gy) for radiation alone. This was decreased to 48 Gy (46-51 Gy), 45 Gy (41-49 Gy), and 42 Gy (39-45 Gy), respectively, by injecting CA4DP, DMXAA, or FAA 30-60 min after irradiating. These values were further decreased to around 28-33 Gy if the tumors of VTA-treated mice were also heated to 41.5 degree sign C for 1 h, starting 4 h after irradiation, and this effect was much larger than the enhancement seen with either 41.5 degree sign C or even 43 degree sign C alone. Conclusions: Our preclinical studies and those of others clearly demonstrate that VTAs can enhance tumor response to hyperthermia and/or radiation and support the concept that such combination studies should be undertaken clinically for the full potential of VTAs to be realized

  2. Computed tomography enterography: a comparison of different neutral oral contrast agents

    International Nuclear Information System (INIS)

    D'Ippolito, Giuseppe; Braga, Fernanda Angeli; Resende, Marcelo Cardoso; Bretas, Elisa Almeida Sathler; Nunes, Thiago Franchi; Rosas, George de Queiroz; Tiferes, Dario Arie

    2012-01-01

    Objective: The purpose of this study was to assess the performance of neutral oral contrast agents, comparing intestinal distension, distinction of intestinal wall, acceptance and side effects. Materials and Methods: Prospective, randomized, and double-blinded study involving 30 patients who underwent computed tomography of abdomen and pelvis with administration of neutral oral contrast agents, divided into three groups according the contrast agent type: milk, water, and polyethylene glycol. The images were consensually analyzed by two observers, considering the degree of bowel distension and intestinal wall distinction. The patients responded to a questionnaire regarding the taste of the ingested solution and on their side effects. Kruskal-Wallis and chi-square tests were employed for statistical analysis. Results: Among 40 studied intestinal segments, appropriate bowel distension (intestinal loop diameter > 2 cm) was observed in 14 segments (35%) in the milk group, 10 segments (25%) in the water group and 23 segments (57%) in the polyethylene glycol group (p = 0.01). Preparation with polyethylene glycol resulted in the best bowel distension, but it presented the worst taste and highest incidence of diarrhea as reported by patients. Conclusion: Bowel preparation with oral polyethylene glycol results in higher degree of bowel distension than with water or milk, but presents worst acceptance related to its taste and frequency of diarrhea as a side effect. (author)

  3. Computed tomography enterography: a comparison of different neutral oral contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    D' Ippolito, Giuseppe, E-mail: giuseppe_dr@uol.com.br [Department of Imaging Diagnosis, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, SP (Brazil); Braga, Fernanda Angeli; Resende, Marcelo Cardoso; Bretas, Elisa Almeida Sathler; Nunes, Thiago Franchi; Rosas, George de Queiroz; Tiferes, Dario Arie [Abdominal Imaging Section, Department of Imaging Diagnosis - Universidade Federal de Sao Paulo (Unifesp), Sao Paulo, SP (Brazil)

    2012-05-15

    Objective: The purpose of this study was to assess the performance of neutral oral contrast agents, comparing intestinal distension, distinction of intestinal wall, acceptance and side effects. Materials and Methods: Prospective, randomized, and double-blinded study involving 30 patients who underwent computed tomography of abdomen and pelvis with administration of neutral oral contrast agents, divided into three groups according the contrast agent type: milk, water, and polyethylene glycol. The images were consensually analyzed by two observers, considering the degree of bowel distension and intestinal wall distinction. The patients responded to a questionnaire regarding the taste of the ingested solution and on their side effects. Kruskal-Wallis and chi-square tests were employed for statistical analysis. Results: Among 40 studied intestinal segments, appropriate bowel distension (intestinal loop diameter > 2 cm) was observed in 14 segments (35%) in the milk group, 10 segments (25%) in the water group and 23 segments (57%) in the polyethylene glycol group (p = 0.01). Preparation with polyethylene glycol resulted in the best bowel distension, but it presented the worst taste and highest incidence of diarrhea as reported by patients. Conclusion: Bowel preparation with oral polyethylene glycol results in higher degree of bowel distension than with water or milk, but presents worst acceptance related to its taste and frequency of diarrhea as a side effect. (author)

  4. Combined oral contraceptives in polycystic ovary syndrome - indications and cautions.

    Science.gov (United States)

    Bozdag, Gurkan; Yildiz, Bulent Okan

    2013-01-01

    Combined oral contraceptive pills (OCPs) have been used in women with polycystic ovary syndrome (PCOS) for the treatment of menstrual disorders, acne and hirsutism. Despite years of their use and broad clinical experience, there are still ongoing doubts concerning their implications for the cardiovascular system and carbohydrate metabolism both in the general population and women with PCOS. In the general population, the risk of venous thromboembolism is reported to be increased. However, arterial thrombotic events seem to require concomitant risk factors to appear during administration of OCPs. In terms of carbohydrate metabolism, available data do not consistently suggest an increased risk of impaired glucose tolerance (IGT) or conversion of IGT to type 2 diabetes mellitus, in spite of some subtle fluctuations in glucose and insulin levels. In subgroup analyses of epidemiological studies in the general population, there is no finding indicating an increased risk of cardiovascular disease and related mortality in premenopausal women with PCOS. There is no significant alteration in carbohydrate and lipid metabolism after use of OCP in PCOS either. The absence of further cardiometabolic risk with OCP use in PCOS might suggest some unproven preventive alterations in this patient population. Copyright © 2013 S. Karger AG, Basel.

  5. Ct enterography/ct abdomen and pelvis using neutral oral contrast. a new combination of natural products

    International Nuclear Information System (INIS)

    Aslam, M.O.

    2014-01-01

    Our purpose was to assess the performance of a new combination of neutral oral contrast for CT abdomen and CT Enterography in comparison with commercially available neutral oral contrast VoLumen. Seventy three consecutive patients were given sorbitol/CMC (Carboxy Methyl Cellulose) solution or VoLumen as oral contrast agent for abdominal computed tomography (CT) scan. 23 patients were male and 37 females. Age range was between 16 and 67 years. Since the use of CT scan for abdominal pathologies, there was need to separate bowel loops to localize the pathology. Three types of oral contrast can be used in CT-Scan abdomen; Positive, Neutral and negative. The above used contrasts are Neutral contrast these refers to agents that have an attenuation value similar to that of water (0-30 H).Our results show this new combination of Cc and Sorbitol to be equally good as VoLumen, for luminal distension and mural details, in duodenum and jejunum. While better than VoLumen for Ileal distension. (author)

  6. Combination treatment of oral terbinafine with topical terbinafine and 10% urea ointment in hyperkeratotic type tinea pedis.

    Science.gov (United States)

    Shi, Tian-Wei; Zhang, Jiang-An; Zhang, Xian-Wei; Yu, Hong-Xing; Tang, Yong-Bo; Yu, Jian-Bin

    2014-09-01

    Hyperkeratotic-type tinea pedis is chronic and recalcitrant to topical antifungal agents. Some topical antifungal agents are effective; however, long duration of therapy is required, which often reduce the treatment compliance of patients. To seek for short period therapy of hyperkeratotic type tinea pedis, in this study, we observed the efficacy and safety of treatment of topical terbinafine and 10% urea ointment combined oral terbinafine. Participants with hyperkeratotic type tinea pedis were randomly assigned to two groups. Patients in group I were treated with oral terbinafine for 2 weeks and topical terbinafine and 10% urea ointment for 4 weeks, whereas in group II, only the above topical agents were applied for 12 weeks. Clinical improvement rates and fungal eradication rates were compared between the two groups at 24 weeks after the initiation of treatment. The group I had stopped the topical therapy 8 weeks earlier than group II. There were no significant differences in mycological eradication rates and clinical improvement rates between the two groups, besides, no major side effects were noted in both groups. The short combination therapy with oral terbinafine was effective and safe; it should be a valuable option for patients with hyperkeratotic type tinea pedis. © 2014 Blackwell Verlag GmbH.

  7. Combined oral contraceptives : the risk of myocardial infarction and ischemic stroke

    NARCIS (Netherlands)

    Roach, Rachel E J; Helmerhorst, Frans M.; Lijfering, Willem M.; Stijnen, Theo; Algra, Ale; Dekkers, Olaf M.

    2015-01-01

    BACKGROUND: Combined oral contraceptives (COCs) have been associated with an increased risk of arterial thrombosis, i.e. myocardial infarction or ischemic stroke. However, as these diseases are rare in young women and as many types of combined oral contraception exist, the magnitude of the risk and

  8. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    OpenAIRE

    Mihir Kothari

    2014-01-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  9. Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

    Science.gov (United States)

    Kothari, Mihir

    2014-12-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  10. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    Directory of Open Access Journals (Sweden)

    Mihir Kothari

    2014-01-01

    Full Text Available Part time occlusion therapy is not reported to cause occlusion (reverse amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  11. Pharmacodynamics of combined estrogen-progestin oral contraceptives: 1. Effects on metabolism.

    Science.gov (United States)

    Bastianelli, Carlo; Farris, Manuela; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

    2017-03-01

    The risk-benefit profile of any pharmacologic agent must be evaluated against risks connected with the events to be avoided. This is especially true in the case of hormonal contraception, not intended to combat a disease. Over the six decades during which their use has progressively expanded, the risk-benefit profile of combined oral contraceptives (COC) has substantially changed, with new combinations, dosages and mode of administration appearing on the market. Area covered: In a series of articles, recent information on the complex issue of COC risks and benefits will be reviewed in the hope of providing an updated picture. The present article reviews metabolic changes occurring during use of modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), often compared to classic compounds, such as levonorgestrel. Three categories of metabolic effects in healthy women are detailed: on carbohydrates, lipid and bone mineral content. Expert commentary: Overall, the picture is reassuring: the new generations of progestins are basically devoid of androgenic, estrogenic or glucocorticoid related side-effects. This should result in an improved safety profile, although past history teaches us that that large comparative and surveillance studies are required before firm conclusions can be drawn. At any rate, available evidence indicates that metabolic effects of third and fourth generation progestins, especially when they are combined with natural estrogens, are minimal and, if used in healthy women, should not cause concern.

  12. Human-Agent Decision-making: Combining Theory and Practice

    Directory of Open Access Journals (Sweden)

    Sarit Kraus

    2016-06-01

    Full Text Available Extensive work has been conducted both in game theory and logic to model strategic interaction. An important question is whether we can use these theories to design agents for interacting with people? On the one hand, they provide a formal design specification for agent strategies. On the other hand, people do not necessarily adhere to playing in accordance with these strategies, and their behavior is affected by a multitude of social and psychological factors. In this paper we will consider the question of whether strategies implied by theories of strategic behavior can be used by automated agents that interact proficiently with people. We will focus on automated agents that we built that need to interact with people in two negotiation settings: bargaining and deliberation. For bargaining we will study game-theory based equilibrium agents and for argumentation we will discuss logic-based argumentation theory. We will also consider security games and persuasion games and will discuss the benefits of using equilibrium based agents.

  13. Management of Antithrombotic Agents in Oral Surgery Maria Martinez and Dimitrios A. Tsakiris *

    Directory of Open Access Journals (Sweden)

    Maria Martinez

    2015-10-01

    Full Text Available Systemic anticoagulation with intravenous or oral anticoagulants and antiplatelet agents is an efficient treatment against thromboembolic or cardiovascular disease. Invasive dental procedures or oral surgery might be associated with bleeding complications if carried out under anticoagulants. Patients on vitamin K antagonists, new direct anticoagulants or antiplatelet agents having dental interventions with low-risk for bleeding do not need interruption of anticoagulation. In case of bleeding complications local hemostatic measures, such as local surgical sutures, fibrin glue, local antifibrinolytic treatment with tranexamic acid, or e-aminocaproic acid suffice to stop bleeding. In patients with high risk of bleeding an individual assessment of the benefit/risk ratio of interrupting anticoagulation should be carried out. Bridging the long-term anticoagulation with short-term anticoagulants should be planned according to national or international guidelines. The introduction of the newer direct oral anticoagulants having more flexible pharmacokinetic properties has facilitated bridging, allowing short-term interruption without increasing the risk of relapsing thrombotic or cardiovascular events.

  14. Shifting to a non-vitamin K antagonist oral anticoagulation agent from vitamin K antagonist in atrial fibrillation

    DEFF Research Database (Denmark)

    Fosbøl, Emil L; Vinding, Naja Emborg; Lamberts, Morten

    2017-01-01

    Aims: After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran...

  15. Inner conflict in patients receiving oral anticancer agents: a qualitative study.

    Science.gov (United States)

    Yagasaki, Kaori; Komatsu, Hiroko; Takahashi, Tsunehiro

    2015-04-14

    To explore the experiences of patients receiving oral anticancer agents. A qualitative study using semistructured interviews with a grounded theory approach. A university hospital in Japan. 14 patients with gastric cancer who managed their cancer with oral anticancer agents. Patients with cancer experienced inner conflict between rational belief and emotional resistance to taking medication due to confrontation with cancer, doubt regarding efficacy and concerns over potential harm attached to use of the agent. Although they perceived themselves as being adherent to medication, they reported partial non-adherent behaviours. The patients reassessed their lives through the experience of inner conflict and, ultimately, they recognised their role in medication therapy. Patients with cancer experienced inner conflict, in which considerable emotional resistance to taking their medication affected their occasional non-adherent behaviours. In patient-centred care, it is imperative that healthcare providers understand patients' inner conflict and inconsistency between their subjective view and behaviour to support patient adherence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Cost-effectiveness of oral antiplatelet agents--current and future perspectives.

    Science.gov (United States)

    Arnold, Suzanne V; Cohen, David J; Magnuson, Elizabeth A

    2011-08-09

    Cardiovascular disease is both highly prevalent and exceedingly costly to treat. Several novel antiplatelet agents have been found to be effective in reducing the morbidity and mortality associated with cardiovascular disease. Understanding both the economic and the clinical implications of these novel therapies is particularly important. In this article, the results of published evaluations of the cost-effectiveness of oral antiplatelet strategies for use across a range of clinical conditions and treatment settings are reviewed. The results of these studies support the use of aspirin for primary prevention in high-risk patients and for secondary prevention in all patients with previous cardiovascular events. Although the optimal duration of dual antiplatelet therapy after an event remains uncertain, favorable cost-effectiveness estimates have been demonstrated for aspirin plus clopidogrel versus aspirin alone after a myocardial infarction or percutaneous coronary intervention. Moreover, prasugrel has been shown to be more cost-effective than clopidogrel for patients with an acute coronary syndrome and planned percutaneous coronary intervention. As novel antiplatelet agents emerge and existing agents are tested in different patient populations, the evaluation of the relative economic efficiency of these oral antiplatelet treatment strategies will continue to be instrumental to optimally inform clinical and health-policy decision-making.

  17. Barium sulfate suspension as a negative oral contrast agent for MR imaging

    International Nuclear Information System (INIS)

    Li, K.C.P.; Tart, R.P.; Fitzsimmons, J.R.; Storm, B.; Mao, J.

    1989-01-01

    Proton spectroscopy with linewidth measurements and MR imaging were performed on various commercially available barium sulfate suspensions as well as inorganic sulfates and barium salts. Approximately 500 mL of 20%, 40%, 60%, and 70% wt/wt single-contrast oral barium sulfate suspensions were administered to four normal volunteers, and MR imaging was performed with both a 1.5-T and a 0.15-T MR imager. As much as 80% of the small bowel and the entire colon were well visualized with the 60% or 70% wt/wt single-contrast barium sulfate suspensions. The authors conclude that barium sulfate suspensions are useful as oral MR contrast agents

  18. Oral contrast agents for small bowel distension in MRI: influence of the osmolarity for small bowel distention

    International Nuclear Information System (INIS)

    Ajaj, Waleed; Kuehle, Christiane; Nuefer, Michael; Goehde, Susanne C.; Lauenstein, Thomas C.; Goyen, Mathias; Schneemann, Hubert; Ruehm, Stefan G.

    2005-01-01

    To assess the effect of the osmolarity for small bowel distension in MRI, ten volunteers ingested at two separate occasions negative oral contrast agents with different quantity and osmolarity: (1) a water solution combined with 2.0% sorbitol and 0.2% locus bean gum (LBG) with a quantity of 1500 ml and an osmolarity of 148 mOsmol/l, (2) a water solution combined with 2.0% sorbitol and 2.0% barium sulphate with a quantity of 1000 ml and an osmolarity of 194 mOsmol/l. Small bowel distension was quantified on coronal 2D-TrueFISP images by measuring the small bowel diameters. There were no statistically significant differences in mean small bowel diameter between both contrast agents. The mean small bowel distension was 19.2 mm after ingestion of 1500 ml of sorbitol-LBG solution and 19.0 mm after ingestion of 1000-ml sorbitol-barium sulphate solution. Furthermore, all volunteers found the ingestion of 1000-ml solution more pleasant than the 1500-ml solution. The ingestion of 1000 ml of sorbitol-barium sulphate solution led to a sufficient small bowel distension compared to 1500 ml of sorbitol-LBG solution. The side effect rate of both solutions was low. Based on these data, we recommend a quantity of 1000 ml of sorbitol-barium sulphate solution as an alternative for 1500-ml sorbitol-LBG solution for optimal bowel distension. (orig.)

  19. Combination of chemotherapy, radiotherapy and surgery in the treatment of oral cancer

    International Nuclear Information System (INIS)

    Ayyagiri, S.; Gupta, B.D.; Dutta, T.K.

    1980-01-01

    In locally advanced oral cancer, the main modalities of treatment, e.g. surgery and radiotherapy, most often fail to control the disease when used singly. A combination policy of surgery and radiotherapy achieves adequate control of the disease. In order to improve the results in advanced oral cancer, chemotherapy given prior to and during radiation treatment and judicious combination of surgery offer the best possible approach in the management. The experience in the combination policy in the treatment of oral cancer in Northern India is dealt with. (auth.)

  20. Circumvention of inherent or acquired cytotoxic drug resistance in vitro using combinations of modulating agents.

    Science.gov (United States)

    Cadagan, David; Merry, Stephen

    2013-10-01

    Modulating agents are used to circumvent drug resistance in the clinical setting. However achievable serum concentrations are often lower than those which are optimal in vitro. Combination of modulating agents with non-overlapping toxicities may overcome this obstacle. We have investigated combinations of three modulating agents (quinine, verapamil, and cinnarizine) to circumvent inherent or acquired resistance to the cytotoxic drugs doxorubicin, vincristine and paclitaxel. Dose-response curves to cytotoxic drugs in the presence/absence of modulating agents were determined using colony formation and cell proliferation assays. Doxorubicin accumulation into cell monolayers was measured by fluorescence spectrophotometry. Greater (1.9-fold) sensitisation to particular cytotoxic drugs was observed for certain combinations of modulating agents compared to individual effects. The most effective combination was quinine-plus-verapamil with the cytotoxic drug doxorubicin. This increase in sensitivity was associated with increased doxorubicin accumulation. Such enhanced activity was, however, not observed for all combinations of modulating agents or for all studied cytotoxic drugs. The findings of the present study suggest certain combinations of modulating agents to have a clinical role in circumventing drug resistance. Particular combinations of modulating agents must be carefully chosen to suit particular cytotoxic drug treatments.

  1. Combination therapy of potential gene to enhance oral cancer therapeutic effect

    Science.gov (United States)

    Yeh, Chia-Hsien; Hsu, Yih-Chih

    2015-03-01

    The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

  2. Evaluation of date syrup as an oral negative contrast agent for MRCP.

    Science.gov (United States)

    Govindarajan, Arunkumar; Lakshmanan, Prakash Manikka; Sarawagi, Radha; Prabhakaran, Velu

    2014-11-01

    The purpose of this study was to compare the in vitro effects of date syrup with those of other contrast agents by qualitative and quantitative analysis and in vivo evaluation of the use of date syrup to improve the quality of MRCP images. Phantoms containing date syrup, ferumoxsil, pineapple juice, and water were imaged by 1.5-T MRI with T2-weighted and MRCP sequences, and signal-to-noise ratios were calculated. Biochemical analysis of date syrup was performed to find the nature of iron in it, and the iron content was quantified by energy-dispersive x-ray spectroscopy. Sixty patients underwent MRCP before and 30 minutes after ingestion of 100 mL of date syrup. Unenhanced and contrast-enhanced images were scored for gastrointestinal tract signal suppression and visualization of various pancreaticobiliary structures. In vitro evaluation showed that images obtained with date syrup had a signal-to-noise ratio comparable to that of images obtained with ferumoxsil in T2-weighted and MRCP sequences. The iron concentration in date syrup was 2.6 mg/dL, and it was in ferric form. Images obtained after oral contrast administration had statistically significant improvement in gastrointestinal tract signal suppression (p Date syrup can be used as a negative oral contrast agent for gastrointestinal tract signal suppression during MRCP and for improving visualization of various pancreaticobiliary structures.

  3. The Usage of Oral Anti Hyperglycemic Agent in Gestational Diabetes: Pros and Cons

    Directory of Open Access Journals (Sweden)

    Bram Pradipta

    2014-06-01

    Full Text Available The prevalence of gestational diabetes mellitus (GDM  is increasing as the pregnant population becomes older and more obese. Fifteen percent of GDM patients require medical intervention. Insulin is still the drug of choice because it has not been implicated as a teratogen in human pregnancies.Insulin has its disadvantages such as the need for injections, the risk of hypoglycaemia, excessive weight gain and the costs. The use of oral anti hyperglicemic agent (OAHA, traditionally contraindicated, now can be considered as an alternative for insulin which can be beneficial in developing countries. From four groups of OAHA, sulfonylurea and biguanides can be used during pregnancy. Studies and randomized controlled trial (RCT have been done and most summarized that it does not increase any maternal and perinatal morbidity. Most data also show that thereare also no differences in glycemic control or pregnancy outcomes compared with insulin. There are conflicting data shows metformin increase prevalence of preeclampsia patient and perinatal morbidity. OAHA usage, although not yet recommended internationally, can be considered in GDMpatients with uncontrolled blood sugar levels that require medical intervention but can not use insulin. Wellconducted, prospective, controlled studies regarding itsfeasibility in pregnant women with diabetes are still needed.Keywords:oral antihyperglycemic agent, gestational, diabetes

  4. In vitro evaluation of alternative oral contrast agents for MRI of the gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Babos, Magor [University of Szeged, Faculty of Science (Hungary); Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: babosmagor@yahoo.com; Schwarcz, Attila [University of Pecs, Department of Neurosurgery, Pecs Diagnostic Institute, 7624 Pecs, Retu. 2 (Hungary)], E-mail: attila.schwarcz@aok.pte.hu; Randhawa, Manjit Singh [University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: majyaal@hotmail.com; Marton, Balazs [University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: balazsmarton@freemail.hu; Kardos, Lilla [Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: medlis@tiszanet.hu; Palko, Andras [Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary); University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: palko@radio.szote.u-szeged.hu

    2008-01-15

    Purpose: In vitro evaluation of different materials as potential alternative oral contrast agents for small bowel MRI. Materials and methods: The T1 and T2 relaxation times of rose hip syrup, black currant extract, cocoa, iron-deferoxamine solution and a commonly used oral contrast material (1 mM Gd-DTPA) were determined in vitro at different concentrations on a 1.0 T clinical MR scanner. T1 values were obtained with an inversion prepared spoiled gradient echo sequence. T2 values were obtained using multiple echo sequences. Finally the materials were visualized on T1-, T2- and T2*-weighted MR images. Results: The relaxation times of the undiluted rose hip syrup (T1 = 110 {+-} 5 ms, T2 = 86 {+-} 3 ms), black currant extract (T1 = 55 {+-} 3 ms, T2 = 39 {+-} 2 ms) and 5 mM iron-deferoxamine solution (T1 = 104 {+-} 4 ms, T2 = 87 {+-} 2 ms) were much shorter than for a 1 mM Gd-DTPA solution (T1 = 180 {+-} 8 ms, T2 = 168 {+-} 5 ms). Dilution of black currant extract to 30% or a 3 mM iron-deferoxamine solution conducted to T1 relaxation times which are quite comparable to a 1 mM Gd-DTPA solution. Despite its much lower metal content an aqueous cocoa suspension (100 g/L) produced T2 relaxation times (T1 = 360 {+-} 21 ms, T2 = 81 {+-} 3 ms) more or less in the same range like the 5 mM iron-deferoxamine solution. Imaging of our in vitro model using clinical sequences allowed to anticipate the T1-, T2- and T2*-depiction of all used substances. Cocoa differed from all other materials with its low to moderate signal intensity on T1- and T2-weighted sequences. While all substances presented a linear 1/T1 and 1/T2 relationship towards concentration, rose hip syrup broke ranks with a disproportionately high increase of relaxation at higher concentrations. Conclusions: Rose hip syrup, black currant extract and iron-deferoxamine solution due to their positive T1 enhancement characteristics and drinkability appear to be valuable oral contrast agents for T1-weighted small bowel MRI

  5. In vitro evaluation of alternative oral contrast agents for MRI of the gastrointestinal tract

    International Nuclear Information System (INIS)

    Babos, Magor; Schwarcz, Attila; Randhawa, Manjit Singh; Marton, Balazs; Kardos, Lilla; Palko, Andras

    2008-01-01

    Purpose: In vitro evaluation of different materials as potential alternative oral contrast agents for small bowel MRI. Materials and methods: The T1 and T2 relaxation times of rose hip syrup, black currant extract, cocoa, iron-deferoxamine solution and a commonly used oral contrast material (1 mM Gd-DTPA) were determined in vitro at different concentrations on a 1.0 T clinical MR scanner. T1 values were obtained with an inversion prepared spoiled gradient echo sequence. T2 values were obtained using multiple echo sequences. Finally the materials were visualized on T1-, T2- and T2*-weighted MR images. Results: The relaxation times of the undiluted rose hip syrup (T1 = 110 ± 5 ms, T2 = 86 ± 3 ms), black currant extract (T1 = 55 ± 3 ms, T2 = 39 ± 2 ms) and 5 mM iron-deferoxamine solution (T1 = 104 ± 4 ms, T2 = 87 ± 2 ms) were much shorter than for a 1 mM Gd-DTPA solution (T1 = 180 ± 8 ms, T2 = 168 ± 5 ms). Dilution of black currant extract to 30% or a 3 mM iron-deferoxamine solution conducted to T1 relaxation times which are quite comparable to a 1 mM Gd-DTPA solution. Despite its much lower metal content an aqueous cocoa suspension (100 g/L) produced T2 relaxation times (T1 = 360 ± 21 ms, T2 = 81 ± 3 ms) more or less in the same range like the 5 mM iron-deferoxamine solution. Imaging of our in vitro model using clinical sequences allowed to anticipate the T1-, T2- and T2*-depiction of all used substances. Cocoa differed from all other materials with its low to moderate signal intensity on T1- and T2-weighted sequences. While all substances presented a linear 1/T1 and 1/T2 relationship towards concentration, rose hip syrup broke ranks with a disproportionately high increase of relaxation at higher concentrations. Conclusions: Rose hip syrup, black currant extract and iron-deferoxamine solution due to their positive T1 enhancement characteristics and drinkability appear to be valuable oral contrast agents for T1-weighted small bowel MRI. Cocoa with its

  6. Effect of low zinc intake and oral contraceptive agents on nitrogen utilization and clinical findings in young women.

    Science.gov (United States)

    Hess, F M; King, J C; Margen, S

    1977-12-01

    In a previous paper we reported that serum, urine and fecal zinc levels fell markedly in women taking a combination oral contraceptive agent (+OCA) and in women with normal menstrual cycles (-OCA) when they consumed a low-zinc diet (less than 0.2 mg/day) for 35 days. We evaluated other biochemical and clinical data in order to determine if depletion of accessible body zinc and/or physiologic adjustment to conserve body zinc stores had occurred. Neither low zinc intake nor oral contraceptive use appeared to influence nitrogen balance or body weight. Use of contraceptive drugs appeared to influence the response of blood parameters to zinc depletion. Serum transferrin and cholesterol declined significantly in the -OCA group, whereas alkaline phosphatase and gamma-globulin changed significantly in both groups. Clinical problems developed in all the subjects with serum zinc levels below 50 microgram/dl during the study; three of the six with serum zinc levels above 50 microgram/dl also complained of clinical symptoms. The results suggest that zinc deficiency through depletion of accessible body zinc stores developed during the 35-day study.

  7. Neoadjuvant polychemotherapy in combined treatment for oral cavity mucosa carcinoma patients

    International Nuclear Information System (INIS)

    Protsyk, V.S.; Trembach, A.M.; Korobko, E.V.; Garbar, L.I.

    2007-01-01

    Neoadjuvant polychemotherapy and radiotherapy as a pre surgeon combined treatment was applied to 144 patients with cancer of oral cavity mucosa. That method of treatment permit to obtain maximum destroy of tumoral parenchyma and clinical effect to all patients. (authors)

  8. Penetration of topical, oral, and combined administered ofloxacin into the subretinal fluid

    OpenAIRE

    Cekic, O.; Batman, C.; Yasar, U.; Totan, Y.; Basci, N.; Bozkurt, A.; Zilelioglu, O.; Kayaalp, S

    1999-01-01

    AIMS—To assess the subretinal fluid (SRF) levels of ofloxacin following topical, oral or combined administration.
METHODS—31 patients undergoing conventional retinal reattachment surgery were randomly assigned to three groups. Nine patients received topical ofloxacin, 11 patients received oral ofloxacin, and the other 11 patients received combined administration. Collected SRF samples were analysed for drug level by using high performance liquid chromatography.
RESULTS—SRF drug levels after o...

  9. Sustained release of a novel anti-quorum-sensing agent against oral fungal biofilms.

    Science.gov (United States)

    Feldman, Mark; Shenderovich, Julia; Al-Quntar, Abed Al Aziz; Friedman, Michael; Steinberg, Doron

    2015-04-01

    Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. ORAL HYPOGLYCAEMIC AGENTS IN THE MANAGEMENT OF TYPE II DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Durgaprasad M.

    2016-06-01

    Full Text Available OBJECTIVES Diabetes is fast gaining the status of a potential epidemic globally. The number of people with diabetes has risen from 108 million in 1980 to 422 million in 2014, the rise seen more rapidly in developing and under developed countries. Type 2 Diabetes Mellitus (T2DM being the most common type, accounting for an estimated 85-95% of all diabetes cases. Diabetes remains a major cause of blindness, renal failure, and cardiovascular events including heart attacks, stroke and limb amputations. 1 Being an heterogeneous disorder, many adults with T2DM have difficulty controlling their blood sugar levels and associated complications as most of available antidiabetic agents aim to achieve only normoglycaemia and relieve diabetes symptoms, such as polydipsia, polyuria, weight loss, ketoacidosis while the longterm goals to prevent the development of or slow the progression of longterm complications of the disease is often unaddressed, therefore, there remains, a significant unmet demand for new agents that will help diabetic patients achieve treatment targets without increasing the risk for weight gain or hypoglycaemia. Among the new classes of oral agents, SGLT-2 inhibitors and mTOT insulin sensitisers appear to hold some good promise. However, recent articles published describing its adverse effect profile of SGLT-2 inhibitors had put a question mark on its utility. In this article, we have reviewed the plethora of available OHAs along with the newer OHAs for managing T2DM optimally.

  11. Oral gadopentetate dimeglumine administration as a negative gastrointestinal contrast agent to improve image quality of MR cholangiopancreatography

    International Nuclear Information System (INIS)

    Chen Yi; Xu Yikai; Zhao Yuhui; Wang Guisheng

    2008-01-01

    Objective: To choose optimal concentration and volume of Gd-DTPA solution as a oral gastrointestinal negative contrast agent for MRCP. To evaluate the role of Gd-DTPA solution in improving image quality of MRCP. Methods: In vitro experiment: Gd-DTPA solution was made with different concentrations. T 1 WI, T 2 WI, two-dimensional single slice fast spin echo sequence and three-dimensional half-fourier acquisition single-shot fast spin echo sequence were performed to measure the signal intensity of these contrast agents respectively, so Gd-DTPA solution with the optimal concentration can be decided as oral negative gastrointestinal contrast agent on MRCP. Clinical study: The Gd-DTPA solution with optimal concentration and volume was regarded as an oral negative gastrointestinal contrast agent of MRCP. Twenty- four' patients were performed with MRCP before and after (5-10 minutes and 10-15 minutes) administration of oral negative gastrointestinal contrast agent and image quality was analyzed. Statistical analysis was performed using analysis of variance with SPSS 10.0. Results: When the concentration of Gd-DTPA solution was ≤0.01 mol/L, the contrast agent was hyperintense on T 1 WI. On T 2 WI, when the concentration was ≥0.015 mol/L, it was as hypointense as basic ground; On 2D FSE MRCP images, controls were hyperintense and the contrast agent with concentration ranging from 0.0025 mol/L to 0.03 mol/L was hypointense. On 3D HEAST MRCP image, controls were hyperintense and when the concentration of Gd-DTPA was ≥0.01 mol, the contrast agent was hypointense. The Gd-DTPA solution with the concentration of 0.01 mol/L and the volume of 100 ml was chosen as MRCP oral negative gastrointestinal contrast agent. On MRCP images after oral administration of the contrast agent, in 10-15 minutes, the average grade scores within 24 patients of the intrahepatic bile duct, the common hepatic bile duct, the gall bladder, the common bile duct and pancreatic duct (the average grade

  12. Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

    International Nuclear Information System (INIS)

    Beal, Kathryn; Abrey, Lauren E; Gutin, Philip H

    2011-01-01

    Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

  13. Gastric stromal tumor: two-phase dynamic CT findings with water as oral contrast agents

    International Nuclear Information System (INIS)

    Lee, Se Hyo; Cho, June Sik; Shin, Kyung Sook; Jeong, Ki Ho; Park, Jin Yong; Yu, Ho Jun; Kim, Young Min; Jeon, Kwang Jin

    2000-01-01

    To evaluate two-phase dynamic CT with water as oral contrast agents in the CT diagnosis of gastric stromal tumors. We retrospectively reviewed the CT findings in 21 patients with pathologically proven gastric stromal tumors. Six were found to be benign, twelve were malignant, and there were three cases of STUMP (stromal tumor uncertain malignant potential). Two-phase dynamic CT scans with water as oral contrast agents were obtained 60-70 secs (portal phase) and 3 mins (equilibrium phase) after the start of IV contrast administration. We determined the size, growth pattern, and enhancement pattern of the tumors and overlying mucosa, the presence or absence of ulceration and necrosis, tumor extent, and lymph nod and distant metastasis. The CT and pathologic findings were correlated. All six benign tumors and three STUMP were less than 5.5 cm in size, and during the portal phase showed round endogastric masses with highly enhanced, intact overlying mucosa. Twelve malignant tumors were 4.5-15.5 cm in size (mean, 11.5 cm); an endogastric mass was seen in three cases, an exogastric mass in one, and a mixed pattern in eight. On portal phase images the tumors were not significantly enhanced, but highly enhanced feeding vessels were noted in five larger tumors (greater than 10 cm). All 12 malignant tumors showed ulceration and necrosis, and interruption of overlying mucosa was clearly seen during the portal phase. We were readily able to evaluate tumor extent during this phase, and in ten malignant tumors there was no invasion of adjacent organs. Seven malignant tumors showed air density within their necrotic portion (p less than 0.05). On equilibrium phase images, all malignant tumors showed heterogeneous enhancement due to necrosis, and poorly enhanced overlying mucosa. Dynamic CT during the portal phase with water as oral contrast agents was useful for depicting the submucosal origin of gastric stromal tumors and for evaluating the extent of malignant stromal tumors. Our

  14. Synergistic combination therapy of antitumor agents, membrane modification agents and irradiation

    International Nuclear Information System (INIS)

    Watarai, Jiro; Itagaki, Takatomo; Akutsu, Thoru; Yamaguchi, Kouichi; Kato, Isao

    1983-01-01

    Larygeal cancer were treated with synergistic combination therapy of Futraful in suppository, vitamin A, cepharanthin and irradiation from April 1981 to June 1982. This combination therapy resulted in high percentage of the tumor regression in the case of the invading laryngeal cancer and negligible complication. (author)

  15. New Oral Hypoglycemic Agents and Cardiovascular Risk. Crossing the Metabolic Border.

    Science.gov (United States)

    Dalama, Belén; Mesa, Jordi

    2016-11-01

    Sodium-glucose cotransporter 2 inhibitors are a novel pharmacological class of oral hypoglycemic agents that lower glucose levels by increasing renal glucose excretion in an insulin-independent manner. However, this seemingly simple mechanism has more complex indirect metabolic effects. The results of randomized clinical trials have shown that these inhibitors effectively lower blood glucose and glycated hemoglobin levels without increasing the risk of hypoglycemia and, at the same time, also reduce bodyweight and systolic blood pressure. In this review, we describe the mechanism of action, efficacy, and safety of currently marketed drugs, as well as other risk factors besides glucose that can potentially be modulated positively. Recent data on empagliflozin showing a significant cardiovascular benefit have compelled us to update knowledge of this new therapeutic class for the treatment of type 2 diabetes. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Combining biological agents and chemotherapy in the treatment of cholangiocarcinoma

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Jakobsen, Anders

    2011-01-01

    is not always possible. Chemotherapy is effective and the combination of cisplatin and gemcitabine is considered a standard treatment of inoperable cholangiocarcinoma. Biological targeted treatment to date has minor effect when given as monotherapy, but some of the drugs hold promise as an adjunct...... to chemotherapy. It should, however, be noted that most of the trials are based on few patients, and thus far the literature does not allow for a conclusion as to the role of biological treatment on cholangiocarcinoma. This situation calls for well-designed randomized trials, and international cooperation as well...

  17. Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

    Science.gov (United States)

    Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

    2008-11-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation.

  18. Alteration of intestinal microbiota in mice orally administered with salmon cartilage proteoglycan, a prophylactic agent.

    Directory of Open Access Journals (Sweden)

    Krisana Asano

    Full Text Available Proteoglycan (PG extracted from salmon nasal cartilage has potential to be a prophylactic agent. Daily oral administration of the PG attenuates systemic inflammatory response in the experimental mouse models. In this study, we applied the culture-independent approach to investigate an alteration of intestinal microbiota composition in PG-administered mice. The results indicated that the population level of bacilli increased in the small and large intestine upon PG administration. On the other hand, the population level of clostridia decreased in the large intestine. The proportion of bacteria that are able to ferment saccharides and produce short-chain fatty acids increased in the small intestine and decreased in the large intestine. Importantly, population level of probiotic lactobacilli and bacteria exhibiting the immunomodulatory effect increased in the PG-administered mice. In addition, several disease-associated bacteria decreased upon PG administration. These results provided an understanding of the specific role of PG involved in host immune modulation and supported our hypothesis that daily oral administration of PG improves the overall balance in composition of the intestinal microbial community.

  19. In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent.

    Science.gov (United States)

    Tanio, T; Ichise, K; Nakajima, T; Okuda, T

    1990-06-01

    SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.

  20. Effect of oral antiseptic agents on phospholipase and proteinase enzymes of Candida albicans.

    Science.gov (United States)

    Uygun-Can, Banu; Kadir, Tanju; Gumru, Birsay

    2016-02-01

    Candida-associated denture stomatitis is the most prevalent form of oral candida infections among the denture wearers. Generally, antiseptic oral rinses used in the treatment of these infections are considered as an adjunct or alternative antifungal treatment. Studies have suggested that the intraoral concentrations of antiseptics decrease substantially to the sub-therapeutic levels on account of the dynamics of the oral cavity. This condition yields the question about the minimum antiseptic concentration that effect the character or pathogenesis of Candida during treatment. The extracellular phospholipase and proteinase enzymes of Candida albicans are regarded to have a crucial role in the pathogenesis of human fungal infections. Therefore, the aim of this study was to investigate the effect of different sub-therapeutic concentrations of chlorhexidine gluconate, hexetidine and triclosan on the production of these enzymes by C. albicans strains isolated from 20 patients with denture stomatitis. Phospholipase test was done by using Sabouraud dextrose agar with egg yolk, proteinase test was done by using bovine serum albumin agar. Phospholipase test was done by using Sabouraud dextrose agar with egg yolk, proteinase test was done by using bovine serum albumin agar. Exoenzyme production of 20 strains which were brief exposured to sub-therapeutic concentrations of three antiseptic agents decreased significantly compared with the strains that were not exposured with antiseptic values (pantiseptics (pantiseptic was compared, there were no significant differences between enzymatic activities (p>0.05). The results of this study show that sub-therapeutic levels of each antiseptic may modulate candidal exoenzyme production, consequently suppressing pathogenicity of C. albicans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Oral contraceptives induced hepatotoxicity

    OpenAIRE

    B. Akshaya Srikanth; V. Manisree

    2013-01-01

    Oral Contraceptives are the pharmacological agents used to prevent pregnancy. These are divided as the combined and progestogen methods and are administered orally, transdermally, systemically and via vaginal route. All these methods contain both oestrogen and progestogen. Vigorous usage of oral contraceptives and anabolic steroids as associated with cholestasis, vascular lesions and hepatic neoplasm. Benign hepatic neoplasms are clearly associated with oral contraceptives. In this article we...

  2. Advances in radioprotection through the use of combined agent regimens

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, J F; Kumar, K S; Walden, T L; Neta, R; Landauer, M R; Clark, E P [Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)

    1990-04-01

    Improved radioprotection and reduced lethal toxicity of the phosphorothioate WR 2721 was observed after administration with metals (selenium, zinc or copper). A number of receptor-mediated protectors and other biological compounds, including endotoxin, eicosanoids and cytokines, have at least an additive effect when administered with thiol protectors. Eicosanoids and other bioactive lipids must be administered before exposure, whereas some immunomodulators have activity when administered either before or after exposure, e.g. interleukin administered simultaneously with WR 2721 before or after irradiation enhances the efficacy of WR 2721. The most effective single or combinations of protectors result in a decrement in locomotor activity (index of behavioural toxicity). Recent evidence indicates that caffeine mitigates toxicity of an effective dose of phosphorothioate WR 3689 without altering its efficacy. (UK).

  3. Bioadhesive agents in addition to oral contrast media - evaluation in an animal model

    International Nuclear Information System (INIS)

    Conrad, R.; Schneider, G.; Textor, J.; Schild, H.H.; Fimmers, R.

    1998-01-01

    Purpose: To evaluate the additional effect of bioadhesives in combination with iotrolan and barium as oral contrast media in an animal model. Method: The bioadhesives Noveon, CMC, Tylose and Carbopol 934 were added to iotrolan and barium. The solutions were administered to rabbits by a feeding tube. The animals were investigated by computed tomography (CT) and radiography after 0,5, 4, 12, 24 and in part after 48 hours. Mucosal coating and contrast filling of the bowel were evaluated. Results: Addition of bioadhesives to oral contrast media effected long-term contrast in the small intestine and colon, but no improvement in continuous filling and coating of the gastrointestinal tract was detected. Mucosal coating was seen only in short regions of the caecum and small intestine. In CT the best results for coating were observed with tylose and CMC, in radiography additionally with carbopol and noveon. All contrast medium solutions were well tolerated. Conclusion: The evaluated contrast medium solutions with bioadhesives have shown long-term contrast but no improvement in coating in comparison to conventional oral contrast media. (orig.) [de

  4. Abolishing coinsurance for oral antihyperglycemic agents: effects on social insurance budgets.

    Science.gov (United States)

    Athanasakis, Kostas; Skroumpelos, Anastasis G; Tsiantou, Vassiliki; Milona, Katerina; Kyriopoulos, John

    2011-02-01

    To assess the effects of abolishing coinsurance for oral antihyperglycemic agents (OAAs) on the social insurance fund budget in Greece. A mathematical model estimating the effect of a decrease in patient coinsurance rate on demand for and adherence to OAAs and the subsequent clinical and economic outcomes. Price elasticity of demand for antidiabetic agents was used to estimate quantity demand change as a result of a coinsurance rate decrease and consequent increased adherence to OAAs. Given the inverse relationship between OAA adherence and glycated hemoglobin (A1C) level, the model calculated the mean decrease in A1C level and associated cost savings based on the cost difference between patients with controlled versus uncontrolled A1C levels. A decrease in patient coinsurance rate from 25% to 0% led to an incremental increase in OAA adherence of 30.5% and a mean decrease in A1C level of 0.6%. The A1C level decrease contributed to an 18.5% "shift" of uncontrolled patients to controlled A1C levels (<7%), which in economic terms translated into savings of 324 euro per patient over a 3-year period and an investment return rate of 122.8%. A series of 1-way and 2-way sensitivity analyses were conducted to verify the robustness and validity of the outcomes. The introduction of policies aimed at abolishing coinsurance for OAAs can result in improved patient outcomes and cost savings for the healthcare system.

  5. The combination of sodium perborate and water as intracoronal teeth bleaching agent

    Directory of Open Access Journals (Sweden)

    Ananta Tantri Budi

    2008-12-01

    Full Text Available Background: The color change on post-endodontic treated teeth can be overcome by intracoronal tooth bleaching using walking bleach. Some agents used in walking bleach are combination of sodium peroxide and hydrogen peroxide, and combination of sodium perborate and water. Purpose: The objective of this review is to provide information and consideration of using safe and effective bleaching agents in the field of dentistry. Reviews: On one side, the use of sodium perborate and water combination does not cause the reduction of dentin hardness, enamel decay, and root resorbtion. On the other side, the use of sodium perborate and 30% hydrogen peroxide combination indicates that it takes longer time in yielding the proper color of teeth. Conclusion: The use of sodium perborate and water combination as bleaching agents is effective and safe.

  6. Combined compared to dissociated oral and intestinal sucrose stimuli induce different brain hedonic processes

    Science.gov (United States)

    Clouard, Caroline; Meunier-Salaün, Marie-Christine; Meurice, Paul; Malbert, Charles-Henri; Val-Laillet, David

    2014-01-01

    The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggered by oral and/or intestinal sucrose sensing in pigs. Seven animals underwent brain single photon emission computed tomography (99mTc-HMPAO) further to oral stimulation with neutral or sucrose artificial saliva paired with saline or sucrose infusion in the duodenum, the proximal part of the intestine. Oral and/or duodenal sucrose sensing induced differential cerebral blood flow changes in brain regions known to be involved in memory, reward processes and hedonic (i.e., pleasure) evaluation of sensory stimuli, including the dorsal striatum, prefrontal cortex, cingulate cortex, insular cortex, hippocampus, and parahippocampal cortex. Sucrose duodenal infusion only and combined sucrose stimulation induced similar activity patterns in the putamen, ventral anterior cingulate cortex and hippocampus. Some brain deactivations in the prefrontal and insular cortices were only detected in the presence of oral sucrose stimulation. Finally, activation of the right insular cortex was only induced by combined oral and duodenal sucrose stimulation, while specific activity patterns were detected in the hippocampus and parahippocampal cortex with oral sucrose dissociated from caloric load. This study sheds new light on the brain hedonic responses to sugar and has potential implications to unravel the neuropsychological mechanisms underlying food pleasure and motivation. PMID:25147536

  7. A comparison of second and third generations combined oral contraceptive pills' effect on mood.

    Science.gov (United States)

    Shahnazi, Mahnaz; Farshbaf Khalili, Azizeh; Ranjbar Kochaksaraei, Fatemeh; Asghari Jafarabadi, Mohammad; Gaza Banoi, Kamal; Nahaee, Jila; Bayati Payan, Somayeh

    2014-08-01

    Most women taking combined oral contraceptives (COCs) are satisfied with their contraceptive method. However, one of the most common reasons reported for discontinuation of combined oral contraceptives (COCs) is mood deterioration. This study aimed to compare effects of the second and third generation oral contraceptive pills on the mood of reproductive women. This randomized, double-blind, controlled clinical trial was conducted in reproductive women at health centers in Tehran, Iran. Participants were randomized into the second and third generation oral contraceptive groups. Positive and negative moods were recorded using positive affect, negative affect scale (PANAS) tools at the end the second and fourth months of the study. Data analysis was carried out using ANOVA and P Values pills. The second generation oral contraceptive pills resulted in a decrease in positive mood (95% CI: 43.39 to 38.32 in second month and 43.39 to 26.05 in four month) and increase in negative mood (95% CI: 14.23 to 22.04 in second month and 14.23 to 32.26 in four month - P pills have a better effect on mood in women in reproductive ages than the second generation pills. It can be recommended as a proper combined oral contraceptive in Iran.

  8. A Comparison of Second and Third Generations Combined Oral Contraceptive Pills’ Effect on Mood

    Science.gov (United States)

    Shahnazi, Mahnaz; Farshbaf Khalili, Azizeh; Ranjbar Kochaksaraei, Fatemeh; Asghari Jafarabadi, Mohammad; Gaza Banoi, Kamal; Nahaee, Jila; Bayati Payan, Somayeh

    2014-01-01

    Background: Most women taking combined oral contraceptives (COCs) are satisfied with their contraceptive method. However, one of the most common reasons reported for discontinuation of combined oral contraceptives (COCs) is mood deterioration. Objectives: This study aimed to compare effects of the second and third generation oral contraceptive pills on the mood of reproductive women. Materials and Methods: This randomized, double-blind, controlled clinical trial was conducted in reproductive women at health centers in Tehran, Iran. Participants were randomized into the second and third generation oral contraceptive groups. Positive and negative moods were recorded using positive affect, negative affect scale (PANAS) tools at the end the second and fourth months of the study. Data analysis was carried out using ANOVA and P Values pills. The second generation oral contraceptive pills resulted in a decrease in positive mood (95% CI: 43.39 to 38.32 in second month and 43.39 to 26.05 in four month) and increase in negative mood (95% CI: 14.23 to 22.04 in second month and 14.23 to 32.26 in four month - P pills have a better effect on mood in women in reproductive ages than the second generation pills. It can be recommended as a proper combined oral contraceptive in Iran. PMID:25389478

  9. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Saunders, Deborah P.; Epstein, Joel B.; Elad, Sharon; Allemano, Justin; Bossi, Paolo; van de Wetering, Marianne D.; Rao, Nikhil G.; Potting, Carin; Cheng, Karis K.; Freidank, Annette; Brennan, Michael T.; Bowen, Joanne; Dennis, Kristopher; Lalla, Rajesh V.

    2013-01-01

    The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. A systematic review of the available literature was conducted. The body

  10. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients.

    NARCIS (Netherlands)

    Saunders, D.P.; Epstein, J.B.; Elad, S.; Allemano, J.; Bossi, P.; Wetering, M.D. van de; Rao, N.G.; Potting, C.M.J.; Cheng, K.K.; Freidank, A.; Brennan, M.T.; Bowen, J.; Dennis, K.; Lalla, R.V.

    2013-01-01

    PURPOSE: The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. METHODS: A systematic review of the available literature was

  11. Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naïve atrial fibrillation patients

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; Sørensen, Rikke; Hansen, Morten Lock

    2015-01-01

    AIMS: Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted. METHODS AND RESULTS: Using Danish nationwide administrative registers, we identif...

  12. Improved oral bioavailability in rats of SR13668, a novel anti-cancer agent.

    Science.gov (United States)

    Green, Carol E; Swezey, Robert; Bakke, James; Shinn, Walter; Furimsky, Anna; Bejugam, Naveen; Shankar, Gita N; Jong, Ling; Kapetanovic, Izet M

    2011-05-01

    SR13668, a bis-indole with potent activity in vitro and in vivo against various cancers and promising cancer chemopreventive activity, was found to have very low oral bioavailability, <1%, in rats during pilot pharmacokinetic studies. The objective of these studies was to better understand the source of low oral exposure and to develop a formulation that could be used in preclinical development studies. An automated screening system for determining solubility in lipid-based vehicles, singly and in combination, was used to identify formulations that might enhance absorption by improving solubility of SR13668, and these results were confirmed in vivo using Sprague-Dawley rats. Pharmacokinetics of SR13668 was then determined in male and female Sprague-Dawley rats administered 1 mg/kg iv, 1, 10, and 30 mg/kg po formulated in PEG400:Labrasol (1:1 v/v). Blood was collected at time points through 24 h and the concentration of SR13668 determined using HPLC with UV and fluorescence detection. SR13668 was found to be resistant to plasma esterases in vitro and relatively stable to rat and human liver microsomal metabolism. SR13668 concentrates in tissues as indicated by significantly higher levels in lung compared to blood, blood concentrations ~2.5-fold higher than plasma levels, and apparent volume of distribution (V) of ~5 l/kg. A marked sex difference was observed in exposure to SR13668 with area under the curve (AUC) significantly higher and clearance (CL) lower for female compared to male rats, after both iv and oral administration. The oral bioavailability (F) of SR13668 was 25.4 ± 3.8 and 27.7 ± 3.9% (30 mg/kg), for males and females, respectively. A putative metabolite (M1), molecular weight of 445 in the negative ion mode (i.e., SR13668 + 16), was identified in blood samples from both the iv and po routes, as well as in vitro microsomal samples. In summary, while SR13668 does undergo metabolism, probably by the liver, the oral bioavailability of SR13668 in rats

  13. Oral antineoplastic agent interactions with medicinal plants and food: an issue to take into account.

    Science.gov (United States)

    Collado-Borrell, Roberto; Escudero-Vilaplana, Vicente; Romero-Jiménez, Rosa; Iglesias-Peinado, Irene; Herranz-Alonso, Ana; Sanjurjo-Sáez, María

    2016-11-01

    To review interactions between oral antineoplastic agents (OAAs) for the treatment of solid and hematological tumors and common food and medicinal plants. All potential interactions between OAAs, medicinal plants and food were reviewed. OAAs were considered to be drugs for oral administration that have direct antitumor activity and were approved by the European Medicines Agency in April 2015. We performed the literature search in Pubmed(®) considering only medicinal plants and food. In addition, available data were analyzed from each OAA in secondary data sources taken from Thomson Micromedex(®) and Lexi-comp(®), as well as in the summary of product characteristics. Fifty-eight OAAs were analyzed. We found interactions in 60.3 % of OAAs. Those with most interactions described were: imatinib and procarbazine (4 interactions) and erlotinib, vemurafenib, pomalidomide, medroxyprogesterone and methotrexate (3 interactions). We found 39 interactions (74.4 % important). St. John's wort was the medicinal plant with most interactions (92.6 % were considered important). The rest were: important (ginseng-imatinib, methotrexate-cola and tobacco-erlotinib and tobacco-pomalidomide) and moderate (caffeine-vemurafenib/medroxyprogesterone, medroxyprogesterone-ruxolitinib/St. John's wort, garlic-anagrelide and ginseng-procarbazine). Twenty-six interactions (61.5 % important). Grapefruit had most interactions (82.4 % were considered important). The rest were: important (alcohol-procarbazine) and moderate (dairy-estramustine, methotrexate-ethanol, procarbazine-tyramine, vitamin A-tretinoin/bexarotene and grapefruit-bexarotene/etoposide/sunitinib). A review of interactions of medicinal plants and food should be taken into account in the management of OAAs, since more than half have interactions with MPs and food, of which 70.3 % are considered important. The most relevant are HSJ, grapefruit, ginseng and tobacco. This review is intended to serve as a support to all healthcare

  14. The use of anaesthetic agents to provide anxiolysis and sedation in dentistry and oral surgery.

    Science.gov (United States)

    O'Halloran, Michael

    2013-12-31

    Throughout the world there is considerable variation in the techniques used to manage anxious dental patients requiring treatment. Traditionally anxious or phobic dental patients may have been sent for general anaesthesia to allow dental treatment be undertaken. While this is still the case for the more invasive oral surgical procedures, such as wisdom teeth extraction, sedation in general dentistry is becoming more popular. Various sedation techniques using many different anaesthetic agents have gained considerable popularity over the past 30 years. While the practice of sedating patients for dental procedures is invaluable in the management of suitably assessed patients, patient safety must always be the primary concern. Medical, dental and psychosocial considerations must be taken into account when evaluating the patient need and the patient suitability for sedation or general anaesthesia. The regulations that govern the practice of dental sedation vary throughout the world, in particular regarding the techniques used and the training necessary for dental practitioners to sedate patients. It is necessary for medical and dental practitioners to be up to date on current practice to ensure standards of practice, competence and safety throughout our profession. This article, the first in a two-part series, will provide information to practitioners on the practice of sedation in dentistry, the circumstances where it may be appropriate instead of general anaesthesia and the risks involved with sedation. It will also discuss the specific training and qualifications required for dental practitioners to provide sedation. The second article in this series will outline the different techniques used to administer inhalation, oral and intravenous sedation in dentistry and will focus on specific methods that are practiced.

  15. Combined oral contraceptives versus levonorgestrel for emergency contraception.

    Science.gov (United States)

    Strayer, S M; Couchenour, R L

    1998-12-01

    A study supported by the World Health Organization's Task Force on Postovulatory Methods of Fertility Control compared the efficacy of the Yuzpe and levonorgestrel-only methods of emergency contraception (EC). Enrolled in this double-blind, randomized trial were 1998 women from 21 centers around the world who requested EC within 72 hours of unprotected intercourse. The pregnancy rate was 1.1% for levonorgestrel alone and 3.2% for the combined ethinyl estradiol-levonorgestrel regimen. The crude relative risk of pregnancy was 0.36 (95% confidence interval, 0.18-0.70) for levonorgestrel compared with the Yuzpe regimen. The former method prevented 85% of expected pregnancies, while the latter prevented only 57%. Finally, side effects such as nausea, vomiting, dizziness, and fatigue were significantly less common in the levonorgestrel group. Although these findings document the superiority of the levonorgestrel regimen for EC, the 0.75 mg tablets are not currently manufactured in the US.

  16. Efficacy of steroidal vs non-steroidal agents in oral lichen planus: a randomised, open-label study.

    Science.gov (United States)

    Singh, A R; Rai, A; Aftab, M; Jain, S; Singh, M

    2017-01-01

    This study compared the therapeutic efficacy of steroidal and non-steroidal agents for treating oral lichen planus. Forty patients with clinical and/or histologically proven oral lichen planus were randomly placed into four groups and treated with topical triamcinolone, oral dapsone, topical tacrolimus or topical retinoid for three months. Pre- and post-treatment symptoms and signs were scored for each patient. Patients in all treatment groups showed significant clinical improvement after three months (p 0.05) and for topical retinoid vs topical tacrolimus (p > 0.05). Non-steroidal drugs such as dapsone, tacrolimus and retinoid are as efficacious as steroidal drugs for treating oral lichen planus, and avoid the side effects associated with steroids.

  17. Combined therapeutic use of oral alitretinoin and narrowband ultraviolet-B therapy in the treatment of Hailey-Hailey disease

    Directory of Open Access Journals (Sweden)

    Kaitlin A. Vanderbeck

    2014-11-01

    Full Text Available Hailey-Hailey disease (HHD is a chronic familial bullous disease characterized by recurrent blisters and erosions typically at friction-prone areas of the body accompanied by acantholysis upon histologic examination. There are a number of therapies used in the management of HHD. Its symptoms have been effectively treated with antimicrobial therapies, corticosteroids and other agents such as cyclosporine and prednisone. However, such treatments are not always effective. Therefore, there is a need for new treatments for the management of HHD. In this report, a patient with long-standing HHD responsive only to high levels of prednisone is described. After the successful tapering and cessation of oral prednisone the patient began a new combination therapy of complementary doses of oral alitretinoin, and narrowband UVB therapy, which yielded a favorable response within 2-3 weeks. After 6 weeks, a mono-therapy of daily (30 mg oral alitretinoin was sufficient to maintain successful near-complete remission of the disease.

  18. Boron microquantification in oral mucosa and skin following administration of a neutron capture therapy agent

    International Nuclear Information System (INIS)

    Kiger, S.W. III; Micca, P.L.; Morris, G.M.; Coderre, J.A.

    2002-01-01

    Clinical trials of boron neutron capture therapy (BNCT) for intracranial tumours using boronphenylalanine-fructose undertaken at Harvard-MIT and Brookhaven National Laboratory have observed acute normal tissue reactions in the skin and oral mucosa. Because the range of the 10 B(n,a) 7 Li reaction products is very short, 10-14 μm combined, knowledge of the 10B microdistribution in tissue is critical for understanding the microdosimetry and radiobiology of BNCT. This paper reports measurements of the microdistribution of 10 B in an animal model, rat skin and tongue, using high resolution quantitative autoradiography (HRQAR), a neutron-induced track etch autoradiographic technique. The steep spatial gradient and high absolute value relative to blood of the 10 B concentration observed in some strata of the rat tongue epithelium and skin are important for properly evaluating the radiobiology and the biological effectiveness factors for normal tissue reactions such as oral mucositis, which are generally assessed using the blood boron concentration rather than the tissue boron concentration. (author)

  19. Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

    Science.gov (United States)

    Boria, Pedro A; Murry, Daryl J; Bennett, Peter F; Glickman, Nita W; Snyder, Paul W; Merkel, Brenna L; Schlittler, Deborah L; Mutsaers, Anthony J; Thomas, Rose M; Knapp, Deborah W

    2004-02-01

    To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. Prospective nonrandomized clinical trial. 25 dogs. Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

  20. Enhanced degradation of chitosan by applying plasma treatment in combination with oxidizing agents for potential use as an anticancer agent.

    Science.gov (United States)

    Chokradjaroen, Chayanaphat; Rujiravanit, Ratana; Watthanaphanit, Anyarat; Theeramunkong, Sewan; Saito, Nagahiro; Yamashita, Kazuko; Arakawa, Ryuichi

    2017-07-01

    Solution plasma (SP) treatment in combination with oxidizing agents, i.e., hydrogen peroxide (H 2 O 2 ), potassium persulfate (K 2 S 2 O 8 ) and sodium nitrite (NaNO 2 ) were adopted to chitosan degradation in order to achieve fast degradation rate, low chemicals used and high yield of low-molecular-weight chitosan and chitooligosaccharide (COS). Among the studied oxidizing agents, H 2 O 2 was found to be the best choice in terms of appreciable molecular weight reduction without major change in chemical structure of the degraded products of chitosan. By the combination with SP treatment, dilute solution of H 2 O 2 (4-60mM) was required for effective degradation of chitosan. The combination of SP treatment and dilute solution of H 2 O 2 (60mM) resulted in the great reduction of molecular weight of chitosan and water-soluble chitosan was obtained as a major product. The resulting water-soluble chitosan was precipitated to obtain COS. An inhibitory effect against cervical cancer cell line (HeLa cells) of COS was also examined. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

    Science.gov (United States)

    Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

    2003-07-15

    Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

  2. Searching for an alternative oral contrast agent for GI tract MR imaging; in vitro phase, initial report

    International Nuclear Information System (INIS)

    Okla, W.; Szeszkowski, W.; Cieszanowski, A.; Golebiowski, M.

    2002-01-01

    MR has been recently considered to be suitable method for detection GI tract pathologies. A few substances (some of a natural origin) seem to act as an efficient oral MR contrast agents. The aim of this study is to find an alternative substance, which can be administrated orally to patients in order to enhance signal intensity (SI). The ideal agent should have a biphase pattern (high SI in T1 and low in T2), and should be nontoxic and cost effective. Phantom experiments were conducted with 1.5 T MR scanner. T1W and T2W sequences were used for initial estimation. Number of different agents such as: water, Gd-DTPA, barium sulfate, green tea, blueberry juice, cranberry juice, blackcurrant juice, and some more were evaluated. Signal intensity was measured by using elliptical region of interest (ROI). MR imaging in one patient with stomach cancer was also performed. In T1W-FFE sequence cranberry juice reached satisfactorily high signal (SI=1760.14). In T2W-TSE sequence this substance reduced signal intensity (SI=23.10) almost to background level. Blueberry juice appear to be the next substance capable to generate high signal (SI=1558.31) in T1W sequence (T1-TSE). MR examination of a patient with stomach adenocarcinoma (using blueberry juice as an oral contrast agent) satisfactorily depicted and delineated tumor mass on both: T1W and T2W images. Cranberry juice and blueberry juice seemed to act effectively as oral contrast agents for gastrointestinal MR imaging. Thus they need further exploration and trials. (author)

  3. Combined Oral Contraceptive Pills: Profile of Acceptors in a Tertiary Hospital in South-South Nigeria.

    Science.gov (United States)

    Abasiattai, A M; Utuk, M N; Ojeh, S O; Eyo, U E

    2011-01-01

    BACKGROUND: Combined oral contraceptive pills were the first contraceptive method to provide sexual freedom of choice for women through reliable, personal and private control of fertility. They are the most widely used hormonal contraceptives and also the most popular non-surgical method of contraception. OBJECTIVE: To review the profile of acceptors of combined oral contraceptive pills at the University of Uyo Teaching Hospital, Uyo. METHODOLOGY: An 8 year review of all clients that accepted combined oral contraceptive pills in the family planning clinic. RESULTS: There were 1,146 new contraceptive acceptors during the period of study out of which 309 (27.9%) accepted the pills. Majority of the clients were between 20 and 29 years of age (54.0%), were multiparous (72.8%), Christians (99.7%) and 61.2% had tertiary level education. Two hundred and fifty-five women (82.5%) desired to use combined oral contraceptive pills to space births while 7.8% wanted to limit child bearing. There was a high discontinuation rate among the women (45.0%) and out of these 87.9% of the clients changed to other contraceptive methods. All the clients commenced their pills within seven days of menstruation and only the low dose monophasic preparations were available in the family planning unit and thus were given to the clients. CONCLUSION: Women who accept to initiate combined oral contraceptive pills in our center are young, well educated, multiparous women who want to space their pregnancies. However, due to the high discontinuation rate among the clients, there is need for further studies evaluating reasons for the high discontinuation rate, exploring interactions between clients and providers' and also providers' attitude towards combined pills in our environment.

  4. Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

    Science.gov (United States)

    Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

    2014-03-01

    There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

  5. Combined compared to dissociated oral and intestinal sucrose stimuli induce different brain hedonic processes

    Directory of Open Access Journals (Sweden)

    Caroline eClouard

    2014-08-01

    Full Text Available The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggered by oral and/or intestinal sucrose sensing in pigs. Seven animals underwent brain single photon emission computed tomography (99mTc-HMPAO further to oral stimulation with neutral or sucrose artificial saliva paired with saline or sucrose infusion in the duodenum, the proximal part of the intestine. Oral and/or duodenal sucrose sensing induced differential cerebral blood flow (CBF changes in brain regions known to be involved in memory, reward processes and hedonic (i.e. pleasure evaluation of sensory stimuli, including the dorsal striatum, prefrontal cortex, cingulate cortex, insular cortex, hippocampus and parahippocampal cortex. Sucrose duodenal infusion only and combined sucrose stimulation induced similar activity patterns in the putamen, ventral anterior cingulate cortex and hippocampus. Some brain deactivations in the prefrontal and insular cortices were only detected in the presence of oral sucrose stimulation. Finally, activation of the right insular cortex was only induced by combined oral and duodenal sucrose stimulation, while specific activity patterns were detected in the hippocampus and parahippocampal cortex with oral sucrose dissociated from caloric load. This study sheds new light on the brain hedonic responses to sugar and has potential implications to unravel the neuropsychological mechanisms underlying food pleasure and motivation.

  6. The role of combined oral contraceptives in the management of acne and seborrhea.

    Science.gov (United States)

    del Marmol, V; Teichmann, A; Gertsen, K

    2004-06-01

    Acne and seborrhea (or facial oiliness) are related androgenic skin disorders which affect a high proportion of women after menarche. They can have a negative effect on psychological well-being and social life. Androgens play an important role in the pathogenesis of acne through the stimulation of sebum secretion, increasing sebaceous gland size and possibly through follicular hyperkeratinization. Conversely, estrogens decrease sebum production by suppressing gonadotropin release and androgen production and increasing sex hormone binding globulin production. One of the treatment options for these conditions is hormonal therapy, especially for women who require contraception. The effect of combined oral contraceptives in androgenic skin disorders depends on their estrogen:progestogen balance and on the antiestrogenic activity of the progestogen component. Improved understanding of what women value about oral contraceptives suggests that the choice of product should be tailored as much as possible to the individual. Several combined oral contraceptives containing new-generation progestogens (e.g. desogestrel, gestodene) or progestational antiandrogens (e.g. cyproterone acetate, chlormadinone acetate) have demonstrated efficacy in the treatment of women with acne, although comparisons between trials are difficult because of differing endpoints. Seborrhea has been less well studied, but the few studies that are available show an improvement in women with this condition using combined oral contraceptives.

  7. Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent.

    Science.gov (United States)

    Qi, Xiaole; Chen, Haiyan; Rui, Yao; Yang, Fengjiao; Ma, Ning; Wu, Zhenghong

    2015-07-15

    To prolong the residence time of dosage forms within gastrointestinal trace until all drug released at desired rate was one of the real challenges for oral controlled-release drug delivery system. Herein, we developed a fine floating tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) to achieve simultaneous control of release rate and location of ofloxacin. Sodium alginate was also added in the coating layer to regulate the drug release rate. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated. The optimized formulations were found to immediately float within 30s and remain lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2) without pepsin, indicating a satisfactory floating and zero-order drug release profile. In addition, the oral bioavailability experiment in New Zealand rabbits showed that, the relative bioavailability of the ofloxacin after administrated of floating tablets was 172.19%, compared to marketed common release tablets TaiLiBiTuo(®). These results demonstrated that those controlled-released floating tables would be a promising gastro-retentive delivery system for drugs acting in stomach. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The combination of novel targeted molecular agents and radiation in the treatment of pediatric gliomas

    Directory of Open Access Journals (Sweden)

    Tina eDasgupta

    2013-05-01

    Full Text Available Brain tumors are the most common solid pediatric malignancy. For high-grade, recurrent or refractory pediatric brain tumors, radiation therapy (XRT is an integral treatment modality. In the era of personalized cancer therapy, molecularly targeted agents have been designed to inhibit pathways critical to tumorigenesis. Our evolving knowledge of genetic aberrations in low-grade gliomas is being exploited with targeted inhibitors. These agents are also being combined with XRT to increase their efficacy. In this review, we discuss novel agents targeting three different pathways in low-grade gliomas, and their potential combination with XRT. B-Raf is a kinase in the Ras/Raf/MAPK kinase pathway, which is integral to cellular division, survival and metabolism. In low-grade pediatric gliomas, point mutations in BRAF (BRAF V600E or a BRAF fusion mutation (KIAA1549:BRAF causes overactivation of the MEK/MAPK pathway. Pre-clinical data shows cooperation between XRT and tagrgeted inhibitors of BRAF V600E, and MEK and mTOR inhibitors in the gliomas with the BRAF fusion. A second important signaling cascade in pediatric glioma pathogenesis is the PI3 kinase (PI3K/mTOR pathway. Dual PI3K/mTOR inhibitors are poised to enter studies of pediatric tumors. Finally, many brain tumors express potent stimulators of angiogenesis. Several inhibitors of immunomodulators are currently being evaluated in in clinical trials for the treatment of recurrent or refractory pediatric central nervous system (CNS tumors. In summary, combinations of these targeted inhibitors with radiation are currently under investigation in both translational bench research and early clinical trials. We summarize the molecular rationale for, and the pre-clinical data supporting the combinations of these targeted agents with other anti-cancer agents and XRT in pediatric gliomas. Parallels are drawn to adult gliomas, and the molecular mechanisms underlying the efficacy of these agents is discussed

  9. Physical and chemical stability of proflavine contrast agent solutions for early detection of oral cancer.

    Science.gov (United States)

    Kawedia, Jitesh D; Zhang, Yan-Ping; Myers, Alan L; Richards-Kortum, Rebecca R; Kramer, Mark A; Gillenwater, Ann M; Culotta, Kirk S

    2016-02-01

    Proflavine hemisulfate solution is a fluorescence contrast agent to visualize cell nuclei using high-resolution optical imaging devices such as the high-resolution microendoscope. These devices provide real-time imaging to distinguish between normal versus neoplastic tissue. These images could be helpful for early screening of oral cancer and its precursors and to determine accurate margins of malignant tissue for ablative surgery. Extemporaneous preparation of proflavine solution for these diagnostic procedures requires preparation in batches and long-term storage to improve compounding efficiency in the pharmacy. However, there is a paucity of long-term stability data for proflavine contrast solutions. The physical and chemical stability of 0.01% (10 mg/100 ml) proflavine hemisulfate solutions prepared in sterile water was determined following storage at refrigeration (4-8℃) and room temperature (23℃). Concentrations of proflavine were measured at predetermined time points up to 12 months using a validated stability-indicating high-performance liquid chromatography method. Proflavine solutions stored under refrigeration were physically and chemically stable for at least 12 months with concentrations ranging from 95% to 105% compared to initial concentration. However, in solutions stored at room temperature increased turbidity and particulates were observed in some of the tested vials at 9 months and 12 months with peak particle count reaching 17-fold increase compared to baseline. Solutions stored at room temperature were chemically stable up to six months (94-105%). Proflavine solutions at concentration of 0.01% were chemically and physically stable for at least 12 months under refrigeration. The solution was chemically stable for six months when stored at room temperature. We recommend long-term storage of proflavine solutions under refrigeration prior to diagnostic procedure. © The Author(s) 2014.

  10. Comparison of 3% sorbitol vs psyllium fibre as oral contrast agents in MR enterography.

    Science.gov (United States)

    Saini, Sidharth; Colak, Errol; Anthwal, Shalini; Vlachou, Paraskevi A; Raikhlin, Antony; Kirpalani, Anish

    2014-10-01

    To compare the degree of small bowel distension achieved by 3% sorbitol, a high osmolarity solution, and a psyllium-based bulk fibre as oral contrast agents (OCAs) in MR enterography (MRE). This retrospective study was approved by our institutional review board. A total of 45 consecutive normal MRE examinations (sorbitol, n = 20; psyllium, n = 25) were reviewed. The patients received either 1.5 l of 3% sorbitol or 2 l of 1.6 g kg(-1) psyllium prior to imaging. Quantitative small bowel distension measurements were taken in five segments: proximal jejunum, distal jejunum, proximal ileum, distal ileum and terminal ileum by two independent radiologists. Distension in these five segments was also qualitatively graded from 0 (very poor) to 4 (excellent) by two additional independent radiologists. Statistical analysis comparing the groups and assessing agreement included intraclass coefficients, Student's t-test and Mann-Whitney U-test. Small bowel distension was not significantly different in any of the five small bowel segments between the use of sorbitol and psyllium as OCAs in both the qualitative (p = 0.338-0.908) and quantitative assessments (p = 0.083-0.856). The mean bowel distension achieved was 20.1 ± 2.2 mm for sorbitol and 19.8 ± 2.5 mm for psyllium (p = 0.722). Visualization of the ileum was good or excellent in 65% of the examinations in both groups. Sorbitol and psyllium are not significantly different at distending the small bowel and both may be used as OCAs for MRE studies. This is the first study to directly compare the degree of distension in MRE between these two common, readily available and inexpensive OCAs.

  11. Combined blood pool and extracellular contrast agents for pediatric and young adult cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Joyce T. [Ann and Robert Lurie Children' s Hospital of Chicago, Division of Pediatric Cardiology, 225 E. Chicago Ave., Box 21, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Robinson, Joshua D. [Ann and Robert Lurie Children' s Hospital of Chicago, Division of Pediatric Cardiology, 225 E. Chicago Ave., Box 21, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Deng, Jie [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Rigsby, Cynthia K. [Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2016-12-15

    A comprehensive cardiac magnetic resonance (cardiac MR) study including both late gadolinium enhancement (LGE) and MR angiography may be indicated for patients with a history of acquired or congenital heart disease. To study the novel use of an extracellular agent for assessment of LGE combined with a blood pool contrast agent for detailed MR angiography evaluation to yield a comprehensive cardiac MR study in these patients. We reviewed clinical cardiac MR studies utilizing extracellular and blood pool contrast agents and noted demographics, clinical data and adverse events. We rated LGE image quality and MR angiography image quality for each vascular segment and calculated inter-rater variability. We also quantified contrast-to-noise ratio (CNR). Thirty-three patients (mean age 13.9 ± 3 years) received an extracellular contrast agent (10 gadobenate dimeglumine, 23 gadopentetate dimeglumine) and blood pool contrast agent (33 gadofosveset trisodium). No adverse events were reported. MRI indications included Kawasaki disease (8), cardiomyopathy and coronary anatomy (15), repaired congenital heart disease (8), and other (2). Mean LGE quality was 2.6 ± 0.6 with 97% diagnostic imaging. LGE quality did not vary by type of contrast agent given (P = 0.07). Mean MR angiography quality score was 4.7 ± 0.6, with high inter-rater agreement (k = 0.6-0.8, P < 0.002). MR angiography quality did not vary by type of contrast agent used (P = 0.6). Cardiac MR studies utilizing both extracellular and blood pool contrast agents are feasible and safe and provide excellent-quality LGE and MR angiography images. The use of two contrast agents allows for a comprehensive assessment of both myocardial viability and vascular anatomy during the same exam. (orig.)

  12. Combined blood pool and extracellular contrast agents for pediatric and young adult cardiovascular magnetic resonance imaging

    International Nuclear Information System (INIS)

    Johnson, Joyce T.; Robinson, Joshua D.; Deng, Jie; Rigsby, Cynthia K.

    2016-01-01

    A comprehensive cardiac magnetic resonance (cardiac MR) study including both late gadolinium enhancement (LGE) and MR angiography may be indicated for patients with a history of acquired or congenital heart disease. To study the novel use of an extracellular agent for assessment of LGE combined with a blood pool contrast agent for detailed MR angiography evaluation to yield a comprehensive cardiac MR study in these patients. We reviewed clinical cardiac MR studies utilizing extracellular and blood pool contrast agents and noted demographics, clinical data and adverse events. We rated LGE image quality and MR angiography image quality for each vascular segment and calculated inter-rater variability. We also quantified contrast-to-noise ratio (CNR). Thirty-three patients (mean age 13.9 ± 3 years) received an extracellular contrast agent (10 gadobenate dimeglumine, 23 gadopentetate dimeglumine) and blood pool contrast agent (33 gadofosveset trisodium). No adverse events were reported. MRI indications included Kawasaki disease (8), cardiomyopathy and coronary anatomy (15), repaired congenital heart disease (8), and other (2). Mean LGE quality was 2.6 ± 0.6 with 97% diagnostic imaging. LGE quality did not vary by type of contrast agent given (P = 0.07). Mean MR angiography quality score was 4.7 ± 0.6, with high inter-rater agreement (k = 0.6-0.8, P < 0.002). MR angiography quality did not vary by type of contrast agent used (P = 0.6). Cardiac MR studies utilizing both extracellular and blood pool contrast agents are feasible and safe and provide excellent-quality LGE and MR angiography images. The use of two contrast agents allows for a comprehensive assessment of both myocardial viability and vascular anatomy during the same exam. (orig.)

  13. The combined use of radiotherapy and immunochemotherapy with Krestin for intra-oral cancer

    International Nuclear Information System (INIS)

    Komatsu, Yukihisa; Kuroda, Manabu

    1981-01-01

    Interstitial irradiation with needles 226 Ra was performed on 3 patients with intra-oral cancer. Krestin, an immunotherapeutic agent, was administered three times a day. All patients were also given 600 mg of FT-207/day as adjuvant chemotherapy. Moreover, one of them was also given 0.75 mg/day of eskinon every day. As parameters of immunological competence, PPD and PHA intracutaneous responses and the lymphocyte count in peripheral blood were used. Ulcers of intra-oral cancer were completely heated and there was no lymph node enargement. Though there were changes in PPD intracutaneous responses among three patients, positive responses were maintained. Absolute values of the lymphocyte count in peripheral blood were almost above 1,000/mm 3 in patients treated with both krestin and FT-207, but those in a patient treated with additional eskinon decreased gradually to 450/mm 3 . (Tsunoda, M.)

  14. A new manganese-based oral contrast agent (CMC-001) for liver MRI. Pharmacological and pharmaceutical aspects

    International Nuclear Information System (INIS)

    Joergensen, Jan Troest; Rief, Matthias; Wagner, Moritz; Brismar, Torkel B.; Albiin, Nils

    2012-01-01

    Manganese is one of the most abundant metals on earth and is found as a component of more than 100 different minerals. Besides being an essential trace element in relation to the metabolic processes in the body, manganese is also a paramagnetic metal that possesses similar characteristics to gadolinium with regards to T1-weighted (T1-w) magnetic resonance imaging (MRI). Manganese, in the form of manganese (II) chloride tetrahydrate, is the active substance in a new targeted oral contrast agent, currently known as CMC-001, indicated for hepatobiliary MRI. Under physiological circumstances manganese is poorly absorbed from the intestine after oral intake, but by the use of specific absorption promoters, L-alanine and vitamin D3, it is possible to obtain a sufficiently high concentration in the liver in order to achieve a significant signal enhancing effect. In the liver manganese is exposed to a very high first-pass effect, up to 98 %, which prevents the metal from reaching the systemic circulation, thereby reducing the number of systemic side-effects. Manganese is one of the least toxic trace elements, and due to its favorable safety profile it may be an attractive alternative to gadolinium-based contrast agents for patients undergoing an MRI evaluation for liver metastases in the future. In this review the basic pharmacological and pharmaceutical aspects of this new targeted oral hepatobiliary specific contrast agent will be discussed

  15. Comparison of oral midazolam with a combination of oral midazolam and nitrous oxide-oxygen inhalation in the effectiveness of dental sedation for young children

    Directory of Open Access Journals (Sweden)

    Al-Zahrani A

    2009-03-01

    Full Text Available Aim: To compare the effectiveness of 0.6 mg/kg oral midazolam sedation alone and a combination of 0.6 mg/kg oral midazolam plus nitrous oxide-oxygen inhalation sedation, in controlling the behavior of uncooperative children during dental treatment. Study Design: The study had a crossover design where the same patient received two different sedation regimens, that is, oral midazolam 0.6 mg/kg and oral midazolam 0.6 mg/kg with nitrous oxide-oxygen inhalation during two dental treatment visits. Materials and Methods: Thirty children (17 males and 13 females were randomly selected for the study, with a mean age of 55.07 (± 9.29 months, ranging from 48 - 72 months. A scoring system suggested by Houpt et al. (1985 was utilized for assessment of the children′s behavior. Results : There was no significant (p > 0.05 difference in the overall behavior assessment between the two sedation regimens, that is, oral midazolam alone and oral midazolam plus nitrous oxide-oxygen. However, the combination of midazolam and nitrous oxide-oxygen showed significantly (p < 0.05 superior results as compared to midazolam alone, in terms of controlling movement and crying during local anesthesia administration and restorative procedures. Conclusion: Compared to oral midazolam alone, a combination of oral midazolam and nitrous oxide inhalation sedation appears to provide more comfort to pediatric dental patients and operators during critical stages of dental treatment.

  16. The In Vitro Antimicrobial Effects of Lavandula angustifolia Essential Oil in Combination with Conventional Antimicrobial Agents

    Science.gov (United States)

    de Rapper, Stephanie; Viljoen, Alvaro

    2016-01-01

    The paper focuses on the in vitro antimicrobial activity of Lavandula angustifolia Mill. (lavender) essential oil in combination with four commercial antimicrobial agents. Stock solutions of chloramphenicol, ciprofloxacin, nystatin, and fusidic acid were tested in combination with L. angustifolia essential oil. The antimicrobial activities of the combinations were investigated against the Gram-positive bacterial strain Staphylococcus aureus (ATCC 6538) and Gram-negative Pseudomonas aeruginosa (ATCC 27858) and Candida albicans (ATCC 10231) was selected to represent the yeasts. The antimicrobial effect was performed using the minimum inhibitory concentration (MIC) microdilution assay. Isobolograms were constructed for varying ratios. The most prominent interaction was noted when L. angustifolia essential oil was combined with chloramphenicol and tested against the pathogen P. aeruginosa (ΣFIC of 0.29). Lavendula angustifolia essential oil was shown in most cases to interact synergistically with conventional antimicrobials when combined in ratios where higher volumes of L. angustifolia essential oil were incorporated into the combination. PMID:27891157

  17. The In Vitro Antimicrobial Effects of Lavandula angustifolia Essential Oil in Combination with Conventional Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Stephanie de Rapper

    2016-01-01

    Full Text Available The paper focuses on the in vitro antimicrobial activity of Lavandula angustifolia Mill. (lavender essential oil in combination with four commercial antimicrobial agents. Stock solutions of chloramphenicol, ciprofloxacin, nystatin, and fusidic acid were tested in combination with L. angustifolia essential oil. The antimicrobial activities of the combinations were investigated against the Gram-positive bacterial strain Staphylococcus aureus (ATCC 6538 and Gram-negative Pseudomonas aeruginosa (ATCC 27858 and Candida albicans (ATCC 10231 was selected to represent the yeasts. The antimicrobial effect was performed using the minimum inhibitory concentration (MIC microdilution assay. Isobolograms were constructed for varying ratios. The most prominent interaction was noted when L. angustifolia essential oil was combined with chloramphenicol and tested against the pathogen P. aeruginosa (ΣFIC of 0.29. Lavendula angustifolia essential oil was shown in most cases to interact synergistically with conventional antimicrobials when combined in ratios where higher volumes of L. angustifolia essential oil were incorporated into the combination.

  18. A combination of biocontrol agents improves the management of dry root rot (Macrophomina phaseolina in greengram

    Directory of Open Access Journals (Sweden)

    R. Thilagavathi

    2007-08-01

    Full Text Available The biocontrol agents Trichoderma viride (strains Tv1 and Tv13, Pseudomonas fluorescens (Pf1 and Py15 and Bacillus subtilis (Bs16 were tested individually and in combination for their effectiveness against root rot of greengram caused by Macrophomina phaseolina. As regards the compatibility of the biocontrol agents with each other, T. viride strains were not compatible with B. subtilis (Bs16, but P. fluorescens strains were compatible with B. subtilis and T. viride. Of the biocontrol agents tested in vitro against M. phaseolina, combinations of P. fluorescens+T. viride (Pf1+Tv1, Pf1+Tv13 and Py15+Tv1 inhibited mycelial growth of the pathogen and they also promoted the growth of the greengram seedlings. A combination of Pf1+Tv1 was most effective in reducing root rot incidence under glass-house and field conditions as compared with other single or combined treatments or the untreated control. The activity of the defense-related enzymes peroxidase, polyphenol oxidase and phenyl alanine ammonia lyase was significantly greater in greengram plants treated with a talc based formulation containing Pf1+Tv1 followed by Pf1+Tv13 and Py15+Tv1, than in plants receiving other treatments or the untreated control. Moreover, a combination of Pf1+Tv1 followed by Pf1+Tv13 and Py15+Tv1 significantly increased yield under glass house and field conditions.

  19. DNA repair in mammalian cells exposed to combinations of carcinogenic agents

    International Nuclear Information System (INIS)

    Setlow, R.B.; Ahmed, F.E.

    1979-01-01

    Cells defective in one or more aspects of repair are killed and often mutagenized more readily than normal cells by DNA damaging agents, and humans whose cells are deficient in repair are at an increased carcinogenic risk compared to normal individuals. The excision repair of uv induced pyrimidine dimers is a well studied system, but the details of the steps in this repair system are far from being understood in human cells. We know that there are a number of chemicals that mimic uv in that normal human cells repair DNA damage from both these agents and from uv by a long patch excision repair system, and that xeroderma pigmentosum cells defective in repair of uv are also defective in the repair of damage from these chemicals. The chemicals we have investigated are AAAF, 4-NQO, DMBA-epoxide, and ICR-170. We describe experiments, using several techniques, in which DNA excision repair is measured after treatment of various human cell strains with combinations of uv and these agents. If two agents have a common rate limiting step then, at doses high enough to saturate the repair system, one would expect the observed repair after a treatment with a combination of agents to be equal to that from one agent alone. Such is not the case for normal human or excision-deficient XP cells. In the former repair is additive and in the latter repair is usually appreciably less than that observed with either agent alone. Models that attempt to explain these surprising results involve complexes of enzymes and cofactors

  20. Combined effect of environmental radiation and other agents: Is there a synergism trap?

    International Nuclear Information System (INIS)

    Hornhardt, S.; Jung, T.; Burkart, W.

    2002-01-01

    Most assessments of possible deleterious outcomes from environmental and occupational exposures concentrate on single agents and neglect the potential for combined effects, i.e. synergisms or antagonisms. Biomechanistic considerations based on multistep processes such as carcinogenesis indicate the potential for highly detrimental interactions, if two or more consecutive rate limiting steps are specifically effected by different agents. However, low specificity towards molecular structure or DNA-sequence - and therefore exchangeability - of many genotoxic agents indicate little functional specificity and therefore little vulnerability towards synergism at most occupational and environmental exposure situations. The low potential for significant combined effects for those common low exposure situations where non-genotoxic agents with highly non-linear dose effect relationships and apparent thresholds are involved, is also evident. Nevertheless, a quantitative assessment of the contribution of synergistic interactions to the total detriment from natural and man-made toxicants based on experimental data is far away. The existing database on combined effects is rudimentary, mainly descriptive and rarely covers exposure ranges large enough to make direct inferences to present day low dose exposure situations. In view of the multitude of possible interactions between the large number of potentially harmful agents in the human environment, descriptive approaches will have to be supplemented by the use of mechanistic models for critical health endpoints such as cancer. Finally an important question considering the shape of dose effect relationships for ionizing radiation arises from the unresolved question whether real or apparent thresholds may be used for any genotoxic agent separately or only one time for an exposed genome. (author)

  1. Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

    Directory of Open Access Journals (Sweden)

    Ying-Yu Kuo

    2015-05-01

    Full Text Available Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC. The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs, epidermal growth factor receptor (EGFR, and Cyclooxygenase-2 (COX-2. Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K/protein kinase B (Akt signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients.

  2. Quantitative Analysis of Intra Urban Growth Modeling using socio economic agents by combining cellular automata model with agent based model

    Science.gov (United States)

    Singh, V. K.; Jha, A. K.; Gupta, K.; Srivastav, S. K.

    2017-12-01

    Recent studies indicate that there is a significant improvement in the urban land use dynamics through modeling at finer spatial resolutions. Geo-computational models such as cellular automata and agent based model have given evident proof regarding the quantification of the urban growth pattern with urban boundary. In recent studies, socio- economic factors such as demography, education rate, household density, parcel price of the current year, distance to road, school, hospital, commercial centers and police station are considered to the major factors influencing the Land Use Land Cover (LULC) pattern of the city. These factors have unidirectional approach to land use pattern which makes it difficult to analyze the spatial aspects of model results both quantitatively and qualitatively. In this study, cellular automata model is combined with generic model known as Agent Based Model to evaluate the impact of socio economic factors on land use pattern. For this purpose, Dehradun an Indian city is selected as a case study. Socio economic factors were collected from field survey, Census of India, Directorate of economic census, Uttarakhand, India. A 3X3 simulating window is used to consider the impact on LULC. Cellular automata model results are examined for the identification of hot spot areas within the urban area and agent based model will be using logistic based regression approach where it will identify the correlation between each factor on LULC and classify the available area into low density, medium density, high density residential or commercial area. In the modeling phase, transition rule, neighborhood effect, cell change factors are used to improve the representation of built-up classes. Significant improvement is observed in the built-up classes from 84 % to 89 %. However after incorporating agent based model with cellular automata model the accuracy improved from 89 % to 94 % in 3 classes of urban i.e. low density, medium density and commercial classes

  3. Newer Clinical Strategies for Combining Interferon and Cytotoxic Agents Against Solid Tumours and Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Scott Wadler

    1994-01-01

    Full Text Available The role of interferons in the treatment of cancer continues to evolve. Despite limited single agent activity against solid tumours, interferons now appear to have an important role as modulators of the activity of a variety of cytotoxic drugs. Clinical benefits have been observed for combinations of interferons and alkylating agents against low grade lymphomas, interferons and dacarbazine against malignant melanoma, and interferons and 5-fluorouracil against gastrointestinal and genitourinary malignancies. Further progress will depend on a grealer understanding of the biology of the interaction.

  4. ZnO and TiO{sub 2} nanoparticles as novel antimicrobial agents for oral hygiene: a review

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Shams Tabrez, E-mail: shamsalig75@gmail.com; Al-Khedhairy, Abdulaziz A. [King Saud University, Department of Zoology, College of Science (Saudi Arabia); Musarrat, Javed [AMU, Department of Agricultural Microbiology, Faculty of Agricultural Sciences (India)

    2015-06-15

    Oral cavity is inhabited by more than 25,000 different bacterial phylotypes; some of them cause systemic infections in addition to dental and periodontal diseases. Emergence of multiple antibiotic resistance among these bacteria necessitates the development of alternative antimicrobial agents that are safe, stable, and relatively economic. This review focuses on the significance of metal oxide nanoparticles, especially zinc oxide and titanium dioxide nanoparticles as supplementary antimicrobials for controlling oral infections and biofilm formation. Indeed, the ZnO NPs and TiO{sub 2} NPs have exhibited significant antimicrobial activity against oral bacteria at concentrations which is not toxic in in vivo toxicity assays. These nanoparticles are being produced at an industrial scale for use in a variety of commercial products including food products. Thus, the application of ZnO and TiO{sub 2} NPs as nanoantibiotics for the development of mouthwashes, dental pastes, and other oral hygiene materials is envisaged. It is also suggested that these NPs could serve as healthier, innocuous, and effective alternative for controlling both the dental biofilms and oral planktonic bacteria with lesser side effects and antibiotic resistance.

  5. ZnO and TiO2 nanoparticles as novel antimicrobial agents for oral hygiene: a review

    Science.gov (United States)

    Khan, Shams Tabrez; Al-Khedhairy, Abdulaziz A.; Musarrat, Javed

    2015-06-01

    Oral cavity is inhabited by more than 25,000 different bacterial phylotypes; some of them cause systemic infections in addition to dental and periodontal diseases. Emergence of multiple antibiotic resistance among these bacteria necessitates the development of alternative antimicrobial agents that are safe, stable, and relatively economic. This review focuses on the significance of metal oxide nanoparticles, especially zinc oxide and titanium dioxide nanoparticles as supplementary antimicrobials for controlling oral infections and biofilm formation. Indeed, the ZnO NPs and TiO2 NPs have exhibited significant antimicrobial activity against oral bacteria at concentrations which is not toxic in in vivo toxicity assays. These nanoparticles are being produced at an industrial scale for use in a variety of commercial products including food products. Thus, the application of ZnO and TiO2 NPs as nanoantibiotics for the development of mouthwashes, dental pastes, and other oral hygiene materials is envisaged. It is also suggested that these NPs could serve as healthier, innocuous, and effective alternative for controlling both the dental biofilms and oral planktonic bacteria with lesser side effects and antibiotic resistance.

  6. ZnO and TiO2 nanoparticles as novel antimicrobial agents for oral hygiene: a review

    International Nuclear Information System (INIS)

    Khan, Shams Tabrez; Al-Khedhairy, Abdulaziz A.; Musarrat, Javed

    2015-01-01

    Oral cavity is inhabited by more than 25,000 different bacterial phylotypes; some of them cause systemic infections in addition to dental and periodontal diseases. Emergence of multiple antibiotic resistance among these bacteria necessitates the development of alternative antimicrobial agents that are safe, stable, and relatively economic. This review focuses on the significance of metal oxide nanoparticles, especially zinc oxide and titanium dioxide nanoparticles as supplementary antimicrobials for controlling oral infections and biofilm formation. Indeed, the ZnO NPs and TiO 2 NPs have exhibited significant antimicrobial activity against oral bacteria at concentrations which is not toxic in in vivo toxicity assays. These nanoparticles are being produced at an industrial scale for use in a variety of commercial products including food products. Thus, the application of ZnO and TiO 2 NPs as nanoantibiotics for the development of mouthwashes, dental pastes, and other oral hygiene materials is envisaged. It is also suggested that these NPs could serve as healthier, innocuous, and effective alternative for controlling both the dental biofilms and oral planktonic bacteria with lesser side effects and antibiotic resistance

  7. Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

    Science.gov (United States)

    Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

    2008-12-01

    Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

  8. Combined radiation therapy and intraarterial chemotherapy for advanced oral or oropharngeal carcinoma

    International Nuclear Information System (INIS)

    Okawa, Tomohiko; Kita, Midori; Tanaka, Makiko; Ishii, Tetsuo

    1989-01-01

    During the period 1982-1988, 34 patients with advanced oral or oropharyngeal carcinoma were treated with radical radiation therapy combined with intraarterial chemotherapy. Five patients were clinically staged as Stage II,15 as Stage III, and 14 as Stage IV. For intraarterial chemotherapy, ACNU (25mg/body) or CDDP (20 mg/m 2 ) plus MMC (6 mg/m 2 ) was used. Overall, the complete response rate was 56%: it was independent of the site of carcinoma, clinical stage, and the kind of drugs. The two-year cumulative survival rate was 80% for Stage II, 56% for Stage III, and 61% for Stage IV. Side effects were not so severe as to continue with the withdrawal of chemotherapy. In view of the efficacy and safety, combined radiation therapy and intraarterial chemotherapy should be performed in the treatment of oral or oropharyngeal carcinoma. (N.K.)

  9. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

    Science.gov (United States)

    Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

    2011-11-01

    The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

  10. [Effect of short-acting combined oral contraceptives on bleeding after induced abortion].

    Science.gov (United States)

    Wang, X F; Zhong, M; Liu, J

    2017-11-07

    Objective: To explore the effect of short-acting combined oral contraceptives on vaginal bleeding after induced abortion. Methods: A total of 726 patients, who had took induced abortion from July 2016 to September 2016 in obstetrics and gynecology outpatient department of Nanfang Hospital, Southern Medical University, were included and divided into the observation group and the control group according to whether they took short-acting combined oral contraceptives after induced abortion, with 312 cases, 414 cases respectively.The vaginal bleeding days, amounts of bleeding, the endometrial thickness 3 weeks later, and whether the patient had menstrual recovery on time were observed and analyzed. Results: The observation group had less bleeding days and amount of bleeding, compared with the control group.69.87% (218/312) patients of the observation group had more than 8mm of endometrial thickness on postoperative day 21, while 61.11% (253/414) of the observation group did, the difference was statistically significant ( P =0.034).90.06% (281/312) patients of the observation group had menstrual recovery on time, while 82.61% (342/414) of the observation group did, the difference was statistically significant ( P =0.004). Conclusion: Short-acting combined oral contraceptives after induced abortion can significantly shorten the vaginal bleeding days, reduce the amount of bleeding, promote endometrial repair and menstrual recovery.There fore, it has important clinical significance and application value.

  11. Modern dose-finding designs for cancer phase I trials drug combinations and molecularly targeted agents

    CERN Document Server

    Hirakawa, Akihiro; Daimon, Takashi; Matsui, Shigeyuki

    2018-01-01

    This book deals with advanced methods for adaptive phase I dose-finding clinical trials for combination of two agents and molecularly targeted agents (MTAs) in oncology. It provides not only methodological aspects of the dose-finding methods, but also software implementations and practical considerations in applying these complex methods to real cancer clinical trials. Thus, the book aims to furnish researchers in biostatistics and statistical science with a good summary of recent developments of adaptive dose-finding methods as well as providing practitioners in biostatistics and clinical investigators with advanced materials for designing, conducting, monitoring, and analyzing adaptive dose-finding trials. The topics in the book are mainly related to cancer clinical trials, but many of those topics are potentially applicable or can be extended to trials for other diseases. The focus is mainly on model-based dose-finding methods for two kinds of phase I trials. One is clinical trials with combinations of tw...

  12. Estimate of Venous Thromboembolism and Related-Deaths Attributable to the Use of Combined Oral Contraceptives in France

    OpenAIRE

    Tricotel, Aurore; Raguideau, Fanny; Collin, Cédric; Zureik, Mahmoud

    2014-01-01

    PURPOSE: To estimate the number of venous thromboembolic events and related-premature mortality (including immediate in-hospital lethality) attributable to the use of combined oral contraceptives in women aged 15 to 49 years-old between 2000 and 2011 in France. METHODS: French data on sales of combined oral contraceptives and on contraception behaviours from two national surveys conducted in 2000 and 2010 were combined to estimate the number of exposed women according to contraceptives genera...

  13. Oral available agents in the treatment of relapsing remitting multiple sclerosis an overview of merits and culprits

    Directory of Open Access Journals (Sweden)

    Thöne J

    2013-02-01

    Full Text Available Jan Thöne, Gisa Ellrichmann Department of Neurology, St Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany Abstract: Multiple sclerosis (MS is a chronic immunological disease of the central nervous system characterized by early inflammatory demyelination and subsequent neurodegeneration. Major therapeutic progress has occurred during the past decade, in particular since the introduction of immunomodulatory agents, however, MS is still an incurable disease. In addition, parenteral application of the currently licensed drugs is associated with injection-related adverse events (AEs and low patient compliance. Thus, there remains an unmet need for the development of more effective and well tolerated oral therapies for the treatment of MS. A number of new orally administered agents including fingolimod, laquinimod, teriflunomide, cladribine, and BG-12 have been licensed recently or are currently under investigation in relapsing remitting MS patients. In multi-center, randomized, placebo-controlled phase III clinical studies, all of these agents have already shown their efficacy on both clinical disease parameters and magnetic resonance imaging-based measures of disease activity in patients with relapsing remitting MS. However, there are essential differences concerning their clinical efficacy and side-effect profiles. Additionally, the mechanisms by which these substances exert clinical efficacy have not been fully elucidated. In this article, we review the pharmaceutical properties of fingolimod, laquinimod, teriflunomide, cladribine, and BG-12; and their suggested mechanisms of action, clinical efficacy, and side-effect profiles. Keywords: cladribine, fingolimod (FTY, fumaric acid esters (BG-12, laquinimod, teriflunomide

  14. Successful treatment of a large oral verrucous hyperplasia with photodynamic therapy combined with cryotherapy

    Directory of Open Access Journals (Sweden)

    Yu-Chao Chang

    2013-03-01

    Full Text Available Studies have shown that topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT can be used successfully for the treatment of oral verrucous hyperplasia (OVH. Studies have also demonstrated that cryotherapy could be used as a treatment modality for OVH lesions. In this case report, we tested the efficacy of topical ALA-PDT, combined with cryogun cryotherapy, for an extensive OVH lesion on the right buccal mucosa of a 65-year-old male areca quid chewer. The tumor was cleared after six treatments of combined topical ALA-PDT and cryogun cryotherapy. No recurrence of the lesion was found after a follow-up period of 18 months. We suggest that our combined treatment protocol may be effective in treating OVH lesions. The treatment course may be slightly shortened with this combined protocol and was well tolerated by the patient.

  15. DNA repair in human cells exposed to combinations of carcinogenic agents

    International Nuclear Information System (INIS)

    Setlow, R.B.; Ahmed, F.E.

    1980-01-01

    Normal human and XP 2 fibroblasts were treated with uv plus uv-mimetic chemicals. The uv dose used was sufficient to saturate the uv excision repair system. Excision repair after combined treatments was estimated by unscheduled DNA synthesis, BrdUrd photolysis, and the loss of sites sensitive to a uv specific endonuclease. Since the repair of damage from uv and its mimetics is coordinately controlled we expected that there would be similar rate-limiting steps in the repair of uv and chemical damage and that after a combined treatment the total amount of repair would be the same as from uv or the chemicals separately. The expectation was not fulfilled. In normal cells repair after a combined treatment was additive whereas in XP cells repair after a combined treatment was usually less than after either agent separately. The chemicals tested were AAAF, DMBA-epoxide, 4NQO, and ICR-170

  16. Comparison of different combinations of chemotherapy and radiotherapy in patients with cancer of oral cavity and pharynx

    International Nuclear Information System (INIS)

    Kachmar, T.B.

    1999-01-01

    The study involved 341 cases. The use of simultaneous chemoradiotherapy increases total regression of the malignant process by 10% and prolongs survival by 14% in patients with advanced cancer of the oral cavity and pharynx. Neo adjuvant therapy combined with radiotherapy vs radiotherapy alone increases the frequency of total regression by 9% and prolongs the survival by 15% in the patients with cancer of the oral cavity and throat (IV stage, male patients, the tumor located in the oral cavity and oropharynx)

  17. The impact of combined oral contraceptives on ocular tissues: a review of ocular effects

    Directory of Open Access Journals (Sweden)

    Marilita M. Moschos

    2017-10-01

    Full Text Available The aim of this manuscript is to review the action and adverse effects of combined oral contraceptives (COCs on ocular tissues. The percentage of unwanted pregnancies and the subsequent abortions make contraception crucial worldwide. Over 100 million women around the world use common contraceptive methods, including intrauterine devices, combined estrogen and progestin oral contraceptives, as well as progestin only preparations (oral contraceptives, implants or injections. COCs are widely used for contraception, but they are also indicated in menorrhagia, endometriosis, acne and hirsutism, fibroid uterus and premenstrual syndrome. However, they have been associated with high rates of cardiovascular events, venous thromboembolic disease, ischemic strokes and breast cancer. The incidence of COCs-related ocular complications is estimated to be 1 in 230 000, including dry eye symptoms, corneal edema, lens opacities and retinal neuro-ophthalmologic or vascular complications. We may infer that the serious ocular complications of COCs can be prevented by eliminating the estrogen dosage and choosing third-generation progestins. In any case, doctors should take into consideration the systemic and ocular history of the patients before selecting any method of contraception.

  18. MDCT appearance of the appendix: how does the low-density barium sulfate oral contrast agent affect it?

    Science.gov (United States)

    Yaghmai, Vahid; Aghaei-Lasboo, Anahita; Brandwein, Warren M; Tochetto, Sandra; Mafi, John N; Miller, Frank H; Nikolaidis, Paul

    2011-01-01

    We compared the effect of low-density barium sulfate neutral oral contrast agent on the diameter of normal appendix and its luminal content versus that of water on multidetector-row CT. CT scans of 24 patients who had been imaged on two separate occasions for the evaluation of pancreatic pathology, once with water and subsequently with low-density barium sulfate as the neutral oral contrast agent were evaluated (total of 48 scans). Studies were randomized and reviewed in consensus on a workstation in the stack mode by two radiologists blinded to the type of oral contrast. The appendix was measured at baseline and 10 days later to obtain an average diameter. Results of the water and low-density barium sulfate groups were compared using paired t test. Contents of the appendiceal lumen were also noted (gas, fluid, mixed, and collapsed appendix). The average diameter of the appendix for scans obtained with water and low-density barium sulfate was 4.09 ± 0.87 mm (median, 4.22 mm; range, 2.50-5.65 mm) and 4.13 ± 0.93 mm (median, 4 mm, range, 2.2-5.65 mm), respectively. This difference was not statistically significant (P = 0.69). There was no statistically significant difference in the appendiceal content when water or low-density barium sulfate were used as oral contrast (χ (2) = 4.25, P = 0.89). Low-density barium sulfate does not affect appendiceal content or diameter and, therefore, should not adversely affect evaluation of the appendix on multidetector row CT.

  19. Oral Candida in Patients with Fixed Orthodontic Appliance: In Vitro Combination Therapy.

    Science.gov (United States)

    Alhamadi, Wisam; Al-Saigh, Rafal J; Al-Dabagh, Nebras N; Al-Humadi, Hussam W

    2017-01-01

    Fixed orthodontic appliance (FOA) increases the cariogenic microorganisms of mouth including candida. The aim was to evaluate the pharmacodynamic effects of some antibacterial drugs in combination with most applicable antifungal agents on candida isolated from patients with FOA. Three antifungal agents (amphotericin B (AMB), ketoconazole (KET), and itraconazole (ITZ)) and three antibacterial drugs (ciprofloxacin (CIP), doxycycline (DOX), and metronidazole (MET)) with serial concentrations have been used and microdilution broth method has been done for single and combination therapy, then fungal growth was assessed spectrophotometrically, and the combinations were evaluated by bliss independent analysis. According to bliss independent interaction, the synergistic interactions depended on Δ E values that showed the best for CIP was with AMB (Δ E = 55.14) followed with KET (Δ E = 41.23) and lastly ITR (Δ E = 39.67) at CIP = 150 mg/L. DOX was optimal with KET (Δ E = 42.11) followed with AMB (Δ E = 40.77) and the lowest with ITR (Δ E = 9.12) at DOX = 75 mg/L. MET is the best with AMB (Δ E = 40.95) and then with ITR (Δ E = 35.45) and finally KET (Δ E = 15.15) at MET 200 mg/L. Moreover, usage of higher concentrations of antibacterial agents revealed inhibitory effects. This study uncovers the optimum antibiotic combination therapy against cariogenic candida with FOA by usage of low therapeutic concentrations.

  20. Dosage and dose schedule screening of drug combinations in agent-based models reveals hidden synergies

    Directory of Open Access Journals (Sweden)

    Lisa Corina Barros de Andrade e Sousa1

    2016-01-01

    Full Text Available The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.

  1. Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients

    DEFF Research Database (Denmark)

    Jensen, Siri Beier; Jarvis, Virginia; Zadik, Yehuda

    2013-01-01

    /or conflicting evidence. CONCLUSIONS: None of the agents reviewed was determined to be effective for the prevention or treatment of OM. Two agents, pilocarpine and pentoxifylline, were determined to be ineffective, in the populations listed above. Additional well-designed research is needed on other...

  2. Enhanced oral bioavailability of docetaxel in rats combined with myricetin: In situ and in vivo evidences.

    Science.gov (United States)

    Hao, Tianyun; Ling, Yunni; Wu, Meijuan; Shen, Yajing; Gao, Yu; Liang, Shujun; Gao, Yuan; Qian, Shuai

    2017-04-01

    The purpose of this study was to investigate the effect of myricetin on the pharmacokinetics of docetaxel in rats. In comparison to oral docetaxel alone (40mg/kg), the bioavailability of docetaxel could be significantly enhanced by 1.6-2.4-fold via oral co-administration with various flavonoids (apigenin, naringenin, baicalein, quercetin and myricetin) at a dosage of 10mg/kg, and myricetin showed the highest bioavailability improvement. Further pharmacokinetic studies demonstrated that the presence of myricetin (5-20mg/kg) enhanced both C max and AUC of docetaxel with the highest C max (162ng/mL, 2.3-fold) and relative bioavailability (244%) achieved at 10mg/kg of myricetin, while t 1/2 was not influenced. In order to explore the reasons for such bioavailability enhancement of docetaxel, rat in situ single-pass intestinal perfusion model and intravenous docetaxel co-administrated with oral myricetin were carried out. After combining with myricetin, the permeability coefficient (P blood ) of docetaxel based on its appearance in mesenteric blood was significantly increased up to 3.5-fold in comparison to that of docetaxel alone. Different from oral docetaxel, the intravenous pharmacokinetics of docetaxel was not affected by co-administration of myricetin, indicating the limited effect of myricetin on the elimination of docetaxel. The above findings suggested that the oral bioavailability enhancement of docetaxel via co-administration with myricetin might be mainly attributed to the enhanced absorption in gastrointestinal tract rather than modulating the elimination of docetaxel. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Combination of retrograde superselective intra-arterial chemotherapy and Seldinger method in locally advanced oral cancer

    Directory of Open Access Journals (Sweden)

    Masataka Uehara

    2015-01-01

    Full Text Available The nonsurgical strategies for locally advanced oral cancer are desirable. Superselective intra-arterial infusion with radiotherapy was utilized for this purpose, and there are two types of superselective intra-arterial infusion methods: The Seldinger method and the retrograde superselective intra-arterial chemotherapy (HFT method. In one case, the HFT method was applied to locally advanced tongue cancer, and the Seldinger method was used for additional administration of cisplatin (CDDP to compensate for a lack of drug flow in the HFT method. In another case, the HFT method was applied to locally advanced lower gingival cancer. The Seldinger method was applied to metastatic lymph nodes. In both cases, additional administration of CDDP using the Seldinger method resulted in a complete response. The combination of the HFT and Seldinger methods was useful to eradicate locally advanced oral cancer because each method compensated for the defects of the other.

  4. Time, dose and volume factors in interstitial brachytherapy combined with external irradiation for oral tongue carcinoma

    International Nuclear Information System (INIS)

    Yorozu, Atsunori

    1996-01-01

    This is a retrospective analysis of 136 patients with squamous cell carcinoma of stages I and II of the oral tongue who were treated with interstitial brachytherapy alone or in combination with external irradiation between 1976 and 1991. Control of the primary lesion and the occurrence of late complications were analyzed with respect to dose, time and tumor size with the Cox hazard model. The 5-year survival rates for stages I and II were 84.5% and 75.6%. The 5-year primary control rate was 91.3% for stage I and 77.3% for stage II (p 50 Gy compared with a brachytherapy dose 30 mm. Late complications should be reduced by using a spacer, improvements in dental and oral hygiene, and a sophisticated implant method. (author)

  5. Adherence to Rivaroxaban Compared with Other Oral Anticoagulant Agents Among Patients with Nonvalvular Atrial Fibrillation.

    Science.gov (United States)

    McHorney, Colleen A; Ashton, Veronica; Laliberté, François; Germain, Guillaume; Wynant, Willy; Crivera, Concetta; Schein, Jeffrey R; Lefebvre, Patrick; Peterson, Eric D

    2017-09-01

    Adherence to oral anticoagulant (OAC) agents is important for patients with nonvalvular atrial fibrillation (NVAF) to prevent potentially severe adverse events. To compare real-world adherence rates and time to discontinuation for rivaroxaban versus other OACs (apixaban, dabigatran, and warfarin) among patients with NVAF using claims-based data. Health care claims from the IMS Health Real-World Data Adjudicated Claims database (July 2012-June 2015) were analyzed. Adherence rate was defined as the percentage of patients with proportion of days covered (PDC) ≥ 0.80 and ≥ 0.90. Discontinuation was defined as a gap of more than 30 days between the end of a dispensing days of supply and the start date of the next fill, if any. Patients were included if they had ≥ 2 dispensings of rivaroxaban, apixaban, dabigatran, or warfarin at least 180 days apart (the first was considered the index date), had > 60 days of supply, had ≥ 6 months of pre-index eligibility, had ≥ 1 atrial fibrillation (AF) diagnosis pre-index or at index date, and had no valvular involvement. A logistic regression model was used to evaluate adherence to OAC therapy, while a Cox model was used to compare time to discontinuation; both models adjusted for baseline confounders. A total of 13,645 rivaroxaban, 6,304 apixaban, 3,360 dabigatran, and 13,366 warfarin patients were identified. A significantly higher proportion of rivaroxaban users (80.1%) was adherent to therapy (PDC ≥ 0.80 at 6 months) versus apixaban (75.8%), dabigatran (69.2%), and warfarin users (64.5%). After adjustment, the proportion of patients adherent to therapy remained significantly higher for rivaroxaban users versus apixaban (absolute difference [AD] = 5.8%), dabigatran (AD = 9.5%), and warfarin users (AD = 13.6%; all P 0.80 or > 0.90. Such differences in adherence could translate into improved patient outcomes and lower health care costs. This research was funded by Janssen Scientific Affairs. Ashton, Crivera, and Schein

  6. Radiotherapy with radiomodifying agents of carcinoma of the oral cavity organs and stomatopharynx

    International Nuclear Information System (INIS)

    Vorob'ev, Yu.I.; Dzharadat, I.

    1992-01-01

    The results of radiotherapy are compared in three identical groups of patients with squamous-cell carcinoma of the oral cavity organs and stomatoparynx (a total of 149 patients). Metronidazole radiomodification was carried out in a dose of 2.5 g/m 2 body surface orally 3 hrs before hyperthermia or thermoradiotherapy with a 30 min warming up before radiation exposure. Radiotherapy with polyradiomodification had no advantages as against thermoradiotherapy. Thermoradiotherapy alone and polyradiomodification provided cure (as evidenced by an 18 month follow-up) in patients with stage 3 condition in 54.3±7.3 % of cases, wheras radiotherapy alone in but 21.9±5.3 % of cases. The results of treatment making use of radiomodifiers were no better than the results of radiotherapy alone in patients with stage 4 carcinomas of the oral cavity organs and stomatopharynx

  7. Treatment of Aluminium Phosphide Poisoning with a Combination of Intravenous Glucagon, Digoxin and Antioxidant Agents

    Directory of Open Access Journals (Sweden)

    Zohreh Oghabian

    2016-08-01

    Full Text Available Aluminium phosphide (AlP is used to protect stored grains from rodents. It produces phosphine gas (PH3, a mitochondrial poison thought to cause toxicity by blocking the cytochrome c oxidase enzyme and inhibiting oxidative phosphorylation, which results in cell death. AlP poisoning has a high mortality rate among humans due to the rapid onset of cardiogenic shock and metabolic acidosis, despite aggressive treatment. We report a 21-yearold male who was referred to the Afzalipour Hospital, Kerman, Iran, in 2015 after having intentionally ingested a 3 g AlP tablet. He was successfully treated with crystalloid fluids, vasopressors, sodium bicarbonate, digoxin, glucagon and antioxidant agents and was discharged from the hospital six days after admission in good clinical condition. For the treatment of AlP poisoning, the combination of glucagon and digoxin with antioxidant agents should be considered. However, evaluation of further cases is necessary to optimise treatment protocols.

  8. Research on a new oral contrast agent for abdominal MRI using free manganese ion

    International Nuclear Information System (INIS)

    Hasegawa, Hideo; Fujita, Osamu; Hiraishi, Kumiko; Narabayashi, Isamu; Komba, Toshinori; Hamamura, Yoshinori.

    1996-01-01

    Manganese chloride (Mn: 3 mg/100 g) aqueous solution with hydragenated oligosaccharide and xanthan gum (T 1 : 0.1 sec, T 2 : 0.03 sec at 0.5T) functions in gut as a positive contrast agent on MR T 1 -weighted images and a low signal component on MR T 2 -weighted images. The manganese in the solution functions as a contrast agent under free manganese ion (Mn 2+ ). Further, the solution has special characteristics in terms of MRI signal intensity and relaxation time that are equal to those of blueberry juice, which performs as an effective contrast agent on T 1 -and T 2 -weighted images, and functions as a contrast agent in vitro and in vivo. (author)

  9. Comparison of oral Midazolam-Ketamine and Midazolam-Promethazine as sedative agents in pediatric dentistry

    Directory of Open Access Journals (Sweden)

    Mojtaba Vahid Golpayegani

    2012-01-01

    Conclusion: Under the current circumstances, Ketamine/Midazolam combination provided sufficient sedative effect in lower doses. However, Midazolam/Promethazine combination did not produce similar results.

  10. Combined oral contraceptives' influence on weight, body composition, height, and bone mineral density in girls younger than 18 years

    DEFF Research Database (Denmark)

    Warholm, Lina; Petersen, Kresten R; Ravn, Pernille

    2012-01-01

    Combined oral contraceptives (COCs) are increasingly used by adolescents. The aim of this review is to investigate the evidence regarding COCs' influence on weight, height and bone mineral density (BMD) in girls younger than 18 years.......Combined oral contraceptives (COCs) are increasingly used by adolescents. The aim of this review is to investigate the evidence regarding COCs' influence on weight, height and bone mineral density (BMD) in girls younger than 18 years....

  11. Suspension culture combined with chemotherapeutic agents for sorting of breast cancer stem cells

    International Nuclear Information System (INIS)

    Li, Hai-zhi; Yi, Tong-bo; Wu, Zheng-yan

    2008-01-01

    Cancer stem cell (CSC) hypothesis has not been well demonstrated by the lack of the most convincing evidence concerning a single cell capable of giving rise to a tumor. The scarcity in quantity and improper approaches for isolation and purification of CSCs have become the major obstacles for great development in CSCs. Here we adopted suspension culture combined with anticancer regimens as a strategy for screening breast cancer stem cells (BrCSCs). BrCSCs could survive and be highly enriched in non-adherent suspension culture while chemotherapeutic agents could destroy most rapidly dividing cancer cells and spare relatively quiescent BrCSCs. TM40D murine breast cancer cells were cultured in serum-free medium. The expression of CD44 + CD24 - was measured by flow cytometry. Cells of passage 10 were treated in combination with anticancer agents pacilitaxel and epirubicin at different peak plasma concentrations for 24 hours, and then maintained under suspension culture. The rate of apoptosis was examined by flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining method. Selected cells in different amounts were injected subcutaneously into BALB/C mice to observe tumor formation. Cells of passage 10 in suspension culture had the highest percentage of CD44 + CD24 - (about 77 percent). A single tumor cell in 0.35 PPC could generate tumors in 3 of 20 BALB/C mice. Suspension culture combined with anticancer regimens provides an effective means of isolating, culturing and purifying BrCSCs

  12. The use of anaesthetic agents to provide anxiolysis and sedation in dentistry and oral surgery

    OpenAIRE

    O'Halloran, Michael

    2013-01-01

    Throughout the world there is considerable variation in the techniques used to manage anxious dental patients requiring treatment. Traditionally anxious or phobic dental patients may have been sent for general anaesthesia to allow dental treatment be undertaken. While this is still the case for the more invasive oral surgical procedures, such as wisdom teeth extraction, sedation in general dentistry is becoming more popular.

  13. Analysis of incidence and nursing care for oral adverse events induced by chest or pelvic irradiation combined with chemotherapy

    International Nuclear Information System (INIS)

    Seki, Miyuki; Kitada, Yoko; Ishikawa, Hitoshi

    2010-01-01

    The aim of this study was to clarify incidence and severity of oral adverse events induced by chemoradiotherapy and to explore efficient nursing-intervention or oral-care for the oral complications. Seventy-nine subjects who were treated with chemoradiotherapy at the radiation oncology unit of Gunma University Hospital were retrospectively analyzed using collected data from patients' medical chart including location of tumor, details of treatment, incidence and care of oral adverse events. Oral adverse events occurred in 7 (9%) of 79 patients. The complication rate in patients with lung or esophageal cancer was much higher than that with rectal or cervical cancer. All patients with the events received a total irradiation dose of 60 Gy in 30 fractions or higher. Oral mucositis was observed in 5 patients given antimetabolic chemotherapeutic agents, but they were successfully treated with steroids and/or gargles. Our results suggest that early intervention of oral care may reduce risks of developing severe oral adverse effects induced by chemoradiotherapy. (author)

  14. Results of combined modality treatment in patients with primary unresectable cancer of the oral cavity

    International Nuclear Information System (INIS)

    Kawecki, A.; Starosciak, S.; Towpik, E.; Jagielska, B.; Lenartowicz, B.; Pietras, M.; Szutkowski, Z.; Kiprian, D.

    2001-01-01

    Neoadjuvant chemotherapy may improve the results of treatment for primarily unresectable cancer of the oral cavity. The aim of this study was to estimate the tolerance and early results of neoadjuvant chemotherapy followed by surgical resection of oral cavity cancer, with immediate reconstruction and adjuvant radiotherapy. 56 patients hospitalized at the Department of Head and Neck Cancer of the Maria Sklodowska-Curie Memorial Cancer Centre - Institute of Oncology between August 1997 and June 2000 were enrolled for the purpose of the study. When tumour regresion was observed after 2-4 courses of neoadjuvant chemotherapy consisting of cisplatin, 5-fluorouracil, methotrexate, vinblastin, etoposide and leucovorin, the patients were referred for surgical resection with immediate reconstruction, followed by adjuvant radiotherapy. Regression of the primary tumor and lymph nodes of the neck was observed in 41 patients, all of whom were referred for radical surgery followed by adjuvant radiotherapy. The tolerance of combined treatment was acceptable. Complete regression was obtained in 37/56 patients. During observation 12 patients failed due to locoregional progression and 2 due to distant metastases. 23/56 patients (41 %) are alive without evidence of disease. Neoadjuvant chemotherapy allows for radical resection in a majority of patients with primarily unresectable cancer of the oral cavity. The tolerance of treatment is good. What is important, radiotherapy and chemotherapy do not impair wound healing and vascularity of musculo-cutaneous island flaps

  15. Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

    Directory of Open Access Journals (Sweden)

    Jensen JT

    2013-11-01

    Full Text Available Jeffrey T Jensen,1 Johannes Bitzer,2 Marco Serrani3 1Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; 2Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; 3Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany Abstract: Three estradiol (E2-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA, Femilar®, estradiol valerate/dienogest (E2V/DNG, Qlaira®/Natazia™, and estradiol/nomegestrol acetate (E2/NOMAC; Zoely®, have received approval for use in general practice. Only Finnish women currently have access to all three E2-based formulations. E2/NOMAC is currently approved only in Europe, while E2V/DNG is approved globally. To assist clinicians counseling women considering use of one of these formulations, we conducted a review of the published information about the current E2-containing oral contraceptives. A literature search was conducted using the Ovid interface and a combination of free search terms relevant to estradiol and oral contraception to identify suitable articles for inclusion in this review. The available data show that E2V/DNG, E2/NOMAC, and E2V/CPA are all effective oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E2V/DNG and E2/NOMAC may have better bleeding profiles than E2V/CPA. E2V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E2V/DNG and E2/NOMAC have minimal influence on hemostatic, lipid, and carbohydrate metabolism parameters, or induce less change in these parameters relative to ethinylestradiol-based oral contraceptives. However, the predictive value of these surrogate parameters is a matter of debate, and whether these differences can be translated into meaningful clinical outcomes needs to be established in large-scale, post-marketing, prospective, Phase IV cohort

  16. Oral combination therapy: repaglinide plus metformin for treatment of type 2 diabetes.

    Science.gov (United States)

    Raskin, P

    2008-12-01

    Type 2 diabetes is characterized by decreases in insulin secretion and insulin sensitivity. Several classes of oral antidiabetic medications are currently approved for the treatment of type 2 diabetes. A stepwise treatment approach from monotherapy to combination therapy is traditionally used; however, the frequency of treatment failure with monotherapy has resulted in a move towards earlier treatment with combination therapies that target the two principal defects in glycaemic control. One such combination regimen is repaglinide (a prandial glucose regulator that increases insulin release) plus metformin (an insulin sensitizer that inhibits hepatic glucose output, increases peripheral glucose uptake and utilization and minimizes weight gain). Findings from several clinical trials have shown that combination therapy with repaglinide plus metformin is well tolerated and results in greater reductions of haemoglobin A(1c) and fasting plasma glucose values compared with either monotherapy. Repaglinide may also provide a more suitable alternative to combination therapy with sulphonylureas and metformin because of its reduced propensity for hypoglycaemia. The combination regimen of repaglinide plus metformin should therefore be considered as a valuable option in the management of patients with type 2 diabetes when monotherapy is no longer adequate.

  17. Distribution and drivers of costs in type 2 diabetes mellitus treated with oral hypoglycemic agents: a retrospective claims data analysis.

    Science.gov (United States)

    Bron, Morgan; Guerin, Annie; Latremouille-Viau, Dominick; Ionescu-Ittu, Raluca; Viswanathan, Prabhakar; Lopez, Claudia; Wu, Eric Q

    2014-09-01

    To describe the distribution of costs and to identify the drivers of high costs among adult patients with type 2 diabetes mellitus (T2DM) receiving oral hypoglycemic agents. T2DM patients using oral hypoglycemic agents and having HbA1c test data were identified from the Truven MarketScan databases of Commercial and Medicare Supplemental insurance claims (2004-2010). All-cause and diabetes-related annual direct healthcare costs were measured and reported by cost components. The 25% most costly patients in the study sample were defined as high-cost patients. Drivers of high costs were identified in multivariate logistic regressions. Total 1-year all-cause costs for the 4104 study patients were $55,599,311 (mean cost per patient = $13,548). Diabetes-related costs accounted for 33.8% of all-cause costs (mean cost per patient = $4583). Medical service costs accounted for the majority of all-cause and diabetes-related total costs (63.7% and 59.5%, respectively), with a minority of patients incurring >80% of these costs (23.5% and 14.7%, respectively). Within the medical claims, inpatient admission for diabetes-complications was the strongest cost driver for both all-cause (OR = 13.5, 95% CI = 8.1-23.6) and diabetes-related costs (OR = 9.7, 95% CI = 6.3-15.1), with macrovascular complications accounting for most inpatient admissions. Other cost drivers included heavier hypoglycemic agent use, diabetes complications, and chronic diseases. The study reports a conservative estimate for the relative share of diabetes-related costs relative to total cost. The findings of this study apply mainly to T2DM patients under 65 years of age. Among the T2DM patients receiving oral hypoglycemic agents, 23.5% of patients incurred 80% of the all-cause healthcare costs, with these costs being driven by inpatient admissions, complications of diabetes, and chronic diseases. Interventions targeting inpatient admissions and/or complications of diabetes may contribute to the decrease of the

  18. Predicting the oral uptake efficiency of chemicals in mammals: Combining the hydrophilic and lipophilic range

    Energy Technology Data Exchange (ETDEWEB)

    O' Connor, Isabel A., E-mail: i.oconnor@science.ru.nl [Radboud University Nijmegen, Institute for Water and Wetland Research, Department of Environmental Science, P.O. Box 9010, NL-6500 GL, Nijmegen (Netherlands); Huijbregts, Mark A.J., E-mail: m.huijbregts@science.ru.nl [Radboud University Nijmegen, Institute for Water and Wetland Research, Department of Environmental Science, P.O. Box 9010, NL-6500 GL, Nijmegen (Netherlands); Ragas, Ad M.J., E-mail: a.ragas@science.ru.nl [Radboud University Nijmegen, Institute for Water and Wetland Research, Department of Environmental Science, P.O. Box 9010, NL-6500 GL, Nijmegen (Netherlands); Open University, School of Science, P.O. Box 2960,6401 DL Heerlen (Netherlands); Hendriks, A. Jan, E-mail: a.j.hendriks@science.ru.nl [Radboud University Nijmegen, Institute for Water and Wetland Research, Department of Environmental Science, P.O. Box 9010, NL-6500 GL, Nijmegen (Netherlands)

    2013-01-01

    Environmental risk assessment requires models for estimating the bioaccumulation of untested compounds. So far, bioaccumulation models have focused on lipophilic compounds, and only a few have included hydrophilic compounds. Our aim was to extend an existing bioaccumulation model to estimate the oral uptake efficiency of pollutants in mammals for compounds over a wide K{sub ow} range with an emphasis on hydrophilic compounds, i.e. compounds in the lower K{sub ow} range. Usually, most models use octanol as a single surrogate for the membrane and thus neglect the bilayer structure of the membrane. However, compounds with polar groups can have different affinities for the different membrane regions. Therefore, an existing bioaccumulation model was extended by dividing the diffusion resistance through the membrane into an outer and inner membrane resistance, where the solvents octanol and heptane were used as surrogates for these membrane regions, respectively. The model was calibrated with uptake efficiencies of environmental pollutants measured in different mammals during feeding studies combined with human oral uptake efficiencies of pharmaceuticals. The new model estimated the uptake efficiency of neutral (RMSE = 14.6) and dissociating (RMSE = 19.5) compounds with logK{sub ow} ranging from − 10 to + 8. The inclusion of the K{sub hw} improved uptake estimation for 33% of the hydrophilic compounds (logK{sub ow} < 0) (r{sup 2} = 0.51, RMSE = 22.8) compared with the model based on K{sub ow} only (r{sup 2} = 0.05, RMSE = 34.9), while hydrophobic compounds (logK{sub ow} > 0) were estimated equally by both model versions with RMSE = 15.2 (K{sub ow} and K{sub hw}) and RMSE = 15.7 (K{sub ow} only). The model can be used to estimate the oral uptake efficiency for both hydrophilic and hydrophobic compounds. -- Highlights: ► A mechanistic model was developed to estimate oral uptake efficiency. ► Model covers wide logK{sub ow} range (- 10 to + 8) and several mammalian

  19. Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk.

    Science.gov (United States)

    Maxwell, G L; Schildkraut, J M; Calingaert, B; Risinger, J I; Dainty, L; Marchbanks, P A; Berchuck, A; Barrett, J C; Rodriguez, G C

    2006-11-01

    Using data from a case-control study of endometrial cancer, we investigated the relationship between the progestin and estrogen potency in combination oral contraceptives (OCs) and the risk of developing endometrial cancer. Subjects included 434 endometrial cancer cases and 2,557 controls identified from the Cancer and Steroid Hormone (CASH) study. OCs were classified into four categories according to the individual potencies of each hormonal constituent (high versus low estrogen or progestin potency). Logistic regression was used to evaluate associations between endometrial cancer risk and combination OC formulations. With non-users as the referent group, use of OCs with either high potency progestin [odds ratio for endometrial cancer (OR)=0.21, 95% confidence interval (CI)=0.10 to 0.43] or with low potency progestin (OR=0.39, 95% CI=0.25 to 0.60) were both associated with a decreased risk of endometrial cancer. Overall high progestin potency OCs did not confer significantly more protection than low progestin potency OCs (OR=0.52, 95% CI=0.24 to 1.14). However, among women with a body mass index of 22.1 kg/m2 or higher, those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31, 95% CI=0.11 to 0.92) while those with a BMI below 22.1 kg/m2 did not (OR=1.36, 95% CI=0.39 to 4.70). The potency of the progestin in most OCs appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OCs may be more protective than lower progestin potency OCs among women with a larger body habitus.

  20. Prognostic value and importance of surgery combined with postoperative radiotherapy for oral and oropharyngeal cancer

    International Nuclear Information System (INIS)

    Maciejewski, A.

    2001-01-01

    The aim of this paper is to evaluate the efficacy of surgery for patients with oral cavity or oropharyngeal cancer, and is impact on the final results of treatment combined with postoperative radiotherapy. Furthermore, predictive and prognostic value of clinical and histopatological postoperative factors were analysed, and estimation of clinical applicability of modified scale for risk of postoperative local and/or nodal recurrence according to Peters was checked. Material includes 218 cases of the advanced oral cavity or oropharyngeal cancer. All data were subdivided into 4 groups depending on treatment strategy. For the analysis of the treatment efficacy (overall and disease-free survival) many predictive and prognostic factors have been considered. Despite of multivariate logistic regression analysis of these factors, the risk of local recurrence was related to the results of combined treatment based on the modified numerical risk scale adapted from Peters. The risk value is the sum of scores given to individual prognostic factors. Time interval between surgery and radiotherapy (TI) and overall treatment time (TTT) have been accounted for the analysis. Generally; optimal results were noted in the group B, where surgery has been combined with postoperative radiotherapy. In case of surgery combined with preoperative radiotherapy (group E) 5-year DFS was 30%, and in the case when radiotherapy was delayed and applied when recurrence after primary surgery has occurred, the 5-year DFS was not higher than 20%. Macro- and microscopic surgical radicalism has been found one of the most important and significant prognostic factors. For positive margins (m+) 5-year DFS significantly decreases to about 20%. Surgical macro- and microradicalism has an important impact (p = 0.013) on the incidence of distant metastases. The scoring system for the recurrence was based on Peters scale. The sum of the risk scores (TRRI+n) for individual prognostic factors allow to allocate

  1. Biological effects of radiation in combination with other physical, chemical or biological agents. Annex L

    International Nuclear Information System (INIS)

    1982-01-01

    This Annex considers the combined action of radiation with potentially important environmental conditions. Since there is a scarcity of systematic data on which an analysis of combined effects can be based, this Annex will be more hypothetical and will attempt to suggest definitions, to identify suitable methods of analysis, to select from a large amount of diffuse information the conditions and the data of importance for further consideration and to provide suggestions for future research. For humans in environmental circumstances the UNSCEAR Committee has been unable to document any clear case of synergistic interaction between radiation and other agents, which could lead to substantial modifications of the risk estimates for significant sections of the population.

  2. The combined effect of interferon synthesis inductors, radiosensitizing and antitumoral agents on solid tumors

    International Nuclear Information System (INIS)

    Leonidze, D.L.

    1987-01-01

    In experiments with mice bearing solid sarcoma 37 a study was conducted on the combined effect of radiation and inductors of endogenous inerferon synthesis (IEIS), together with hyperthermia or together with an alkylating and carbomoilating agent, dimethinur. The effect was estimated by the tumor growth coefficient and by the number of animals with the regressed tumors. Poly I; polyC was not shiown to influence the efficiency of hyperthermia combined with radiation with radiation; dextransulphate and tiloron increased the radiosensitizing effect of hyperthermia. Dimethinur aggravated the effect of radiation, but with IEIS used together with dimethynur and radiation, the response of the tumor increased insignificantly as compared to the effect of IEIS together with radiation

  3. Combining Bayesian Networks and Agent Based Modeling to develop a decision-support model in Vietnam

    Science.gov (United States)

    Nong, Bao Anh; Ertsen, Maurits; Schoups, Gerrit

    2016-04-01

    Complexity and uncertainty in natural resources management have been focus themes in recent years. Within these debates, with the aim to define an approach feasible for water management practice, we are developing an integrated conceptual modeling framework for simulating decision-making processes of citizens, in our case in the Day river area, Vietnam. The model combines Bayesian Networks (BNs) and Agent-Based Modeling (ABM). BNs are able to combine both qualitative data from consultants / experts / stakeholders, and quantitative data from observations on different phenomena or outcomes from other models. Further strengths of BNs are that the relationship between variables in the system is presented in a graphical interface, and that components of uncertainty are explicitly related to their probabilistic dependencies. A disadvantage is that BNs cannot easily identify the feedback of agents in the system once changes appear. Hence, ABM was adopted to represent the reaction among stakeholders under changes. The modeling framework is developed as an attempt to gain better understanding about citizen's behavior and factors influencing their decisions in order to reduce uncertainty in the implementation of water management policy.

  4. Efficacy and safety of combined ethinyl estradiol/drospirenone oral contraceptives in the treatment of acne

    Directory of Open Access Journals (Sweden)

    Jerry KL Tan

    2009-11-01

    Full Text Available Jerry KL Tan1, Chemanthi Ediriweera21University of Western Ontario and Windsor Clinical Research Inc., Windsor, Ontario, Canada; 2University of Western Ontario, Southwest Ontario Medical Education Network, Windsor, Ontario, CanadaAbstract: Acne is a common disorder affecting the majority of adolescents and often extends into adulthood. The central pathophysiological feature of acne is increased androgenic stimulation and/or end-organ sensitivity of pilosebaceous units leading to sebum hypersecretion and infundibular hyperkeratinization. These events lead to Propionibacterium acnes proliferation and subsequent inflammation. Hormonal therapy, including combined oral contraceptives (OCs, can attenuate the proximate androgenic trigger of this sequence. For many women, hormonal therapy is a rational option for acne treatment as it may be useful across the spectrum of severity. Drospirenone (DRSP is a unique progestin structurally related to spironolactone with progestogenic, antimineralocorticoid, and antiandrogenic properties. It is available in 2 combined OC preparations (30 µg EE/3 mg DRSP; Yasmin® in a 21/7 regimen; and 20 µg EE/3 mg DRSP; Yaz® in a 24/4 regimen. These preparations are bereft of the fluid retentional side effects typical of other progestins and their safety has been demonstrated in large epidemiological studies in which no increased risk of vascular thromboembolic disease or arrhythmias was observed. In acne, the efficacy of DRSP-containing OCs has been shown in placebo-controlled superiority trials and in active-comparator non-inferiority trials.Keywords: acne vulgaris, combined oral contraceptives, drosperinone, ethinyl estradiol, efficacy, safety, treatment

  5. Radiation dose estimates for oral agents used in upper gastrointestinal disease

    International Nuclear Information System (INIS)

    Siegel, J.A.; Wu, R.K.; Knight, L.C.; Zelac, R.E.; Stern, H.S.; Malmud, L.S.

    1983-01-01

    Radiation dosimetry was calculated for a number of orally administered radiopharmaceuticals used for study of upper gastrointestinal function. These include: Tc-99m sulfur colloid in water, in a cooked egg, and in chicken liver labeled in vivo; In-111 DTPA; Tc-99m DTPA; In-113m DTPA; Tc-99m ovalbumin in cooked egg; and In-111 colloid in chicken liver labeled in vivo. Radiation burdens to the stomach, small intestine, upper and lower large intestine, ovaries, testes, and total body are calculated for each preparation

  6. The role of bleomycin combination in radiation therapy for squamous cell carcinoma in the oral cavity

    International Nuclear Information System (INIS)

    Masaki, Norie

    1986-01-01

    In an effort to improve tumor control by radiation therapy, a treatment regimen consisting of concurrent combination of bleomycin (90 mg/3 weeks) and radiation (30 Gy/3 weeks) was applied. Between 1972 and 1981, 287 patients with squamous cell carcinoma in the oral cavity were subjected to this bleomycin-radiation combination regimen. All except 4 patients experienced marked response after treatment using the bleomycin-radiation combination alone. One hundred thirty-four patients (47 %) obtained CR and 149 (53 %) PR. Higher CR rates were obtained in patients with carcinoma of the lower gum (62 %), of the upper gum (68 %), and of the cheek mucosa (43 %), compared to patients with carcinoma of the floor of the mouth (21 %), and of the tongue (15 %). In each of the tumor sites, small lesions (T1, T2) obtained higher CR rates, compared with large lesions (T3, T4). Of the 134 patients who experienced CR, 83 were observed without any further treatment after bleomycin-radiation combination alone. Local recurrence-free rates of these patients were 72 % for T1, T2 lesions and 48 % for T3, T4 lesions. Local control rates were increased to 85 % and 78 %, respectively, with successful salvage treatment involving surgery or interstitial radiotherapy for post-irradiation failures. (author)

  7. Absorption and disposition of LY127210, an orally effective hypotensive agent, in laboratory animals

    International Nuclear Information System (INIS)

    Turner, J.C.; White, J.F.; Sullivan, H.R.

    1986-01-01

    The disposition, pharmacokinetics, and metabolic fate of LY127210, 7,8-dimethoxy-(1H)-3-benzazepin-2-amine hydrochloride, have been studied in mice, rats, dogs and monkeys. Pharmacokinetic and bioavailability studies in dogs and monkeys showed it to be well absorbed orally with maximum plasma levels of drug obtained within 4 hr. Following administration of 14 C-LY127210, the plasma half-lives of parent and radiocarbon in rat were 11 hr and 45 hr (β-phase), respectively. In dogs and monkeys parent half-lives were 11 hr (β-phase) and 5.2 hr (monophasic) while half-lives of total radiocarbon were 145 hr (β-phase) and 299 hr (β-phase), respectively. Plasma concentrations of parent compound in rat, dog, and monkey following oral administration accounted for approximately 15% of circulating radiocarbon. Renal excretion was the major route of elimination. The major urinary species was LY127210; metabolic mechanisms included oxidative O-demethylation and deamination, aliphatic oxidation, and reduction. Radiocarbon tissue level studies in rat indicated wide distribution of drug and/or metabolites. Similar studies in monkeys indicated that the half-life of radiocarbon in tissues was equal to or greater than that in plasma and red blood cells. The long half-life of radiocarbon in blood was due to irreversible dose dependent binding of drug and/or metabolites to plasma albumin and to cellular hemoglobin

  8. Optimization of 2-Anilino 4-Amino Substituted Quinazolines into Potent Antimalarial Agents with Oral in Vivo Activity.

    Science.gov (United States)

    Gilson, Paul R; Tan, Cyrus; Jarman, Kate E; Lowes, Kym N; Curtis, Joan M; Nguyen, William; Di Rago, Adrian E; Bullen, Hayley E; Prinz, Boris; Duffy, Sandra; Baell, Jonathan B; Hutton, Craig A; Jousset Subroux, Helene; Crabb, Brendan S; Avery, Vicky M; Cowman, Alan F; Sleebs, Brad E

    2017-02-09

    Novel antimalarial therapeutics that target multiple stages of the parasite lifecycle are urgently required to tackle the emerging problem of resistance with current drugs. Here, we describe the optimization of the 2-anilino quinazoline class as antimalarial agents. The class, identified from publicly available antimalarial screening data, was optimized to generate lead compounds that possess potent antimalarial activity against P. falciparum parasites comparable to the known antimalarials, chloroquine and mefloquine. During the optimization process, we defined the functionality necessary for activity and improved in vitro metabolism and solubility. The resultant lead compounds possess potent activity against a multidrug resistant strain of P. falciparum and arrest parasites at the ring phase of the asexual stage and also gametocytogensis. Finally, we show that the lead compounds are orally efficacious in a 4 day murine model of malaria disease burden.

  9. 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.

  10. The influence of combined oral contraceptives on female sexual desire: a systematic review.

    Science.gov (United States)

    Pastor, Zlatko; Holla, Katerina; Chmel, Roman

    2013-02-01

    To determine the relationship between the use of combined oral contraceptives (COCs) and sexual desire based on a systematic review of the literature. MEDLINE Complete, Google Scholar and the Cochrane Library were searched for articles published between 1975 and 2011, reporting the effects of oral contraceptives on sexual desire. Reports fully meeting all the predefined criteria were analysed and included in a final reference list. In addition, a review of the reference list of selected articles was carried out. We evaluated 36 studies (1978-2011; 13,673 women). Of the COC users (n = 8,422), 85% reported an increase (n = 1,826) or no change (n = 5,358) in libido and 15% reported a decrease (n = 1,238). We found no significant difference in sexual desire in the case of COCs with 20-35 μg ethinylestradiol; libido decreased only with pills containing 15 μg ethinylestradiol. The majority of COC users report no significant change in libido although in most studies a decline in plasma levels of free testosterone and an increase in those of sex hormone binding globulin were observed.

  11. Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Okita Yoshihiro

    2010-02-01

    Full Text Available Abstract Background The combination of gemcitabine (GEM and S-1, an oral 5-fluorouracil (5-FU derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. Methods Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed. Results The maximum concentration (Cmax, the area under the curve from the drug administration to the infinite time (AUCinf, and the elimination half-life (T1/2 of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax were not significantly different between S-1 administration with and without GEM. Conclusion There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.

  12. Non-obese adult onset diabetes with oral hypoglycemic agent failure: islet cell autoantibodies or reversible beta cell refractoriness?

    Directory of Open Access Journals (Sweden)

    J.R. Sá

    2003-10-01

    Full Text Available Pancreatic ß cell function and insulin sensitivity, analyzed by the homeostasis model assessment, before and after 24 weeks of insulin therapy were studied and correlated with the presence of autoantibodies against ß cells (islet cell and anti-glutamic acid decarboxylase antibodies, in a group of 18 Brazilian lean adult non-insulin-dependent diabetes mellitus (NIDDM patients with oral hypoglycemic agent failure (OHAF. Median fasting plasma glucose before and after insulin treatment was 19.1 and 8.5 mmol/l, respectively (P < 0.001; median HbA1c was 11.7% before vs 7.2% after insulin treatment (P < 0.001. Forty-four percent of the patients were positive (Ab+ to at least one autoantibody. Fasting C-peptide levels were lower in Ab+ than Ab- patients, both before (Ab+: 0.16 ± 0.09 vs Ab-: 0.41 ± 0.35 nmol/l, P < 0.003 and after insulin treatment (Ab+: 0.22 ± 0.13 vs Ab-: 0.44 ± 0.24 nmol/l, P < 0.03. Improvement of Hß was seen in Ab- (median before: 7.3 vs after insulin therapy: 33.4%, P = 0.003 but not in Ab+ patients (median before: 6.6 vs after insulin therapy: 20.9%. These results show that the OHAF observed in the 18 NIDDM patients studied was due mainly to two major causes: autoantibodies and ß cell desensitization. Autoantibodies against ß cells could account for 44% of OHAF, but Ab- patients may still present ß cell function recovery, mainly after a period of ß cell rest with insulin therapy. However, the effects of ß cell function recovery on the restoration of the response to oral hypoglycemic agents need to be determined.

  13. Biodistribution study with combined administration of BPA and BSH for BNCT in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    Garabalino, M A; Heber, E M; Monti Hughes, A; Pzzi, E C C; Molinari, A J; Niggg, D W; Bauer, W; Trivillin, V A; Schwint, A E

    2012-01-01

    We previously proved the therapeutic potential of the chemically non-selective boron compound decahydrodecaborate (GB-10) as a stand-alone boron carrier for BNCT in the hamster cheek pouch oral cancer model with no toxic effects in normal or precancerous tissue. Although GB-10 is not taken up selectively by oral tumor tissue, selective tumor lethality would result from selective aberrant tumor blood vessel damage. Furthermore, BNCT efficacy was enhanced when GB-10 and boronophenylalanine (BPA) were administered jointly. The fact that sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically as a stand-alone boron agent for BNCT of brain tumors and in combination with BPA for recurrent head and neck malignancies makes it a particularly interesting boron compound to explore. Based on the working hypothesis that BSH would conceivably behave similarly to GB-10 in oral cancer, we previously performed biodistribution studies with BSH alone in the hamster cheek pouch oral cancer model. The aim of the present study was to perform biodistribution studies of BSH + BPA administered jointly in the hamster cheek pouch oral cancer model as a starting point to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology and optimize therapeutic efficacy. The right cheek pouch of Syrian hamsters was subjected to topical administration of a carcinogen twice a week for 12 weeks. Once the exophytic tumors, i.e. squamous cell carcinomas, had developed, the animals were used for biodistribution studies with BSH + BPA. Three administration protocols with different proportions of each of the compounds were assessed: 1. BSH, 50 mg 10 B/kg, iv + BPA, 15.5 mg 10 B/kg, ip; 2. BSH, 34.5 mg 10 B/kg, iv + BPA, 31 mg 10 B/kg, ip; 3. BSH, 20 mg 10 B/kg, iv + BPA, 46.5 mg 10 B/kg, ip. Groups of animals were euthanized 4 h after the administration of BSH and 3 h after the administration of BPA. Samples of blood, tumor, precancerous and normal pouch and other tissues with

  14. Developing Optimal Combination of Bulking Agents in an In-Vessel Composting of Vegetable Waste

    Directory of Open Access Journals (Sweden)

    C. C. Monson

    2010-01-01

    Full Text Available The objective of the study is to determine the optimum combination of feed stock components for composting the organic solid waste, a prerequisite for effective microbial degradation and for obtaining quality compost. Combination of dry leaves with locally available bulking agents like sawdust, wood shavings, paddy straw, sugarcane bagasse and rice husk are composted along with vegetable waste in a laboratory scale reactor for the study. The central core of composting process is replicated in controlled conditions in the in-vessel by keeping initial feed stock C/N ratio fixed between 30 and 35. The study is monitored for 14 days for the variations in temperature, pH, moisture and macronutrients C and N of the compost. It is found that composting vegetable waste with the combination of paddy straw and dry leaves provided best results of C/N ratio of 17.58 confirming that, if right feedstock components are provided, an effective environment for the growth of microorganisms is achieved to accelerate the process to produce a resultant C/N ratio acceptable to be used as compost.

  15. KR-12-a5 is a non-cytotoxic agent with potent antimicrobial effects against oral pathogens.

    Science.gov (United States)

    Caiaffa, Karina Sampaio; Massunari, Loiane; Danelon, Marcelle; Abuna, Gabriel Flores; Bedran, Telma Blanca Lombardo; Santos-Filho, Norival Alves; Spolidorio, Denise Madalena Palomari; Vizoto, Natalia Leal; Cilli, Eduardo Maffud; Duque, Cristiane

    2017-11-01

    This study evaluated the cytotoxicity and antimicrobial activity of analogs of cationic peptides against microorganisms associated with endodontic infections. L-929 fibroblasts were exposed to LL-37, KR-12-a5 and hBD-3-1C V and chlorhexidine (CHX, control), and cell metabolism was evaluated with MTT. The minimal inhibitory concentration (MIC) and the minimal bactericidal/fungicidal concentration (MBC/MFC) of the peptides and CHX were determined against oral pathogens associated with endodontic infections. Enterococcus faecalis and Streptococcus mutans biofilms were cultivated in bovine dentin blocks, exposed to different concentrations of the most efficient antimicrobial peptide and analyzed by confocal laser scanning microscopy. CHX and peptides affected the metabolism of L-929 at concentrations > 31.25 and 500 μg ml -1 , respectively. Among the peptides, KR-12-a5 inhibited growth of both the microorganisms tested with the lowest MIC/MBC/MFC values. In addition, KR-12-a5 significantly reduced E. faecalis and S. mutans biofilms inside dentin tubules. In conclusion, KR-12-a5 is a non-cytotoxic agent with potent antimicrobial and anti-biofilm activity against oral pathogens associated with endodontic infections.

  16. Influence of Mycotoxins and a Mycotoxin Adsorbing Agent on the Oral Bioavailability of Commonly Used Antibiotics in Pigs

    Directory of Open Access Journals (Sweden)

    Siska Croubels

    2012-04-01

    Full Text Available It is recognized that mycotoxins can cause a variety of adverse health effects in animals, including altered gastrointestinal barrier function. It is the aim of the present study to determine whether mycotoxin-contaminated diets can alter the oral bioavailability of the antibiotics doxycycline and paromomycin in pigs, and whether a mycotoxin adsorbing agent included into diets interacts with those antibiotics. Experiments were conducted with pigs utilizing diets that contained blank feed, mycotoxin-contaminated feed (T-2 toxin or deoxynivalenol, mycotoxin-contaminated feed supplemented with a glucomannan mycotoxin binder, or blank feed supplemented with mycotoxin binder. Diets with T-2 toxin and binder or deoxynivalenol and binder induced increased plasma concentrations of doxycycline administered as single bolus in pigs compared to diets containing blank feed. These results suggest that complex interactions may occur between mycotoxins, mycotoxin binders, and antibiotics which could alter antibiotic bioavailability. This could have consequences for animal toxicity, withdrawal time for oral antibiotics, or public health.

  17. Evaluation of tumor invasion in gastric carcinoma with CT using water as an oral contrast agent in prone position

    International Nuclear Information System (INIS)

    Chung, Jin Il; Lee, Jong Tae; Yoo, Hyung Sik; Lee, Byung Hee; Bae, Jong Yup

    1994-01-01

    To evaluate the accuracy of CT using water as an oral contrast material in a prone position in determining the depth of tumor invasion in gastric cancer patients. Thirty three patients(19 male, 14 female) with surgically confirmed gastric cancer were studied. We performed CT in a prone position after ingestion of 1 liter of pure water. CT findings were classified into 4 groups by the morphologic appearance of infiltrates in the perigastric fat plane: normal perigastric fat(S0), fine mottled densities(S1), irregular aggregated or liner densities(S2) and direct extension and invasion of tumor into contiguous structures(S3). Also we prospectively compared the CT staging with pathologic T staging according to the TNM systems. The overall accuracy of CT staging in determining the pathologic T factor was 69.6%. As we regarded T1 and T2 lesions as one group on CT, the accuracy of CT staging was increased to 80.2% because of a limitation of CT for distinguishing T1 from T2 lesions. Prone position CT using water as an oral contrast agent is quite accurate in determining the T staging of gastric carcinoma

  18. Novel liposomal combination treatments using dual genes knockdown in oral cancer treatment

    Science.gov (United States)

    Wu, Jyun-Sian; Yeh, Chia-Hsien; Huang, Leaf; Hsu, Yih-Chih

    2018-02-01

    Small interfering RNA (siRNA) can be used to treat tumor because it can effectively knockdown target oncoprotein expression and it leads to cancer cell death and apoptosis. Hypoxia-inducible factors-1 (HIF-1) is a transcription factor gene. Its high expression of tumor hypoxia cells, activation of transcription factor HIF-1α and angiogenesis found in most cancerous tissues. HIF-1α protein in cancer cells are critical to cell survival, tumor growth and proliferation. Epidermal growth factor receptor (EGFR) gene is another common head and neck oncogene. The dual self-designed siRNA sequences were encapsulated in the lipid-calcium-phosphate (LCP) and targeted to sigma receptors on the surface of cancer cells via binding to amino ethyl anisamide (AEAA). We used human oral cancer cells to establish the xenograft animal model to study the combination therapy for therapeutic results.

  19. Immunological effects of Sizofiran (SPG) combined with irradiation in patients with oral cancer

    International Nuclear Information System (INIS)

    Tominaga, Kazuhiro; Tominaga, Naohiro; Tokuhisa, Michio

    1995-01-01

    Effects of Sizofiran (SPG) combined with irradiation for primary oral squamous cell carcinoma were evaluated with regard to cell-mediated immunity. Twenty-four patients, who were managed with irradiation from 1989 to 1993, were divided into two groups, a SPG group and a control group. Thirteen patients received concomitant administration of SPG intramuscularly with irradiation as SPG group, and 11 patients were not administered any biological response modifiers as the control group. In the SPG group, depression of blastoid transformation of lymphocytes, IL-2 production and LAK activity due to irradiation were prevented, and recovery of blastoid transformation was promoted, while peripheral monocytes tended to increase. Upon comparison for survival (Kaplan-Meier method) between the SPG group and control group, the survival rate of the SPG group tended to be superior to that of the control group. However, no significant difference was observed between them. (author)

  20. Knowledge of users of low-dose oral combined contraceptives about the method

    Directory of Open Access Journals (Sweden)

    Camila Félix Américo

    2013-07-01

    Full Text Available OBJECTIVES: to identify the knowledge of users of combined oral contraceptive about correct use, side effects and complications; to verify the correlation between knowledge about the method with age, education, family income and time of use. METHOD: cross-sectional study performed in Fortaleza, Ceará, Brazil, from March to July 2010, with 294 women. Data were collected through interviews. RESULTS: 75% had substantial knowledge about the proper use and side effects and no knowledge about complications. The higher the educational level and family income, the higher the women's knowledge about the correct use of the method. Positive correlation suggests that women who used the method for longer knew more about its side effects. CONCLUSION: there are knowledge gaps about the method, which are influenced by socioeconomic variables and use time.

  1. Love-Wave Sensors Combined with Microfluidics for Fast Detection of Biological Warfare Agents

    Directory of Open Access Journals (Sweden)

    Daniel Matatagui

    2014-07-01

    Full Text Available The following paper examines a time-efficient method for detecting biological warfare agents (BWAs. The method is based on a system of a Love-wave immunosensor combined with a microfluidic chip which detects BWA samples in a dynamic mode. In this way a continuous flow-through of the sample is created, promoting the reaction between antigen and antibody and allowing a fast detection of the BWAs. In order to prove this method, static and dynamic modes have been simulated and different concentrations of BWA simulants have been tested with two immunoreactions: phage M13 has been detected using the mouse monoclonal antibody anti-M13 (AM13, and the rabbit immunoglobulin (Rabbit IgG has been detected using the polyclonal antibody goat anti-rabbit (GAR. Finally, different concentrations of each BWA simulants have been detected with a fast response time and a desirable level of discrimination among them has been achieved.

  2. Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents

    DEFF Research Database (Denmark)

    Klose, Marianne; Lange, Martin; Rasmussen, Aase Krogh

    2007-01-01

    -hormone levels; corticosteroid-binding globulin levels; and test conditions (fasting/nonfasting, rest/intermittent exercise). METHODS: A 250-microg ACTH test (0800-1000 h) was performed in 100 unmedicated subjects, 13 women taking oral contraception (OC), and six men with nephrotic syndrome. Tests were performed...... fasting supine (n=119), nonfasting supine (n=38), and fasting with intermittent exercise (n=45). Serum cortisol was analyzed by three immunoassays. RESULTS: Even with a negligible between-assay mean bias, individual samples from unmedicated subjects differed by as much as 110 nmol/liter. The normative 2......-binding globulin, fasting/nonfasting, and exercise. Compared with unmedicated subjects, OC women had 2-fold elevated 30-min cortisol (P

  3. Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats.

    Science.gov (United States)

    Porters, N; de Rooster, H; Bosmans, T; Baert, K; Cherlet, M; Croubels, S; De Backer, P; Polis, I

    2015-04-01

    Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40 μg/kg) and buprenorphine (20 μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry. Plasma concentration-time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration-time curve (AUC) and the maximum plasma concentrations (Cmax ) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site. © 2014 John Wiley & Sons Ltd.

  4. Pharmacokinetics of dexmedetomidine combined with methadone following oral-transmucosal and intramuscular administration in dogs

    Directory of Open Access Journals (Sweden)

    Federica Di Cesare

    2017-05-01

    Full Text Available Oral-transmucosal (OTM drug delivery refers to noninvasive and painless administration of medical preparations through any oral cavity membrane to achieve systemic effects (Sattar et al., 2014. Regarding sedative drugs, OTM administration is very attractive in veterinary medicine, especially for patients difficult to inject and restrain (Messenger et al., 2016. This study aims to compare the pharmacokinetics of dexmedetomidine after OTM and intramuscular (IM administration combined with methadone. After obtaining Ethical Committee approval and owner’s written consent, eight dogs, were administered with dexmedetomidine (10 mg/kg and methadone (0.4 mg/kg by OTM and other 4 dogs by IM route. Blood samples were collected at prefixed times up to four hours. Dexmedetomidine was quantified by a validated HPLC-MS method. On dexmedetomidine concentrations, a pharmacokinetic analysis was carried out with a noncompartmental approach (Phoenix WinNonlin® 7.0, Pharsight, Cary, NC. Mean ± SD terminal half-lives of dexmedetomidine were 187.42 ± 109.66 and 94.78 ± 34.08 min after OTM and IM administration, respectively. Maximum serum (Cmax concentrations were 0.83 ± 0.32 and 9.09 ± 2.46 ng/mL for OTM and IM administration, respectively. Time to maximum concentration (Tmax were 44.38 ± 32.16 and 21.25±11.39 min by OTM and IM administration, respectively. Area under the curve from 0 to the last measured concentration (AUClast were 103.75 ± 30.23 and 614.87 ± 77.15 min*ng/mL for OTM and IM administration, respectively. Cmax, Tmax and AUClast values by OTM route demonstrate a lower and delayed absorption of the drug compared to IM. To complete the study, the pharmacokinetic analysis of methadone is foreseen, so as a clinical trial to compare the clinical effects of the combination of dexmedetomidine and methadone by OTM and IM administration and to establish an effective dosage of oral-transumucosal route in dogs for this association.

  5. An artemisinin derivative of praziquantel as an orally active antischistosomal agent.

    Directory of Open Access Journals (Sweden)

    Lanlan Dong

    Full Text Available Schistosomiasis is a major health problem in tropical and sub-tropical areas caused by species of trematode belonging to the genus Schistosoma. The treatment and control of this disease has been relying on the use of a single drug praziquantel. However, the drug resistance concern urged the development of new drugs against schistosoma. Here, we report our systematic biological evaluation of DW-3-15, a new lead compound developed based on our conjugation design rationale as an effective anti-schistosomal agent.The antischistosomal activity of DW-3-15 was systematically evaluated in S. japonicum infected mouse model for its stage-sensitivity and dose response. The results revealed that DW-3-15 exhibited 60-85% worm reduction rate against different development stage of worm. Scanning electron microscopy (SEM observation indicated that DW-3-15 may damage to the tegument of male schistosomes.Our results demonstrated that DW-3-15 showed potent anti-schistosomal activities in vivo. The results strongly support our conjugation design strategy of artemisinin analogs and further development of DW-3-15 as a new lead compound as anti-schistosomal agent.

  6. Effect of MR contrast agents on quantitative accuracy of PET in combined whole-body PET/MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lois, Cristina [University of Santiago de Compostela, Department of Particle Physics, Santiago de Compostela (Spain); Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela (Spain); Imaging Science Institute, Tuebingen (Germany); Bezrukov, Ilja [Eberhard Karls University, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens Foundation, Department of Preclinical Imaging and Radiopharmacy, Tuebingen (Germany); Max Plank Institute for Intelligent Systems, Department of Empirical Inference, Tuebingen (Germany); Schmidt, Holger [Eberhard Karls University, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens Foundation, Department of Preclinical Imaging and Radiopharmacy, Tuebingen (Germany); Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Schwenzer, Nina; Werner, Matthias K. [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Kupferschlaeger, Juergen [Eberhard Karls University, Nuclear Medicine, Department of Radiology, Tuebingen (Germany); Beyer, Thomas [Imaging Science Institute, Tuebingen (Germany); cmi-experts GmbH, Zuerich (Switzerland)

    2012-11-15

    Clinical PET/MR acquisition protocols entail the use of MR contrast agents (MRCA) that could potentially affect PET quantification following MR-based attenuation correction (AC). We assessed the effect of oral and intravenous (IV) MRCA on PET quantification in PET/MR imaging. We employed two MRCA: Lumirem {sup registered} (oral) and Gadovist {sup registered} (IV). First, we determined their reference PET attenuation values using a PET transmission scan (ECAT-EXACT HR+, Siemens) and a CT scan (PET/CT Biograph 16 HI-REZ, Siemens). Second, we evaluated the attenuation of PET signals in the presence of MRCA. Phantoms were filled with clinically relevant concentrations of MRCA in a background of water and {sup 18}F-fluoride, and imaged using a PET/CT scanner (Biograph 16 HI-REZ, Siemens) and a PET/MR scanner (Biograph mMR, Siemens). Third, we investigated the effect of clinically relevant volumes of MRCA on MR-based AC using human pilot data: a patient study employing Gadovist {sup registered} (IV) and a volunteer study employing two different oral MRCA (Lumirem {sup registered} and pineapple juice). MR-based attenuation maps were calculated following Dixon-based fat-water segmentation and an external atlas-based and pattern recognition (AT and PR) algorithm. IV and oral MRCA in clinically relevant concentrations were found to have PET attenuation values similar to those of water. The phantom experiments showed that under clinical conditions IV and oral MRCA did not yield additional attenuation of PET emission signals. Patient scans showed that PET attenuation maps are not biased after the administration of IV MRCA but may be biased, however, after ingestion of iron oxide-based oral MRCA when segmentation-based AC algorithms are used. Alternative AC algorithms, such as AT and PR, or alternative oral contrast agents, such as pineapple juice, can yield unbiased attenuation maps. In clinical PET/MR scenarios MRCA are not expected to lead to markedly increased attenuation

  7. Optimization of therapy of type 2 diabetes mellitus with the oral hypoglycemic agent glimepiride

    Directory of Open Access Journals (Sweden)

    Tatiana Ivanovna Romantsova

    2010-03-01

    Full Text Available Type 2 diabetes is believed to develop as a result of lowered insulin secretion and insulin resistance leading to hyperglycemia. Sulfonylureas stimulateinsulin secretion and thereby decrease blood glucose level which accounts for their wide application in the treatment of diabetes. However, manyagents of this class produce side effects (increased body mass, hypoglycemia, resistance to therapy, etc. attributable to excess stimulation of insulinsecretion. Glimepiride is as efficient as traditionally used sulfonylureas but causes a smaller rise in insulin secretion. Sulfonylurea receptors showlower affinity for glimepiride than for glibenclamide. Formation and dissociation of glimepiride-receptor complexes occur faster than those of glibenclamide-receptor complexes. In addition, therapeutic effect of glimepiride was shown to be associated with improved insulin sensitivity. It is concludedthat glimepiride is an efficacious agent for the treatment of type 2 diabetes.

  8. ·The clinical and biochemical effects of two combination oral ...

    African Journals Online (AJOL)

    1991-04-06

    Apr 6, 1991 ... ~a e . ~Iternately to use a monophasic oral contraceptive. ~ntalnlng 30 J.Lg ethinyloestradiol and 150 ",g desogestrel fn a!:oelon, group.A), or a triphasic oral contraceptive contain-. T ... hpoprotein p~ttern indUCed by oral contraceptives cause ... triphasic preparation), except that current cigarette smokers (5.

  9. Efficacy, safety, and patient acceptability of the combined chlormadinone acetate-ethinylestradiol oral contraceptive

    Directory of Open Access Journals (Sweden)

    Serena Ferrari

    2010-09-01

    Full Text Available Serena Ferrari, Marianna Cannoletta, Matteo Generali, Lucia Cazzato, Angelo CagnacciDepartment of Obstetrics, Gynecology, and Pediatrics, Azienda Ospedaliero, Universitaria di Modena, ItalyAbstract: Since their introduction in 1959, development of hormonal contraceptives has been ongoing, with the ultimate aim of creating not only an effective and safe contraceptive method, but also a drug able to meet the need for treatment of other conditions, such as acne, seborrhea, and hirsutism, with few or no side effects. With this objective, a new progestin, chlormadinone acetate (CMA, has been developed as a derivative of progesterone for ­contraception. This new molecule has been introduced in combination with ethinylestradiol (EE 30 µg as a safe ­contraceptive with antiandrogenic properties. Many clinical studies have investigated this new oral combination and found it to be safe, with a Pearl Index similar to that of other combined hormonal contraceptives. CMA, because of its antiandrogenic properties, has been also considered effective for resolution of acne, seborrhea, and hirsutism. The data show it to be a safe molecule in terms of glucose and lipid metabolism. No major weight changes have been linked with its use, and it seems to be the only progestin able to reduce fat mass during use. The CMA-EE combination is well tolerated and acceptable to women. Adverse events related to its use are similar to those reported with other third-generation ­contraceptives. We can conclude that CMA-EE is an effective, safe, and well tolerated ­antiandrogenic hormonal contraceptive.Keywords: chlormadinone acetate, acne, weight, metabolism, safety, hormonal contraceptive

  10. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease.

    Science.gov (United States)

    Weng, Yunqi; Yao, Jian; Sparks, Sawyer; Wang, Kevin Yueju

    2017-02-28

    Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK), a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, is produced by the bacterium Bacillus subtilis during the fermentation of soybeans to produce Natto. NK has been extensively studied in Japan, Korea, and China. Recently, the fibrinolytic (anti-clotting) capacity of NK has been recognized by Western medicine. The National Science Foundation in the United States has investigated and evaluated the safety of NK. NK is currently undergoing a clinical trial study (Phase II) in the USA for atherothrombotic prevention. Multiple NK genes have been cloned, characterized, and produced in various expression system studies. Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications. This review covers the history, benefit, safety, and production of NK. Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed.

  11. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Yunqi Weng

    2017-02-01

    Full Text Available Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK, a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, is produced by the bacterium Bacillus subtilis during the fermentation of soybeans to produce Natto. NK has been extensively studied in Japan, Korea, and China. Recently, the fibrinolytic (anti-clotting capacity of NK has been recognized by Western medicine. The National Science Foundation in the United States has investigated and evaluated the safety of NK. NK is currently undergoing a clinical trial study (Phase II in the USA for atherothrombotic prevention. Multiple NK genes have been cloned, characterized, and produced in various expression system studies. Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications. This review covers the history, benefit, safety, and production of NK. Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed.

  12. Role of oral hypoglycemic agents in the management of type 2 diabetes mellitus during Ramadan

    Directory of Open Access Journals (Sweden)

    Mir Iftikhar Bashir

    2012-01-01

    Full Text Available It is obligatory for all adult Muslims to observe fast during the holy month of Ramadan, but sick individuals including those with diabetes mellitus are exempted from the duty of fasting. Specific medical advice must be provided to individual patients concerning the potential risks they must accept if they decide to fast. Any alteration in medications deemed necessary to provide an effective and safe antidiabetic regimen should be instituted well before the start of Ramadan. Diet-controlled patients and those well controlled on insulin sensitizers have low risk of hypoglycemia and may safely fast with some modification in the timing of the doses. Newer generation sulfonylureas (gliclazide MR and glimepiride have reasonable safety profile during Ramadan fasting and are economical options for a large number of diabetics worldwide, especially in the developing countries; older, long acting sulfonylureas like glibenclamide and chlorpropamide should be avoided during fasting. Oral DPP-IV inhibitors are important substitutes to sulfonylureas for patients with diabetes mellitus during fasting owing to their glucose-dependent mechanism of action, efficacy, and tolerability. This group of drugs causes a moderate A1c reduction, are weight neutral, and have a very low risk of hypoglycemia. Short-acting insulin secretagogues are an option in the subset of fasting diabetic patients who have predominantly post-prandial hyperglycemia.

  13. Role of oral hypoglycemic agents in the management of type 2 diabetes mellitus during Ramadan

    Science.gov (United States)

    Bashir, Mir Iftikhar; Pathan, Md Faruque; Raza, Syed Abbas; Ahmad, Jamal; Khan, A. K. Azad; Ishtiaq, Osama; Sahay, Rakesh K.; Sheikh, Aisha; Zargar, Abdul Hamid

    2012-01-01

    It is obligatory for all adult Muslims to observe fast during the holy month of Ramadan, but sick individuals including those with diabetes mellitus are exempted from the duty of fasting. Specific medical advice must be provided to individual patients concerning the potential risks they must accept if they decide to fast. Any alteration in medications deemed necessary to provide an effective and safe antidiabetic regimen should be instituted well before the start of Ramadan. Diet-controlled patients and those well controlled on insulin sensitizers have low risk of hypoglycemia and may safely fast with some modification in the timing of the doses. Newer generation sulfonylureas (gliclazide MR and glimepiride) have reasonable safety profile during Ramadan fasting and are economical options for a large number of diabetics worldwide, especially in the developing countries; older, long acting sulfonylureas like glibenclamide and chlorpropamide should be avoided during fasting. Oral DPP-IV inhibitors are important substitutes to sulfonylureas for patients with diabetes mellitus during fasting owing to their glucose-dependent mechanism of action, efficacy, and tolerability. This group of drugs causes a moderate A1c reduction, are weight neutral, and have a very low risk of hypoglycemia. Short-acting insulin secretagogues are an option in the subset of fasting diabetic patients who have predominantly post-prandial hyperglycemia. PMID:22837904

  14. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

    NARCIS (Netherlands)

    Vos, Rimke C; van Avendonk, Mariëlle JP; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy EHM

    2016-01-01

    BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of

  15. The effects of combined treatment with radiation and bleomycin on the oral carcinoma involving the mandible

    International Nuclear Information System (INIS)

    Okamoto, Manabu; Ozeki, Satoru; Higuchi, Yoshinori; Tashiro, Hideo

    1988-01-01

    The effect of concurrent combined treatment with 22.5 Gy of radiation and 110 mg of bleomycin or 55 mg of peplomycin on oral carcinoma involving the mandible was examined histologically. In 14 of 18 patients who had mandibles resected after this combined treatment, bone invasion by carcinoma was observed histologically. According to Shimosato's classification of histological effects, 3 belonged to Grade III/IV, 4 to IIb, 3 to IIa and 4 to I. The formation of new bone that was considered to be reparable was observed in the marked effective patients. In 4 patients the Grade IIb, residual surviving cancer cells were observed in the mandible. Accordingly, excision was needed in the area of radiologic features of mandibular infiltration. But it is considered that although the excision scope for the patient who has received the preoperative treatment is the same as that for the patient who has not, it is advantageous for the former patient that a wider safety region is obtained. (author)

  16. Effects of combinations of maternal agents on the fetal cerebrum in rat

    International Nuclear Information System (INIS)

    Tanaka, Harumi; Iwasaki, Setsuo; Arima, Masataka; Nakazawa, Kazuharu

    1985-01-01

    Fetal cerebral development influenced by maternal ethanol or caffeine either singly or in combination with X-irradiation was investigated in rat. Female Wistar rats were given 20 % ethanol, 0.04 % caffeine and water during the premating period and pregnancy, and 0.03 % vitamin E only during pregnancy. Pregnant rats were X-irradiated with 100 R or sham-irradiated on gestational day 13. Ethanol-treatment alone much reduced the fetal body and cerebral weights, and X-irradiation alone resulted in great reductions in weight and DNA concentration in the fetal cerebrum. The reduction in body weight with ethanol exceeded that with X-irradiation, therefore, the addition of X-irradiation had no effect on that of ethanol. The reduction in cerebral weight on X-irradiation exceeded that with ethanol, thus the addition of ethanol had only a slight effect on that with X-irradiation. The decrease in body and cerebral weights and the increase in lipid peroxide (LP) formation on caffeine-treatment and the decrease in cerebral weight and the increase in LP on vitamin E-treatment were inhibited by X-irradiation as compared to the combined effects of the other drink treatments. The increase in placental weight and the decrease in cerebral weight on ethanol-treatment and the decrease in placental, body and cerebral weights on caffeine-treatment, which findings were covered by the addition of X-irradiation, became much clearer on single drink treatment. Independently of X-irradiation, ethanol-treatment resulted in increased fetal mortality and LP, and decreased body weight. These results suggest that the combined effects of maternal agents on live fetuses should be investigated as to whether they act independently of or dependently with each other and how the effects appear either singly or mixed. (author)

  17. Combined effect of genetic polymorphisms of AURKA and environmental factors on oral cancer development in Taiwan.

    Directory of Open Access Journals (Sweden)

    Chia-Hsuan Chou

    Full Text Available Oral squamous cell carcinoma (OSCC is the sixth and fourth most common cause of cancer death in men worldwide and in Taiwan, respectively. AURKA, which encodes a centrosome-related serine/threonine kinase, is frequently amplified and overexpressed in many human cancers, particularly advanced OSCC. We conducted a hospital-based case-control study to estimate AURKA single-nucleotide polymorphisms (SNPs and environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics.We enrolled a total of 876 OSCC patients and 1200 controls. Four SNPs of AURKA, namely rs1047972, rs2273535, rs2064863, and rs6024836, were analyzed using real-time polymerase chain reaction (PCR. Among the 1420 smokers, the AURKA polymorphism carriers with the betel nut chewing habit had a higher risk of oral cancer than AURKA wild-type (WT carriers without the betel nut chewing habit. Patients with the AURKA rs2064863 gene had a 1.365-fold higher risk of stage III or IV OSCC (95% confidence interval [CI] 1.029-1.811 than those with the rs2064863 WT gene. Furthermore, carriers of the AURKA rs1047972/rs2273535/rs2064863 C-A-T haplotype had a 1.736-fold (95% CI 1.110-2.715 higher risk of OSCC than controls (C-T-T, the most common haplotype. Among patients with the betel quid chewing habit, carriers of other haplotypes (C-T-T, C-A-G, T-A-T, T-A-G, T-T-T, and C-T-G had a 12.857-fold (95% CI 10.731-15.404 increased risk, and carriers of the C-A-T haplotype had the highest risk (AOR: 31.120; 95% CI 13.864-69.850 of OSCC, compared with those without the betel quid chewing who harbored other haplotypes.In conclusion, betel nut chewing combined with the AURKA C-A-T haplotypes lead to a high risk of OSCC. These findings reveal a novel genetic-environmental predisposition for oral tumorigenesis.

  18. Radiopotentiation by the oral platinum agent, JM216: role of repair inhibition

    International Nuclear Information System (INIS)

    Amorino, George P.; Freeman, Michael L.; Carbone, David P.; Lebwohl, David E.; Choy, Hak

    1999-01-01

    Purpose: To test for in vitro radiopotentiation by the orally-administered platinum (IV) complex, JM216; to compare these results to cisplatin and carboplatin; and to investigate whether the mechanism of radiopotentiation involves repair inhibition of radiation-induced DNA damage. Methods and Materials: H460 human lung carcinoma cells were incubated with the drugs for 1 h at 37 deg. C, irradiated at room temperature, and returned to 37 deg. C for 20 min. Cells were then rinsed and colony forming ability was assessed. Wild-type V79 Chinese hamster cells and radiosensitive, DNA repair-deficient mutant cells (XR-V15B) were also studied along with H460 cells. Ku86 cDNA, which encodes part of a protein involved in DNA repair, was transfected into XR-V15B cells as previously described. The effect of JM216 on sublethal damage repair (SLDR) was also assessed using split-dose recovery. Results: Using equally cytotoxic doses of JM216, cisplatin, and carboplatin, the radiation dose enhancement ratios (DER) were 1.39, 1.31, and 1.20, respectively; the DER with 20 μM JM216 was 1.57. JM216 (20 μM) did not significantly change the final slope of radiation survival curves, but greatly reduced the survival curve shoulder. V79 cells also showed radioenhancement using 20 μM JM216, but no enhancement occurred using XR-V15B cells. Transfection of Ku86 cDNA into XR-V15B cells restored radiopotentiation by JM216 to wild-type V79 levels. In addition, 20 μM JM216 completely inhibited sublethal damage repair in H460 cells. Conclusion: Our results show that JM216 can potentiate the effects of radiation in human lung cancer cells, and that the mechanism of this effect is probably inhibition of DNA repair by JM216

  19. Oral contrast agents for small bowel MRI: comparison of different additives to optimize bowel distension

    Energy Technology Data Exchange (ETDEWEB)

    Ajaj, Waleed; Goehde, Susanne C.; Ruehm, Stefan G.; Debatin, Joerg F.; Lauenstein, Thomas C. [Department of Diagnostic and Interventional Radiology, University Hospital Essen, Hufelandstrasse 55, 45122, Essen (Germany); Schneemann, Hubert [Institute of Pharmacy and Pharmaceutical Sciences, University Hospital Essen, Essen (Germany)

    2004-03-01

    The purpose of this study was to compare two osmotic carbohydrate sugar alcohols (mannitol 2.5% and sorbitol 2.5%, 2.0%, and 1.5% watery solutions) in combination with 0.2% locust bean gum (LBG) for small bowel distension for MR imaging. Small bowel distension was quantified on coronal 2D TrueFISP images by measuring the diameters of 16 small bowel loops in each of 12 healthy subjects (age range 31-55 years). Additionally, the grade of small bowel distension was rated qualitatively. Patient acceptance concerning nausea, vomiting, flatulence, and diarrhea was noted for each solution, and all results were compared by a Wilcoxon test or t test, respectively. The ingestion of water combined with LBG and either 2.5% mannitol or 2.0% sorbitol showed the best distension of the small bowel. The lowest side effect rate was observed following ingestion of sorbitol in a concentration of 2.0 and 1.5%. Based on these data, we recommend a combination of LBG and 2% sorbitol use for optimal bowel distension and minimal side effects resulting in enhanced patient acceptance. (orig.)

  20. Oral contrast agents for small bowel MRI: comparison of different additives to optimize bowel distension

    International Nuclear Information System (INIS)

    Ajaj, Waleed; Goehde, Susanne C.; Ruehm, Stefan G.; Debatin, Joerg F.; Lauenstein, Thomas C.; Schneemann, Hubert

    2004-01-01

    The purpose of this study was to compare two osmotic carbohydrate sugar alcohols (mannitol 2.5% and sorbitol 2.5%, 2.0%, and 1.5% watery solutions) in combination with 0.2% locust bean gum (LBG) for small bowel distension for MR imaging. Small bowel distension was quantified on coronal 2D TrueFISP images by measuring the diameters of 16 small bowel loops in each of 12 healthy subjects (age range 31-55 years). Additionally, the grade of small bowel distension was rated qualitatively. Patient acceptance concerning nausea, vomiting, flatulence, and diarrhea was noted for each solution, and all results were compared by a Wilcoxon test or t test, respectively. The ingestion of water combined with LBG and either 2.5% mannitol or 2.0% sorbitol showed the best distension of the small bowel. The lowest side effect rate was observed following ingestion of sorbitol in a concentration of 2.0 and 1.5%. Based on these data, we recommend a combination of LBG and 2% sorbitol use for optimal bowel distension and minimal side effects resulting in enhanced patient acceptance. (orig.)

  1. Shifting to a non-vitamin K antagonist oral anticoagulation agent from vitamin K antagonist in atrial fibrillation.

    Science.gov (United States)

    Fosbøl, Emil L; Vinding, Naja Emborg; Lamberts, Morten; Staerk, Laila; Gundlund, Anna; Gadsbøll, Kasper; Køber, Lars; Gislason, Gunnar H; Olesen, Jonas Bjerring

    2017-06-28

    After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran, rivaroxaban, or apixaban) has not been quantified, and could help assess whether these drugs are used according to recommendations. Using Danish nationwide registries, we identified all VKA-experienced NVAF patients initiating a NOAC from 22 August 2011 to 31 December 2015 (shifters) and all VKA-experienced NVAF patients who were not switched to NOACs (non-shifters). Baseline characteristics and temporal utilization trends were examined. We included 62 065 patients with NVAF; of these, 19 386 (29.6%) shifted from a VKA to a NOAC (9973 (54.2%) shifted to dabigatran, 4775 (26.0%) to rivaroxaban, and 3638 (19.8%) to apixaban). Shifting was associated with lower age [odds ratio (OR) 0.95, 95% confidence interval (95% CI) 0.94-0.96 per 5 year increments], female gender (OR 1.33, 95% CI 1.28-1.38), and certain co-morbidities: more often stroke, bleeding, heart failure, and alcohol abuse, and less often hypertension, ischaemic heart disease, and diabetes. Shifting was common and initially dominated by shifting from VKA to dabigatran, but at the end of 2015, most shifters were shifted to rivaroxaban (45%) or apixaban (45%) whereas shifting to dabigatran decreased (to 10%). In a contemporary setting among VKA-experienced NVAF patients; VKA is still prevalent although about 30% by December 2015 had shifted to a NOAC. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  2. Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials

    OpenAIRE

    Andrew S Holpuch; Kashappa-Goud H Desai; Steven P Schwendeman; Susan R Mallery

    2011-01-01

    Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have as...

  3. In-hospital mortality after pre-treatment with antiplatelet agents or oral anticoagulants and hematoma evacuation of intracerebral hematomas.

    Science.gov (United States)

    Stein, Marco; Misselwitz, Björn; Hamann, Gerhard F; Kolodziej, Malgorzata; Reinges, Marcus H T; Uhl, Eberhard

    2016-04-01

    Pre-treatment with antiplatelet agents is described to be a risk factor for mortality after spontaneous intracerebral hemorrhage (ICH). However, the impact of antithrombotic agents on mortality in patients who undergo hematoma evacuation compared to conservatively treated patients with ICH remains controversial. This analysis is based on a prospective registry for quality assurance in stroke care in the State of Hesse, Germany. Patients' data were collected between January 2008 and December 2012. Only patients with the diagnosis of spontaneous ICH were included (International Classification of Diseases 10th Revision codes I61.0-I61.9). Predictors of in-hospital mortality were determined by univariate analysis. Predictors with Phematoma evacuation (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.24-4.97; P=0.010) compared to patients without antiplatelet pre-treatment treatment (OR: 0.9; 95% CI: 0.79-1.09; P=0.376). In conclusion a higher rate of in-hospital mortality after pre-treatment with antiplatelet agents in combination with hematoma evacuation after spontaneous ICH was observed in the presented cohort. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Trade-off between synergy and efficacy in combinations of HIV-1 latency-reversing agents.

    Science.gov (United States)

    Gupta, Vipul; Dixit, Narendra M

    2018-02-01

    Eradicating HIV-1 infection is difficult because of the reservoir of latently infected cells that gets established soon after infection, remains hidden from antiretroviral drugs and host immune responses, and retains the capacity to reignite infection following the cessation of treatment. Drugs called latency-reversing agents (LRAs) are being developed to reactivate latently infected cells and render them susceptible to viral cytopathicity or immune killing. Whereas individual LRAs have failed to induce adequate reactivation, pairs of LRAs have been identified recently that act synergistically and hugely increase reactivation levels compared to individual LRAs. The maximum synergy achievable with LRA pairs is of clinical importance, as it would allow latency-reversal with minimal drug exposure. Here, we employed stochastic simulations of HIV-1 transcription and translation in latently infected cells to estimate this maximum synergy. We incorporated the predominant mechanisms of action of the two most promising classes of LRAs, namely, protein kinase C agonists and histone deacetylase inhibitors, and quantified the activity of individual LRAs in the two classes by mapping our simulations to corresponding in vitro experiments. Without any adjustable parameters, our simulations then quantitatively captured experimental observations of latency-reversal when the LRAs were used in pairs. Performing simulations representing a wide range of drug concentrations, we estimated the maximum synergy achievable with these LRA pairs. Importantly, we found with all the LRA pairs we considered that concentrations yielding the maximum synergy did not yield the maximum latency-reversal. Increasing concentrations to increase latency-reversal compromised synergy, unravelling a trade-off between synergy and efficacy in LRA combinations. The maximum synergy realizable with LRA pairs would thus be restricted by the desired level of latency-reversal, a constrained optimum we elucidated with

  5. Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

    Science.gov (United States)

    Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

    2014-03-01

    The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

  6. Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism : a systematic review and meta-analysis

    NARCIS (Netherlands)

    van Vlijmen, E. F. W.; Wiewel-Verschueren, S.; Monster, T. B. M.; Meijer, K.

    Background Combined oral contraceptives (COCs) are associated with an increased risk of venous thromboembolism (VTE), which is shown to be more pronounced in women with hereditary thrombophilia. Currently, WHO recommendations state that COC-use in women with hereditary thrombophilias (antithrombin

  7. Effects of combined traditional Chinese medicine with immunosuppressive agents for patients with myasthenia gravis

    Science.gov (United States)

    Qi, Guoyan; Gu, Shanshan; Liu, Peng; Yang, Hongxia; Dong, Huimin

    2015-01-01

    Myasthenia gravis (MG) is a kind of autoimmune disease induced by transferring dysfunction of neuromuscular junction. In the present study, we developed an integrated therapy combined with traditional Chinese medicine and immuno suppressive agents to seek for an effective treatment of MG. 220 MG patients were randomly divided into two groups with different therapies. Plasma levels of acetylcholine receptors antibodies (AchRAb) and CD4+CD25+ regulatory T cells (CD4+CD25+Treg) were conducted through ELISA and flow cytometry. The amount of AchRAb (8.52±0.96 vs. 5.22±0.46) and CD4+CD25+Treg (1.94±1.21 vs. 3.21±0.96) in Group A receiving integrated therapy were significantly improved compared with Group B; the clinical performance of group treated with the integrated therapy was also much better. The integrated therapy in the present study could significantly improve the condition of MG with high recovery rate and low recurrence rate, which can be employed in future clinical treatment of MG. PMID:26770531

  8. Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians.

    Science.gov (United States)

    Nappi, Rossella E; Kaunitz, Andrew M; Bitzer, Johannes

    2016-01-01

    The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices.

  9. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control

    Directory of Open Access Journals (Sweden)

    Di Pierro F

    2012-07-01

    Full Text Available Francesco Di Pierro,1 Nicola Villanova,2 Federica Agostini,2 Rebecca Marzocchi,2 Valentina Soverini,2 Giulio Marchesini21Scientific Department, Velleja Research, Milano, 2Diseases of Metabolism, S Orsola Malpighi Hospital, Bologna, ItalyBackground: Suboptimal glycemic control is a common situation in diabetes, regardless of the wide range of drugs available to reach glycemic targets. Basic research in diabetes is endeavoring to identify new actives working as insulin savers, use of which could delay the introduction of injectable insulin or reduce the insulin dose needed. Commonly available as a nutraceutical, berberine is a potential candidate.Methods and results: Because its low oral bioavailability can be overcome by P-glycoprotein inhibitors like herbal polyphenols, we have tested the nutraceutical combination of Berberis aristata extract and Silybum marianum extract (Berberol® in type 2 diabetes in terms of its additive effect when combined with a conventional oral regimen for patients with suboptimal glycemic control. After 90 days of treatment, the nutraceutical association had a positive effect on glycemic and lipid parameters, significantly reducing glycosylated hemoglobin, basal insulin, homeostatic model assessment of insulin resistance, total and low-density lipoprotein cholesterol, and triglycerides. A relevant effect was also observed in terms of liver function by measuring aspartate transaminase and alanine transaminase. The product had a good safety profile, with distinctive gastrointestinal side effects likely due to its acarbose-like action.Conclusion: Although further studies should be carried out to confirm our data, Berberol could be considered a good candidate as an adjunctive treatment option in diabetes, especially in patients with suboptimal glycemic control.Keywords: berberine, silymarin, glycosylated hemoglobin, diabetes

  10. Activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus H-1

    International Nuclear Information System (INIS)

    Moehler, Markus; Sieben, Maike; Roth, Susanne; Springsguth, Franziska; Leuchs, Barbara; Zeidler, Maja; Dinsart, Christiane; Rommelaere, Jean; Galle, Peter R

    2011-01-01

    Parvovirus H-1 (H-1PV) infects and lyses human tumor cells including melanoma, hepatoma, gastric, colorectal, cervix and pancreatic cancers. We assessed whether the beneficial effects of chemotherapeutic agents or targeted agents could be combined with the oncolytic and immunostimmulatory properties of H-1PV. Using human ex vivo models we evaluated the biological and immunological effects of H-1PV-induced tumor cell lysis alone or in combination with chemotherapeutic or targeted agents in human melanoma cells +/- characterized human cytotoxic T-cells (CTL) and HLA-A2-restricted dendritic cells (DC). H-1PV-infected MZ7-Mel cells showed a clear reduction in cell viability of >50%, which appeared to occur primarily through apoptosis. This correlated with viral NS1 expression levels and was enhanced by combination with chemotherapeutic agents or sunitinib. Tumor cell preparations were phagocytosed by DC whose maturation was measured according to the treatment administered. Immature DC incubated with H-1PV-induced MZ7-Mel lysates significantly increased DC maturation compared with non-infected or necrotic MZ7-Mel cells. Tumor necrosis factor-α and interleukin-6 release was clearly increased by DC incubated with H-1PV-induced SK29-Mel tumor cell lysates (TCL) and was also high with DC-CTL co-cultures incubated with H-1PV-induced TCL. Similarly, DC co-cultures with TCL incubated with H-1PV combined with cytotoxic agents or sunitinib enhanced DC maturation to a greater extent than cytotoxic agents or sunitinib alone. Again, these combinations increased pro-inflammatory responses in DC-CTL co-cultures compared with chemotherapy or sunitinib alone. In our human models, chemotherapeutic or targeted agents did not only interfere with the pronounced immunomodulatory properties of H-1PV, but also reinforced drug-induced tumor cell killing. H-1PV combined with cisplatin, vincristine or sunitinib induced effective immunostimulation via a pronounced DC maturation, better cytokine

  11. Efficacy and Safety of Combined Oral and Enema Therapy Using Polyethylene Glycol 3350-Electrolyte for Disimpaction in Pediatric Constipation.

    Science.gov (United States)

    Yoo, Taeyeon; Bae, Sun Hwan

    2017-12-01

    We evaluated the efficacy and safety of combined oral and enema therapy using polyethylene glycol (PEG) 3350 with electrolyte solution for disimpaction in hospitalized children. We retrospectively studied 28 children having functional constipation who received inpatient treatment between 2008 and 2016. The amount of oral PEG 3350 electrolyte solution administered was 50-70 mL/kg/d (PEG 3350, 3-4.1 g/kg/d), and an enema solution was administered 1-2 times a day as a single dose of 15-25 mL/kg (PEG 3350, 0.975-1.625 g/kg/d). A colon transit time (CTT) test based on the Metcalf protocol was performed in some patients. Administration of oral and enema doses of PEG 3350 electrolyte solution showed 2.1±0.3 times and 2.9±0.4 times, respectively. After disimpaction, the frequency of defecation increased from 2.2±0.3 per week to once a day (1.1±0.1 per day). The number of patients who complained of abdominal pain was reduced from 15 (53.6%) to 4 (14.3%). Before hospitalization, nine patients underwent a CTT test, and 5 of 9 patients (55.6%) were classified as belonging to a group showing abnormalities. And in some patients, mild adverse effects were noted. We examined electrolytes and osmolality before and after disimpaction in 16 of 28 patients, and no abnormalities were noted. In terms of therapeutic efficacy and safety, combined oral and enema therapy using high-dose PEG 3350 with electrolytes is considered superior to conventional oral monotherapy or combined oral and enema therapy on an outpatient basis.

  12. Knowledge and attitudes of Latin American gynecologists regarding unplanned pregnancy and use of combined oral contraceptives

    Directory of Open Access Journals (Sweden)

    Bahamondes L

    2015-05-01

    Full Text Available Luis Bahamondes,1 Josefina Lira-Plasencia,2 Ricardo Martin,3 Victor Marin,4 Maria Y Makuch1 1Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas (UNICAMP, Campinas, Brazil; 2Instituto Nacional de Perinatología, México, DF, México; 3Hospital Universitario, Fundación Santa Fe de Bogotá, Bogotá, Colombia; 4Hospital Central, Petróleos Mexicanos, México, DF, México Background: Unintended pregnancy is a public health problem and unmet medical need worldwide. It is estimated that in the year 2012, almost 213 million pregnancies occurred, and the global pregnancy rate decreased only slightly from 2008 to 2012. It was also estimated that 85 million pregnancies (40% of all pregnancies were unintended and that 38% ended in an unintended birth. Objectives: To assess knowledge and attitudes of Latin American (LA obstetricians and gynecologists (OBGYNs regarding unintended pregnancies and aspects of combined oral contraceptive (COC use. Methods: A survey was conducted during a scientific meeting about contraception in 2014, in which OBGYNs from 12 LA countries who provide attention in contraception were invited to respond to a multiple-choice questionnaire to assess their knowledge and attitudes regarding unplanned pregnancy and some aspects regarding COC use. Results: A total of 210 OBGYNs participated in the study. Their knowledge regarding COC failure was low. The participants reported they believed that their patients habitually forgot to take a pill and that their patients did not know what to do in these situations. They were aware of the benefits of COC use; however, they were less prone to prescribe COCs for the purpose of protecting against ovarian and endometrial cancer, and one-quarter of them had doubts about the association between COC use and cancer risk. Conclusion: The interviewed LA OBGYNs showed some flaws in terms of knowledge of COC failure rates and the non-contraceptive benefits and risks

  13. Efficacy and Safety of Combined Oral and Enema Therapy Using Polyethylene Glycol 3350-Electrolyte for Disimpaction in Pediatric Constipation

    OpenAIRE

    Yoo, Taeyeon; Bae, Sun Hwan

    2017-01-01

    Purpose We evaluated the efficacy and safety of combined oral and enema therapy using polyethylene glycol (PEG) 3350 with electrolyte solution for disimpaction in hospitalized children. Methods We retrospectively studied 28 children having functional constipation who received inpatient treatment between 2008 and 2016. The amount of oral PEG 3350 electrolyte solution administered was 50–70 mL/kg/d (PEG 3350, 3–4.1 g/kg/d), and an enema solution was administered 1–2 times a day as a single dose...

  14. In vitro synergistic combinations of pentamidine, polymyxin B, tigecycline and tobramycin with antifungal agents against Fusarium spp.

    Science.gov (United States)

    Pozzebon Venturini, Tarcieli; Rossato, Luana; Chassot, Francieli; Tairine Keller, Jéssica; Baldissera Piasentin, Fernanda; Morais Santurio, Janio; Hartz Alves, Sydney

    2016-08-01

    The genus Fusarium is characterized by hyaline filamentous fungi that cause infections predominantly in immunocompromised patients. The remarkable primary resistance to antifungal agents of this genus requires a search for new therapeutic possibilities. This study assessed the in vitro susceptibility of 25 clinical isolates of Fusarium against antifungal agents (amphotericin B, caspofungin, itraconazole and voriconazole) and antimicrobials (pentamidine, polymyxin B, tigecycline and tobramycin) according to the broth microdilution method (M38-A2). The interactions between antifungal and antimicrobial agents were evaluated by the microdilution checkerboard method. Pentamidine and polymyxin B showed MIC values ≥4 µg ml-1 against Fusarium spp. The highest rates of synergism were observed when amphotericin B or voriconazole was combined with tobramycin (80 % and 76 %, respectively), polymyxin B (76 % and 64 %) and pentamidine (72 % and 68 %). The most significant combinations deserve in vivo evaluations in order to verify their potential in the treatment of fusariosis.

  15. Combination of Bifunctional Alkylating Agent and Arsenic Trioxide Synergistically Suppresses the Growth of Drug-Resistant Tumor Cells

    Directory of Open Access Journals (Sweden)

    Pei-Chih Lee

    2010-05-01

    Full Text Available Drug resistance is a crucial factor in the failure of cancer chemotherapy. In this study, we explored the effect of combining alkylating agents and arsenic trioxide (ATO on the suppression of tumor cells with inherited or acquired resistance to therapeutic agents. Our results showed that combining ATO and a synthetic derivative of 3a-aza-cyclopenta[a]indenes (BO-1012, a bifunctional alkylating agent causing DNA interstrand cross-links, was more effective in killing human cancer cell lines (H460, H1299, and PC3 than combining ATO and melphalan or thiotepa. We further demonstrated that the combination treatment of H460 cells with BO-1012 and ATO resulted in severe G2/M arrest and apoptosis. In a xenograft mouse model, the combination treatment with BO-1012 and ATO synergistically reduced tumor volumes in nude mice inoculated with H460 cells. Similarly, the combination of BO-1012 and ATO effectively reduced the growth of cisplatin-resistant NTUB1/P human bladder carcinoma cells. Furthermore, the repair of BO-1012-induced DNA interstrand cross-links was significantly inhibited by ATO, and consequently, γH2AX was remarkably increased and formed nuclear foci in H460 cells treated with this drug combination. In addition, Rad51 was activated by translocating and forming foci in nuclei on treatment with BO-1012, whereas its activation was significantly suppressed by ATO. We further revealed that ATO might mediate through the suppression of AKT activity to inactivate Rad51. Taken together, the present study reveals that a combination of bifunctional alkylating agents and ATO may be a rational strategy for treating cancers with inherited or acquired drug resistance.

  16. Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs

    International Nuclear Information System (INIS)

    Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.

    2010-01-01

    lower levels is considered to be less likely to result in toxicity following 28 days of exposure. Sex-related differences were seen in rats. Male rats appeared to have greater sensitivity to nephrotoxicity, while female animals had a greater incidence of hepatoxicity and changes in hematological parameters evaluated, especially at a dose of 500 mg/kg/day, which correlated to the higher plasma drug levels in female rats. It appeared that dogs were generally more sensitive than rats to oral administration of PMCol. Further examination of the potential toxic effects of PMCol in longer term studies is required prior to understanding the full risks of PMCol administration as a chemopreventative agent.

  17. Voglibose in Combination of Three Hypoglycemic Agents in the Treatment of Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    V.I. Pankivn

    2016-09-01

    Full Text Available The aim of the study — clinical and metabolic rationale for the selection of the third hypoglycemic agent to enhance the effectiveness of treatment in patients with diabetes mellitus (DM type 2, assessment of the impact of the therapy intensification due to the addition of voglibose on carbohydrate metabolism parameters, which have not reached target levels during the combination therapy with metformin and glimepiride. Materials and methods. We observed 45 patients with DM type 2, who have not reached the targets of carbohydrate metabolism under the influence of previous treatments (metformin and glimepiride. After the initial clinical examination, patients were divided into two groups. In the first group (n = 30, wе added to the treatment the drug voglibose (Voxid, production of Kusum Pharm Ltd, Ukraine 0.2 mg before breakfast, lunch and dinner for 12 weeks. Results. After 12 weeks of treatment, the level of glycated hemoglobin (НbА1с in the first group decreased by 1.5 [1.1; 1.9] % (p  0.05. 80 % of patients achieved target levels of glycemia. The first group of patients showed a significant increase in HOMA-β index by 24.9 %, as well as a reduction of insulin resistance (HOMA-IR by 31.5 %. After 12 weeks of therapy, there was a statistically significant decrease in body weight by 2.1 kg in the first group of patients and no response in patients of the second group. Safety has been proveв in terms of the functional state of the liver and kidneys in this therapy. Conclusions. Adding voglibose for intensification of therapy in patients with type 2 DM, who had previously received metformin and glimepiride, has led to a significant improvement in carbohydrate metabolism (decrease in HbA1c by 1.5 %. Better control of carbohydrate metabolism during the combination therapy with metformin, glimepiride, and voglibose is accompanied by an increase of functional activity of pancreatic β-cells, a decrease in insulin resistance in the

  18. A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin.

    Science.gov (United States)

    Shukla, Mahendra; Jaiswal, Swati; Sharma, Abhisheak; Srivastava, Pradeep Kumar; Arya, Abhishek; Dwivedi, Anil Kumar; Lal, Jawahar

    2017-05-01

    Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability. In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin. As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague-Dawley rats, the optimized SNEDDS of curcumin-phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS. The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.

  19. EDGE study in Russian Federation: efficacy and safety of vildagliptine in comparison with other oral antidiabetic agents in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Gagik Radikovich Galstyan

    2013-06-01

    Full Text Available According to international consensus, metformin is acknowledged as a first-line therapeutic agent for type 2 diabetes mellitus (T2DM. However, in most cases this treatment eventually requires intensification by supplementation with other hypoglycemic medications. The aim of the EDGE study (Effective Diabetes control with vildaGliptin and vildagliptin/mEtformin was to assess the efficacy and safety of vildagliptin in comparison with other oral agents in routine management of patients with T2DM that has been poorly controlled by metformin monotherapy.

  20. Use of simulated patients to evaluate combined oral contraceptive dispensing practices of community pharmacists.

    Directory of Open Access Journals (Sweden)

    Paulo Roque Obreli-Neto

    Full Text Available BACKGROUND: Combined oral contraceptive (COC use is the most commonly used reversible method of birth control. The incorrect use of COCs is frequent and one of the most common causes of unintended pregnancies. Community pharmacists (CPs are in a strategic position to improve COC use because they are the last health professional to interact with patients before drug use. OBJECTIVE: To evaluate the COC dispensing practices of CPs in a developing country. METHOD: A cross-sectional study was conducted in community pharmacies of Assis and Ourinhos microregions, Brazil, between June 1, 2012, and October 30, 2012. Four simulated patients (SPs (with counseled audio recording visited community pharmacies with a prescription for Ciclo 21(® (a COC containing ethinyl estradiol 30 mcg + levonorgestrel 15 mcg. The audio recording of every SP visit was listened to independently by 3 researchers to evaluate the COC dispensing practice. The percentage of CPs who performed a screening for safe use of COCs (i.e., taking of patients' medical and family history, and measuring of blood pressure and provided counseling, as well as the quality of the screening and counseling, were evaluated. RESULTS: Of the 185 CPs contacted, 41 (22.2% agreed to participate in the study and finished the study protocol. Only 3 CPs asked the SP a question (1 question asked by each professional, and all of the questions were closed-ended, viz., "do you smoke?" (n = 2 and "what is your age?" (n = 1. None of the CPs measured the patient's blood pressure. Six CPs provided counseling when dispensing COCs (drug dosing, 5 CPs; possible adverse effects, 2 CPs, and one CP provided counseling regarding both aspects. CONCLUSION: The CPs evaluated did not dispense COC appropriately and could influence in the occurrence of negatives therapeutic outcomes such as adverse effects and treatment failure.

  1. Magnetic resonance cholangiopancreatography (MRCP) using new negative per-oral contrast agent based on superparamagnetic iron oxide nanoparticles for extrahepatic biliary duct visualization in liver cirrhosis.

    Science.gov (United States)

    Polakova, Katerina; Mocikova, Ingrid; Purova, Dana; Tucek, Pavel; Novak, Pavel; Novotna, Katerina; Izak, Niko; Bielik, Radoslav; Zboril, Radek; Miroslav, Herman

    2016-12-01

    Magnetic resonance cholangiopancreatography (MRCP) is often used for imaging of the biliary tree and is required by surgeons before liver transplantation. Advanced liver cirrhosis and ascites in patients however present diagnostic problems for MRCP. The aim of this study was to find out if the use of our negative per-oral contrast agent containing superparamagnetic iron oxide nanoparticles (SPIO) in MRCP is helpful for imaging of hepatobiliary tree in patients with liver cirrhosis. Forty patients with liver cirrhosis were examined on a 1.5 T MR unit using standard MRCP protocol. Twenty patients (group A) underwent MRCP after administration of per-oral SPIO contrast agent 30 min before examination. In group B, twenty patients were examined without per-oral bowel preparation. Ascites was present in eleven patients from group A and in thirteen patients in group B. Four radiologists analyzed MR images for visibility and delineation of the biliary tree. χ 2 tests were used for comparison of the visibility of intrahepatic and extrahepatic biliary ducts in patients with and without ascites. Better extrahepatic biliary duct visualization and visibility of extraluminal pathologies in patients with ascites was proved after administration of SPIO contrast agent. No statistically significant difference between group A and B was found for visualization of extrahepatic biliary ducts in patients without ascites. Delineation of intrahepatic biliary ducts was independent on bowel preparation. Application of our negative per-oral SPIO contrast agent before MRCP improves the visualization of extrahepatic biliary ducts in patients with ascites which is helpful during the liver surgery, mainly in liver transplantation.

  2. Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents.

    Science.gov (United States)

    Noronha, Vanita; Joshi, Amit; Patil, Vijay Maruti; Banavali, Shripad D; Gupta, Sudeep; Parikh, Purvish M; Marfatia, Shalaka; Punatar, Sachin; More, Sucheta; Goud, Supriya; Nakti, Dipti; Prabhash, Kumar

    2018-04-01

    We aimed to find the optimal route of iron supplementation in patients with malignancy and iron deficiency (true or functional) anemia not receiving erythropoiesis stimulating agents (ESA). Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) 10% were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, quality of life (QoL), toxicity, response and overall survival. A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm. Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and -0.16 g/dL (SD: 1.36) in oral arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients (14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade) developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron and none on oral iron had hypersensitivity, P = 0.06. QoL was not significantly different between the two arms. IV iron was not superior to oral iron in patients with malignancy on chemotherapy and iron deficiency anemia. © 2017 John Wiley & Sons Australia, Ltd.

  3. Combining human and machine intelligence to derive agents' behavioral rules for groundwater irrigation

    Science.gov (United States)

    Hu, Yao; Quinn, Christopher J.; Cai, Ximing; Garfinkle, Noah W.

    2017-11-01

    For agent-based modeling, the major challenges in deriving agents' behavioral rules arise from agents' bounded rationality and data scarcity. This study proposes a "gray box" approach to address the challenge by incorporating expert domain knowledge (i.e., human intelligence) with machine learning techniques (i.e., machine intelligence). Specifically, we propose using directed information graph (DIG), boosted regression trees (BRT), and domain knowledge to infer causal factors and identify behavioral rules from data. A case study is conducted to investigate farmers' pumping behavior in the Midwest, U.S.A. Results show that four factors identified by the DIG algorithm- corn price, underlying groundwater level, monthly mean temperature and precipitation- have main causal influences on agents' decisions on monthly groundwater irrigation depth. The agent-based model is then developed based on the behavioral rules represented by three DIGs and modeled by BRTs, and coupled with a physically-based groundwater model to investigate the impacts of agents' pumping behavior on the underlying groundwater system in the context of coupled human and environmental systems.

  4. Effect of Combination Therapy with Neuroprotective and Vasoprotective Agents on Cerebral Ischemia.

    Science.gov (United States)

    Yang, Jiping; Yang, Bei; Xiu, Baoxin; Qi, Jinchong; Liu, Huaijun

    2018-05-01

    Because most tested drugs are active against only one of the damaging processes associated with stroke, other mechanisms may cause cellular death. Thus, a combination of protective agents targeting different pathophysiological mechanisms may obtain better effects than a single agent. The major objective of this study was to investigate the effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) after controlled ischemic brain injury in rabbits. Animals were randomly assigned to one of the following groups: sham group, saline-treated control group or NGF+VEGF-treated group. Animals received an intracerebral microinjection of VEGF and NGF or saline at 5 or 8 hours after ischemia. The two specified time points of administration were greater than or equal to the existing therapeutic time window for monoterapy with VEGF or NGF alone (3 or 5 hours of ischemia). Infarct volume, water content, neurological deficits, neural cell apoptosis and the expression of caspase-3 and Bcl-2 were measured. Compared with saline-treated controls, the combination therapy of VEGF and NGF significantly reduced infarct volume, water content, neural cell apoptosis and the expression of caspase-3, up-regulated the expression of Bcl-2 and improved functional recovery (both ple « facteur de croissance des nerfs » (ou « NGF » en anglais). Méthodes: Les animaux ont été attribués au hasard à l'un des groupes suivants : ceux ayant reçu un traitement fictif ; ceux, du groupe témoin, ayant bénéficié d'un traitement à base de solution saline ; et finalement ceux ayant été traités au moyen des VEGF et NGF. À noter que les lapins ont reçu une micro-injection intracérébrale de VEGF et de NGF ou de solution saline 5 heures ou 8 heures à la suite de leur AVC. Ces deux délais d'administration des VEGF et NGF sont équivalents ou supérieurs aux délais actuels d'administration des VEGF ou NGF à titre de monothérapie (3 heures ou 5

  5. Enhancement of radioresponse by combined treatment with flavopiridol, a cycline dependent kinase (CDK) inhibitor, in oral cancer cells

    International Nuclear Information System (INIS)

    Mihara, Mariko; Mano, Takamitsu; Ueyama, Yoshiya; Shintani, Satoru; Li, Syunnann; Klosek, S.; Hamakawa, Hiroyuki

    2005-01-01

    Cyclin dependent kinases (CDKs) play a pivotal role in cell cycle regulation. Flavopiridol is known to potently inhibit such CDKs as CDK1, CDK2, CDK4, CDK7. We already reported that flavopiridol inhibited the growth of oral squamous cell carcinoma (OSCC) cells and induced apoptosis in OSCC cells. In the present study, we investigated whether the treatment with flavopiridol improves the response to radiosensitivity in OSCC cell lines. In an in vitro study, there was a cooperative antiproliferative effect of combined treatment with flavopiridol and radiation in OSCC cell lines. Tumor xenograft studies demonstrated that the combination of flavopiridol and radiation caused growth inhibition and tumor regression of well-established OSCC tumor in athymic mice. Overall, we concluded that flavopiridol enhances tumor radioresponse and it is considered a suitable candidate drug in the treatment of oral cancer. (author)

  6. Assessement of the effect of Pyrimetin in combined injury with external irradiation and oral cerium-144 incorporation

    International Nuclear Information System (INIS)

    Kiradzhiev, G.; Khadzhidekova, E.

    1985-01-01

    The effect of the preparation Pyrimetin on rats, subjected to external irradiation combined with oral cerium 144 incorporation was studied. LD 50/30 of cerium-144 was used as biological criterion. It was shown that by this criterion Pyrimetin essentially abolished the potentiated by external radiation effect of cerium. Probably, the preparation leads to normalization of the gastro-intestinal motor function and the dose loading of the colon

  7. [Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study].

    Science.gov (United States)

    Zhang, Xi-ping; Zhang, Xiang; Yang, Hong-jian; Zou, De-hong; He, Xiang-ming; Yu, Xing-fei; Li, Yong-feng

    2015-07-01

    To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P drug B and L (P chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.

  8. Topical coal tar alone and in combination with oral methotrexate in management of psoriasis : a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Prasad PVS

    1997-01-01

    Full Text Available Thirty five patients admitted with psoriasis were analysed. 16 patients received 20% crude coal tar and 19 patients received 20% crude coal tar along with methotrexate in a weekly oral schedule (15mg/wk. After 4 weeks of therapy there was total clearence in 52.6% of the patients with combination therapy, whereas only 12.5% of the patients with conventional therapy achieved this.

  9. Combination of FVIII and by-passing agent potentiates in vitro thrombin production in haemophilia A inhibitor plasma.

    Science.gov (United States)

    Klintman, Jenny; Astermark, Jan; Berntorp, Erik

    2010-11-01

    The by-passing agents, recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC), are important tools in the treatment of patients with haemophilia A and high-responding inhibitory antibodies. It has been observed clinically that in some patients undergoing immune tolerance induction the bleeding frequency decreases, hypothetically caused by a transient haemostatic effect of infused FVIII not measurable ex vivo. We evaluated how by-passing agents and factor VIII (FVIII) affect thrombin generation (TG) in vitro using plasma from 11 patients with severe haemophilia A and high titre inhibitors. Samples were spiked with combinations of APCC, rFVIIa and five different FVIII products. Combination of APCC and FVIII showed a synergistic effect in eliciting TG (Pproducts. When rFVIIa and FVIII were combined the interaction between the preparations was found to be additive. APCC and rFVIIa were then combined without FVIII, resulting in an additive effect on thrombin production. Each product separately increased TG above baseline. In conclusion, the amount of thrombin formed in vitro by adding a by-passing agent, was higher in the presence of FVIII. Our findings support the use of FVIII in by-passing therapy to optimize the haemostatic effect. © 2010 Blackwell Publishing Ltd.

  10. In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    Songzhe eHE

    2015-05-01

    Full Text Available Objective To investigate the in vitro and in vivo antibacterial activities of tigecycline and other 13 common antimicrobial agents, alone or in combination, against multi-drug resistant Acinetobacter baumannii.MethodsAn in vitro susceptibility test of 101 Acinetobacter baumannii was used to detect minimal inhibitory concentrations (MICs. A mouse lung infection model of multi-drug resistant Acinetobacter baumannii,established by the ultrasonic atomization method, was used to define in vivo antimicrobial activities.Results Multi-drug resistant Acinetobacter baumannii showed high sensitivity to tigecycline (98% inhibition, polymyxin B (78.2% inhibition, and minocycline (74.2% inhibition. However, the use of these antimicrobial agents in combination with other antimicrobial agents produced synergistic or additive effects. In vivo data showed that white blood cell (WBC counts in drug combination groups C (minocycline + amikacin and D (minocycline + rifampicin were significantly higher than in groups A (tigecycline and B (polymyxin B (P < 0.05, after administration of the drugs 24h post-infection. Lung tissue inflammation gradually increased in the model group during the first 24h after ultrasonic atomization infection; vasodilation, congestion with hemorrhage were observed 48h post infection. After three days of anti-infective therapy in groups A, B, C and D, lung tissue inflammation in each group gradually recovered with clear structures. The mortality rates in drug combination groups (groups C and D were much lower than in groups A and B.ConclusionThe combination of minocycline with either rifampicin or amikacin is more effective against multidrug-resistant Acinetobacter baumannii than single-agent tigecycline or polymyxin B. In addition, the mouse lung infection by ultrasonic atomization is a suitable model for drug screening and analysis of infection mechanism.

  11. Combination of Multi-Agent Systems and Wireless Sensor Networks for the Monitoring of Cattle.

    Science.gov (United States)

    Barriuso, Alberto L; Villarrubia González, Gabriel; De Paz, Juan F; Lozano, Álvaro; Bajo, Javier

    2018-01-02

    Precision breeding techniques have been widely used to optimize expenses and increase livestock yields. Notwithstanding, the joint use of heterogeneous sensors and artificial intelligence techniques for the simultaneous analysis or detection of different problems that cattle may present has not been addressed. This study arises from the necessity to obtain a technological tool that faces this state of the art limitation. As novelty, this work presents a multi-agent architecture based on virtual organizations which allows to deploy a new embedded agent model in computationally limited autonomous sensors, making use of the Platform for Automatic coNstruction of orGanizations of intElligent Agents (PANGEA). To validate the proposed platform, different studies have been performed, where parameters specific to each animal are studied, such as physical activity, temperature, estrus cycle state and the moment in which the animal goes into labor. In addition, a set of applications that allow farmers to remotely monitor the livestock have been developed.

  12. Apoptotic efficiency of aqueous extracts of turmeric, garlic and their active compounds in combination with Tamoxifen in lung and oral cancers: A comparative study

    Directory of Open Access Journals (Sweden)

    Satish Kumar Vemuri

    2018-06-01

    Full Text Available Anticancer treatment against oral and lung cancers has caught the eye of oncologist and researchers worldwide as most common cause deaths in India and worldwide is due to these cancers and most of the treatment strategies employed are not showing any effectiveness against neoplastic ability of the cancers. One of the reasons for cancer deaths could be because of poor prognosis and associated therapies. The existing cancer agents are being re-evaluated and development of new mechanisms of treatment being explored continuously, but it’s inadequate in offering treatment. Therefore, endeavors for new anticancer agents with high efficacy and considerable side effects still going on. The literature reviews shows numerous medicinal plants exhibiting anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic properties and these effects were reported by conducting both in vitro experiments and animal studies. Use of natural phytochemical compounds in cancer chemoprevention is an emerging strategy to forestall the cancer progression or cure cancer.In the present study we have attempted to evaluate the efficacy of Curcumin longa and Allium sativum aqueous extracts individually and in combination with its active compounds (Curcumin and Quercetin and also with Tamoxifen hydrochloride. Our results suggest that aqueous extracts of Curcumin longa and Allium sativum were effective in inducing apoptosis and cell death in two immortal cell lines i.e. A549 and SCC-9 (Adeno carcinoma of lung, squamous cell carcinoma of tongue, but there was no apoptosis or cell senescence in normal cell line (HEK 293. There was significant increase in apoptosis and cell senescence in combination therapy. Hence a combination of natural extracts along with Tamoxifen can be considered an alternate in cancer treatments but this requires more research. Keywords: Curcumin longa, Allium sativum, Tamoxifen hydrochloride, A549, SCC-9, HEK 293 cell lines

  13. Skin patch and vaginal ring versus combined oral contraceptives for contraception.

    Science.gov (United States)

    Lopez, Laureen M; Grimes, David A; Gallo, Maria F; Stockton, Laurie L; Schulz, Kenneth F

    2013-04-30

    The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance. To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs). Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials. We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC. Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We also assessed the quality of evidence for this review. We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less

  14. Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

    Science.gov (United States)

    Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas

    2013-10-01

    The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  15. The pharmacokinetics and safety profile of oral ganciclovir in combination with trimethoprim in HIV- and CMV-seropositive patients

    Science.gov (United States)

    Jung, Donald; AbdelHameed, Magdy H; Hunter, John; Teitelbaum, Philip; Dorr, Albert; Griffy, Kay

    1999-01-01

    Aims We investigated the pharmacokinetics and safety profile of oral ganciclovir coadministered with trimethoprim in HIV-and CMV-seropositive patients. Methods In an open-label, randomized, 3-way crossover study, 12 adult males received oral ganciclovir 1000 mg every 8h, oral trimethoprim 200 mg once daily, or both drugs concomitantly in a sequence of three 7-day treatment periods. Pharmacokinetic parameters were determined and adverse events recorded for each treatment. Results The presence of trimethoprim significantly decreased CLr (12.9%, P = 0.0068) and increased t1/2 (18.1%, P = 0.0378) of ganciclovir. However, these changes are unlikely to be clinically meaningful. There were no statistically significant changes in trimethoprim pharmacokinetic parameters in the presence of ganciclovir, with the exception of a 12.7% increase in Cmin. Ganciclovir was well tolerated when administered alone or in combination with trimethoprim. Conclusions There was no clinically significant pharmacokinetic interaction between oral ganciclovir and trimethoprim when coadministered. PMID:10215748

  16. Effect of food and acid-reducing agents on the absorption of oral targeted therapies in solid tumors

    NARCIS (Netherlands)

    Willemsen, A.E.C.A.B.; Lubberman, F.J.E.; Tol, J.; Gerritsen, W.R.; Herpen, C.M.L. van; Erp, N. van

    2016-01-01

    Oral targeted therapies represent an increasingly important group of drugs within modern oncology. With the shift from intravenously to orally administered drugs, drug absorption is a newly introduced factor in drug disposition. The process of absorption can have a large effect on inter- and

  17. Evaluation of the efficacy of separate oral supplements compared with the combined oral supplements of vitamins C and E on sperm motility in Wistar rats.

    Science.gov (United States)

    Ogli, S A; Enyikwola, O; Odeh, S O

    2009-12-01

    Infertility is a major reproductive and social problem with a worldwide prevalence of 10-15%. While 11.8-39.0% of infertility cases are attributable to the female, 15.8-42.4% is attributed to the male and 8.0-11.1% to unknown factors. The study investigated the efficacy of the single versus combined regimes of antioxidant vitamins C and E oral supplements on sperm motility in the reproductively matured Wistar rats. Twenty [20] male Wistar rats aged 12 weeks and weighing between 182 g and 252 g were randomly grouped into 4 experimental blocks [A-D] of 5 rats each. Block A rats were served combined daily dose of 90 mg vitamin C and 15 mg vitamin E, block B rats had no treatment and served as control, block C rats were served daily dose of 15 mg vitamin E only while block D rats were served daily dose of 90 mg vitamin C only; all treatments were administered for 28 days. On the 29th day, the rats were humanely sacrificed and semen analyzed for sperm motility. The study showed that treatment with vitamins C and E as single regime significantly improved [Ppercentage sperm motility by 70 and 75 folds respectively while significantly decreasing [P<0.01] the non-progressive [category c] mean percent sperm motility by 8 and 5 folds respectively compared to the control mean percent sperm motility. We therefore conclude that sperm motility in the Wistar rats is significantly improved with the separate oral supplements of vitamins C and E as compared with the combined supplements.

  18. A hybrid approach to decision making and information fusion: Combining humans and artificial agents

    NARCIS (Netherlands)

    Groen, Frans C.A.; Pavlin, Gregor; Winterboer, Andi; Evers, Vanessa

    This paper argues that hybrid human–agent systems can support powerful solutions to relevant problems such as Environmental Crisis management. However, it shows that such solutions require comprehensive approaches covering different aspects of data processing, model construction and the usage. In

  19. Comparison of combined hormonal vaginal ring with ultralow-dose combined oral contraceptive pills in the management of heavy menstrual bleeding: A pilot study.

    Science.gov (United States)

    Agarwal, N; Gupta, M; Kriplani, A; Bhatla, N; Singh, N

    2016-01-01

    The aim of this study was to compare combined hormonal vaginal ring with ultralow-dose combined oral contraceptive (COC) pills in management of heavy menstrual bleeding (HMB). Fifty patients were randomised into Group I: vaginal ring (n = 25) and group II: COC pills (n = 25). Menstrual blood loss (MBL) was assessed at baseline, 1, 3 and 6 months (while on treatment) and at 9 months (3 months after stopping therapy). There was significant reduction in baseline pictorial blood loss assessment chart (PBAC) score from 440 ± 188 (Mean ± SD) to 178 ± 95, 139 ± 117, 112 ± 84 and 120 ± 108 in group I and from 452 ± 206 to 204 ± 152, 179 ± 125, 176 ± 164 and 202 ± 167 in group II at 1, 3, 6 and 9 months, respectively (p = 0.001). Reduction in MBL was 72% and 62% at 6 months and up to 71% and 55% at 9 months in group I and group II, respectively (p = 0.001). Reduction in MBL with ring was greater at higher baseline PBAC score but lesser in patients with fibroid > 2 cm. Combined vaginal hormonal treatment for HMB is as effective as oral hormonal therapy, with minor and transient side effects and persistence of response after cessation of therapy.

  20. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2012-07-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

  1. Cost-effectiveness of combined oral bisphosphonate therapy and falls prevention exercise for fracture prevention in the USA.

    Science.gov (United States)

    Mori, T; Crandall, C J; Ganz, D A

    2017-02-01

    We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone. The purpose of this study was to examine the cost-effectiveness of the combined strategy of oral bisphosphonate therapy for 5 years and falls prevention exercise for 1 year compared with either strategy in isolation. We calculated incremental cost-effectiveness ratios [ICERs] (2014 US dollars per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women with different starting ages (65, 70, 75, and 80) without prior history of hip, vertebral, or wrist fractures over a lifetime horizon from the societal perspective. At ages 65, 70, 75, and 80, the combined strategy had ICERs of $202,020, $118,460, $46,870, and $17,640 per QALY, respectively, compared with oral bisphosphonate therapy alone. The combined strategy provided better health at lower cost than falls prevention exercise alone at ages 70, 75, and 80. In deterministic sensitivity analyses, results were particularly sensitive to the change in the opportunity cost of participants' time spent exercising. In probabilistic sensitivity analyses, the probabilities of the combined strategy being cost-effective compared with the next best alternative increased with age, ranging from 35 % at age 65 to 48 % at age 80 at a willingness-to-pay of $100,000 per QALY. Among community-dwelling US white women ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a willingness-to-pay of $100,000 per QALY, compared with oral bisphosphonate therapy only. This analysis will help clinicians and policymakers make better decisions about treatment

  2. Patients' oral hydration levels and incidence of immediate to short-term mild side-effects in contrast agent enhanced MRI diagnostics

    International Nuclear Information System (INIS)

    Jonker, Leon; Fallahi, Farshid

    2015-01-01

    Aim: Gadolinium-based contrast agents for radiodiagnostic purposes can lead to side effects, including nephrotoxicity in patients with renal insufficiency. This study evaluated whether the occurrence of mild side effects from gadolinium-based contrast enhanced magnetic resonance imaging (MRI) correlates to patients' oral hydration levels. Methods: Oral fluid intake levels 24 h pre- and 24 h post-MRI, as well as incidence of mild side-effects experienced 30 min and 24 h post-MRI were recorded by using a patient self-reporting questionnaire. Results: A total of 174 patients, 29 controls, 98 administered Prohance and 47 receiving Dotarem, were enrolled. Overall, the most frequently reported side-effect was headache; nausea only occurred in patients receiving contrast agent. One or more side-effects experienced 24 h following the MRI scan were reported by 10% (controls), 24% (Prohance) and 22% (Dotarem) of patients, respectively. Multivariate ordinal regression analysis showed that only male gender (OR 0.24, 95% CI 0.11–0.53) was statistically significantly associated with a decreased incidence of side-effects 30 min after MRI. At 24-h post MRI, a lack of contrast agent (OR 0.40, 95% CI 0.09–1.74) and male gender (OR 0.46, 95% CI 0.19–1.09) were associated with fewer side-effects. Conclusions: The level oral fluid intake before and after undergoing gadolinium-based contrast-enhanced MRI does not appear to markedly affect the incidence of common undesirable mild symptoms experienced shortly after the procedure. Confounding differences between patients in reporting side-effects may contribute to these findings. - Highlights: • We assess the incidence of patient-reported side-effects after contrast-enhanced MRI. • We examine the potential impact of oral hydration levels on side-effects. • Patient reported side-effects are high compared to those reported by clinicians. • Female gender and contrast agent itself are associated with increased side

  3. Effectiveness and tolerability of second-line therapy with vildagliptin versus other oral agents in type 2 diabetes (EDGE): post-hoc subanalysis of the Belgian data.

    Science.gov (United States)

    Hoste, J; Daci, E; Mathieu, C

    2014-06-01

    To assess the efficacy and safety of vildagliptin versus other oral glucose-lowering drugs added to antidiabetic monotherapy in Belgian patients with type 2 diabetes mellitus, in comparison to the global EDGE study results. This is a pre-specified post-hoc subanalysis of the Belgian patient cohort from a worldwide 1-year observational study that compared the effectiveness and tolerability of vildagliptin to other oral antidiabetic agents in type 2 diabetes patients failing monotherapy with oral glucose-lowering agents (EDGE). A total of 1793 Belgian patients were enrolled. Physicians could add any oral antidiabetic drug and patients entered either into the vildagliptin or the comparator cohort. The primary effectiveness and tolerability endpoint was defined as the proportion of patients having a treatment response (HbA1c reduction from baseline to month 12 endpoint >0·3%) without hypoglycemia, weight gain, peripheral oedema, or gastrointestinal side-effects. In the Belgian population, 37·8% of patients in the vildagliptin group and 32·8% in the comparator group had a decrease in HbA1c of >0·3% without the predefined tolerability issues of hypoglycemia, weight gain, oedema or, gastrointestinal complaints (primary endpoint), resulting in an unadjusted odds ratio of 1·24 (95% CI: 0·96-1·61). Mean HbA1c change from baseline was -0·81% in the vildagliptin cohort and -0·75% in the comparator cohort. Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (14·9% versus 14·5% in the compactor group) and serious adverse events (2·7% versus 2·5% in the comparator group). In this EDGE subgroup of Belgian patients with type 2 diabetes who do not achieve the glycemic targets with monotherapy, a similar trend as in the global EDGE study was observed. Adding vildagliptin as a second oral glucose-lowering agent resulted in lowering HbA1c to <7% without weight gain, hypoglycemia or peripheral oedema in a higher proportion of

  4. Suspected adverse reactions to oral administration of a praziquantel-pyrantel combination in captive cheetahs (Acinonyx jubatus).

    Science.gov (United States)

    Whitehouse-Tedd, Katherine M; Smith, Liesl; Budd, Jane A; Lloyd, Christopher G

    2017-11-15

    OBJECTIVE To characterize adverse reactions to oral administration of a combination of praziquantel and pyrantel embonate or pyrantel pamoate, with or without oxantel embonate, in captive cheetahs (Acinonyx jubatus). DESIGN Retrospective case series and case-control study. ANIMALS 16 captive cheetahs with signs of adverse reaction to oral administration of praziquantel and pyrantel, with or without oxantel embonate (affected group), and 27 cheetahs without such reactions (unaffected group), all from 3 independent facilities. PROCEDURES Medical records and postmortem findings for affected cheetahs were reviewed and compared with those of unaffected animals. Anthelmintic doses administered, age, and sex of cheetahs were compared between groups. RESULTS 3 reactions in affected cheetahs were fatal, whereas the remainder ranged from mild to severe. Postmortem examination failed to reveal any disease processes or conditions to explain the deaths. No differences in anthelmintic dose were identified between affected and unaffected cheetahs for all facilities combined, and no correlation existed between dose and reaction severity. No association with sex was detected, but affected cheetahs were significantly younger than unaffected cheetahs. This difference was not significant after controlling for facility. CONCLUSIONS AND CLINICAL RELEVANCE Cheetahs were concluded to have had an adverse reaction to the praziquantel-pyrantel combination because of temporal proximity of onset of clinical signs to dose administration, similarity of signs to those reported for toxicosis in other species for these drugs, and a lack of other disease process or environmental explanatory factors. A highly cautious approach to the use of this drug combination is recommended for cheetahs.

  5. [Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study].

    Science.gov (United States)

    Herzog, A; Buchholz, J; Ruess-Melzer, K; Lang, J; Kaser-Hotz, B

    2013-02-01

    Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

  6. Combination of Multi-Agent Systems and Wireless Sensor Networks for the Monitoring of Cattle

    Science.gov (United States)

    Barriuso, Alberto L.; De Paz, Juan F.; Lozano, Álvaro

    2018-01-01

    Precision breeding techniques have been widely used to optimize expenses and increase livestock yields. Notwithstanding, the joint use of heterogeneous sensors and artificial intelligence techniques for the simultaneous analysis or detection of different problems that cattle may present has not been addressed. This study arises from the necessity to obtain a technological tool that faces this state of the art limitation. As novelty, this work presents a multi-agent architecture based on virtual organizations which allows to deploy a new embedded agent model in computationally limited autonomous sensors, making use of the Platform for Automatic coNstruction of orGanizations of intElligent Agents (PANGEA). To validate the proposed platform, different studies have been performed, where parameters specific to each animal are studied, such as physical activity, temperature, estrus cycle state and the moment in which the animal goes into labor. In addition, a set of applications that allow farmers to remotely monitor the livestock have been developed. PMID:29301310

  7. From Mouth to Model: Combining in vivo and in vitro oral biofilm growth

    Directory of Open Access Journals (Sweden)

    Barbara Klug

    2016-09-01

    Full Text Available Oral biofilm studies based on simplified experimental setups are difficult to interpret. Models are limited mostly by the number of bacterial species observed and the insufficiency of artificial media. Few studies have attempted to overcome these limitations and to cultivate native oral biofilm. This study aimed to grow oral biofilm in vivo before transfer to a biofilm reactor for ex-situ incubation. The in-vitro survival of this oral biofilm and the changes in bacterial composition over time were observed. Six human enamel-dentin slabs embedded buccally in dental splints were used as biofilm carriers. Fitted individually to the upper jaw of 25 non-smoking male volunteers, the splints were worn continuously for 48 hours. During this time, tooth-brushing and alcohol-consumption were not permitted. The biofilm was then transferred on slabs into a biofilm reactor and incubated there for 48 hours while being nourished in BHI medium. Live/dead staining and confocal laser scanning microscopy were used to observe bacterial survival over four points in time: directly after removal (T0 and after 1h (T1, 24h (T2 and 48h (T3 of incubation. Bacterial diversity at T0 and T3 was compared with 454-pyrosequencing. Fluorescence in situ hybridization was performed to show specific taxa. Survival curves were calculated with a specially designed MATLAB script. Acacia and QIIME 1.9.1 were used to process pyrosequencing data. SPSS 21.0 and R 3.3.1 were used for statistical analysis.After initial fluctuations at T1, survival curves mostly showed approximation of the bacterial numbers to the initial level at T3. Pyrosequencing analysis resulted in 117 OTUs common to all samples. The genera Streptococcus and Veillonella (both Firmicutes dominated at T0 and T3. They make up two thirds of the biofilm. Genera with lower relative abundance had grown significantly at T3. FISH analysis confirmed the pyrosequencing results, i.e. the predominant staining of Firmicutes. We

  8. A comparison of detomidine in combination with saline, morphine or methadone in horses submitted to experimental oral stimuli

    Directory of Open Access Journals (Sweden)

    Rafael Costa Guilhen

    2015-12-01

    Full Text Available This study aimed to compare the sedative and cardiopulmonary effects of detomidine in combination with saline, morphine or methadone and to determine whether the addition of these opioids increases the degree of sedation in horses submitted to experimental oral stimuli. In a blinded, randomized, experimental study, six adult mares were evaluated using a crossover design with at least 15 days between trials: 10?g/kg detomidine in combination with saline (D/SAL, 0.1mg/kg morphine (D/ MORPH or 0.1mg/kg methadone (D/METH. The degree of sedation, response to oral stimuli and cardiopulmonary parameters were monitored for 120 minutes. Parametric data were analyzed using the ANOVA and Tukey’s tests, and non- parametric data were analyzed with the Kruskal-Wallis and Friedman’s tests with the post-Dunn test (P<0.05. The degree of sedation was significantly greater for the D/SAL than for the D/MORPH and D/METH treatments at 30 min. The horses´ responses to the oral stimuli decreased significantly following all treatments at 5 and 30 min from baseline values. The heart rate, respiratory rate, arterial pH and blood gas variables were all similar among the treatment groups. Mean arterial blood pressure was significantly higher in the D/MORPH group when compared with the D/SAL group between 75 and 120 min. It was concluded that all treatments provided sedative effects with mild cardiopulmonary changes. However the addition of morphine or methadone to detomidine did not improve the degree of sedation in horses submitted to experimental oral stimuli.

  9. Pharmacokinetics and brain distribution of tetrahydropalmatine and tetrahydroberberine after oral administration of DA-9701, a new botanical gastroprokinetic agent, in rats.

    Science.gov (United States)

    Jung, Ji Won; Kwon, Yong Sam; Jeong, Jin Seok; Son, Miwon; Kang, Hee Eun

    2015-01-01

    DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

  10. Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

    Science.gov (United States)

    Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David E; Thurber, Greg M

    2018-05-07

    Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

  11. Combinations of biocontrol agents for management of plant-parasitic nematodes and soilborne plant-pathogenic fungi.

    Science.gov (United States)

    Meyer, Susan L F; Roberts, Daniel P

    2002-03-01

    Numerous microbes are antagonistic to plant-parasitic nematodes and soilborne plant-pathogenic fungi, but few of these organisms are commercially available for management of these pathogens. Inconsistent performance of applied biocontrol agents has proven to be a primary obstacle to the development of successful commercial products. One of the strategies for overcoming inconsistent performance is to combine the disease-suppressive activity of two (or more) beneficial microbes in a biocontrol preparation. Such combinations have potential for more extensive colonization of the rhizosphere, more consistent expression of beneficial traits under a broad range of soil conditions, and antagonism to a larger number of plant pests or pathogens than strains applied individually. Conversely, microbes applied in combination also may have antagonistic interactions with each other. Increased, decreased, and unaltered suppression of the target pathogen or pest has been observed when biocontrol microbes have been applied in combination. Unfortunately, the ecological basis for increased or decreased suppression has not been determined in many cases and needs further consideration. The complexity of interactions involved in the application of multiple organisms for biological control has slowed progress toward development of successful formulations. However, this approach has potential for overcoming some of the efficacy problems that occur with application of individual biocontrol agents.

  12. Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

    Science.gov (United States)

    Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

    2011-01-01

    The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

  13. Combination oral and mechanical bowel preparations decreases complications in both right and left colectomy.

    Science.gov (United States)

    Midura, Emily F; Jung, Andrew D; Hanseman, Dennis J; Dhar, Vikrom; Shah, Shimul A; Rafferty, Janice F; Davis, Bradley R; Paquette, Ian M

    2018-03-01

    Before elective colectomy, many advocate mechanical bowel preparation with oral antibiotics, whereas enhanced recovery pathways avoid mechanical bowel preparations. The optimal preparation for right versus left colectomy is also unclear. We sought to determine which strategy for bowel preparation decreases surgical site infection (SSI) and anastomotic leak (AL). Elective colectomies from the National Surgical Quality Improvement Program colectomy database (2012-2015) were divided by (1) type of bowel preparation: no preparation (NP), mechanical preparation (MP), oral antibiotics (PO), or mechanical and oral antibiotics (PO/MP); and (2) type of colonic resection: right, left, or segmental colectomy. Univariate and multivariate analyses identified predictors of SSI and AL, and their risk-adjusted incidence was determined by logistic regression. When analyzed as the odds ratio compared with NP, the PO and PO/MP groups were associated with a decrease in SSI (PO = 0.70 [0.55-0.88] and PO/MP = 0.47 [0.42-0.53]; P < .01). Use of PO/MP was associated with a decrease in SSI across all types of resections (right colectomy = 0.40 [0.33-0.50], left colectomy = 0.57 [0.47-0.68], and segmental colectomy = 0.43 (0.34-0.54); P < .01). Similarly, use of PO/MP was associated with a decrease in AL in left colectomy = 0.50 ([0.37-0.69]; P < .01) and segmental colectomy = 0.53 ([0.36-0.80]; P < .01). Mechanical bowel preparation with oral antibiotics is the preferred preoperative preparation strategy in elective colectomy because of decreased incidence of SSI and AL. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The value of hysterosalpingography using non-ionic contrast agent combined with low-tensive drug in diagnosis of infertility

    International Nuclear Information System (INIS)

    Deng Qiwei; Liu Xiaojun; Shi Jianfen; Jiang Guohua; Ye Jinqing; Shen Jun; Song Ting

    2009-01-01

    Objective: To analyze the value of nonionic contrast agent combined with low tensive drug in the hysterosalpingography in diagnosis of infertility. Methods: 203 patients with infertility were randomly classified into two groups. Group 1 contained 108 patients administrated intramuscularly anisodamine (654-2) 30 minutes before hysterosalpingography. 95 patients in group 2 did not use 654-2. Non-ionic contrast agent was used in all patients. The image quality and post-contrast displaying status of uterus and uterine tube between the two groups were analyzed. Results: No allergic response occurred in all patients. The image quality and post-contrast displaying status of uterus and uterine tube of group 1 were obviously superior to that of group 2 (P<0.01). Conclusion: Hysterosalpingography clearly showed lesions of uterus and uterine tube when using non-ionic contrast agent combined with low-tensive drug. It is more safety with less side effects. The contraction of uterine tube can be relieved by the low-tensive drug effectively, so as to decrease the false positive rate, raise the diagnostic accuracy, and lessen patients sufferings. It is deserved to be applied generally. (authors)

  15. Osteo-odonto-keratoprosthesis surgery: a combined ocular-oral procedure for ocular blindness.

    Science.gov (United States)

    Tay, A B G; Tan, D T H; Lye, K W; Theng, J; Parthasarathy, A; Por, Y-M

    2007-09-01

    The aim of this retrospective study was to describe the oral procedures used in osteo-odonto-keratoprosthesis (OOKP) surgery, and the demographics and oral findings of candidate patients in Singapore. The OOKP procedure utilizes an autologous tooth-bone complex to mount a poly-methylmethacrylate optical cylinder, as an artificial cornea, stabilized by an overlying autologous buccal mucosal graft. Consecutive patients referred over 3 years for dental evaluation prior to OOKP surgery were included. A total of 21 patients underwent oral clinical and radiographic evaluation. The aetiology of blindness included Stevens-Johnson's syndrome (11 cases), chemical burns (9 cases) and multiple failed corneal grafts (1 case). Evaluation revealed that 12 patients were suitable for OOKP surgery, 8 were at risk of complication or failure and 1 had no usable teeth. Fourteen patients have undergone unilateral OOKP Stage 1 surgery successfully. Complications included fracture of a tooth from its lingual bone necessitating the harvesting of a second tooth (1 case), oronasal perforation (1 case), exposure of adjacent roots (5 teeth), lower lip paresthesia (2 cases) and submucosal scar band formation in the buccal mucosal graft donor site (10 cases). Thirteen patients have completed Stage 2 surgery, with attainment of their best possible visual potential following OOKP surgery.

  16. Vesiculo-erosive oral mucosal disease--management with topical corticosteroids: (1) Fundamental principles and specific agents available.

    Science.gov (United States)

    González-Moles, M A; Scully, C

    2005-04-01

    Vesiculo-erosive diseases of the oral mucosa pose a major challenge in oral medicine, because they are chronic, painful, and interfere with the daily activities and quality of life of the patients, including disturbing eating, drinking, talking, and personal relationships. Many are autoimmune diseases, and corticosteroid therapy is currently central to their treatment. These diseases present with inflammation and alterations to epithelial integrity, through cell and/or humoral immunity-mediated attack on epithelial-connective tissue targets. Until recently, despite their serious adverse effects, it was necessary to prescribe systemic corticosteroids to control severe erosive oral diseases. Now, however, many of these diseases can be controlled by high-potency topical corticosteroids, which have proved to be highly efficacious and to cause fewer adverse effects compared with systemic corticosteroids. Nevertheless, although topical corticosteroids are still the most widely used drugs in the practice of oral medicine, the scientific body of evidence for their use in the oral cavity is virtually non-existent, and therefore many of the protocols followed are, of necessity, drawn from experience of their use in a dermatological setting. This review aims to set out the key aspects of the use of topical corticosteroids in oral medicine. The issues covered include the indications and basic rules for their use, the types of corticosteroids, the drug selection, and the specific formulations.

  17. A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-β, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort.

    Science.gov (United States)

    Werner, Theresa L; Wade, Mark L; Agarwal, Neeraj; Boucher, Kenneth; Patel, Jesal; Luebke, Aaron; Sharma, Sunil

    2015-12-01

    JI-101 is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor β (PDGFR-β), and ephrin type-B receptor 4 (EphB4). None of the currently approved angiogenesis inhibitors have been reported to inhibit EphB4, and therefore, JI-101 has a novel mechanism of action. We conducted a pilot trial to assess the pharmacokinetics (PK), tolerability, and efficacy of JI-101 in combination with everolimus in advanced cancers, and pharmacodynamics (PD), tolerability, and efficacy of JI-101 in ovarian cancer. This was the first clinical study assessing anti-tumor activity of JI-101 in a combinatorial regimen. In the PK cohort, four patients received single agent 10 mg everolimus on day 1, 10 mg everolimus and 200 mg JI-101 combination on day 8, and single agent 200 mg JI-101 on day 15. In the PD cohort, eleven patients received single agent JI-101 at 200 mg twice daily for 28 day treatment cycles. JI-101 was well tolerated as a single agent and in combination with everolimus. No serious adverse events were observed. Common adverse events were hypertension, nausea, and abdominal pain. JI-101 increased exposure of everolimus by approximately 22%, suggestive of drug-drug interaction. The majority of patients had stable disease at their first set of restaging scans (two months), although no patients demonstrated a response to the drug per RECIST criteria. The novel mechanism of action of JI-101 is promising in ovarian cancer treatment and further prospective studies of this agent may be pursued in a less refractory patient population or in combination with cytotoxic chemotherapy.

  18. Color stabilization of porcine hemoglobin during spray-drying and powder storage by combining chelating and reducing agents.

    Science.gov (United States)

    Salvador, P; Toldrà, M; Parés, D; Carretero, C; Saguer, E

    2009-10-01

    This work focuses on the effects of adding a chelating agent - such as nicotinic acid (NA, 2% w/v) or nicotinamide (Nam, 2.5% w/v) - along with glucose as a reducing agent (G, 10% w/v) to fresh porcine hemoglobin in order to stabilize its red color during spray-drying and powder storage at room temperature. Correlations between the CIELAB color parameters and the relative percentages of the different hemoglobin derivatives (liganded and deliganded ferrohemoglobin, and methemoglobin) were analyzed. The results indicate that, although little effects could be observed for any of the combined treatments on fresh hemoglobin, they were effective against pigment autoxidation during dehydration and subsequent storage. From the results, it can also be concluded that glucose was the main contributor to the color stabilization of the hemoglobin powder, probably due to its high water retention capacity.

  19. Effect of Er, Cr: YSGG laser combined with oral basic treatment on inflammatory injury and apoptosis in patients with periodontitis

    Directory of Open Access Journals (Sweden)

    Wei-Xing Jin

    2017-09-01

    Full Text Available Objective: To study the effect of Er, Cr: YSGG laser combined with oral basic treatment on inflammatory injury and apoptosis in patients with periodontitis. Methods: Patients with chronic periodontitis who were treated in dental clinic of our hospital between February 2015 and March 2017 were selected as the research subjects and randomly divided into the group A who accepted ultrasonic dental cleaning, hand scaling combined with Er, Cr: YSGG laser treatment and the group B who received ultrasonic dental cleaning and hand scaling treatment. The contents of inflammatory response cytokines, protease molecules and apoptosis molecules in gingival crevicular fluid were detected before treatment and 1 week after treatment. Results: TNF-α, hs-CRP, IL-1β, IL-6, IL-8, EMMPRIN, CyPA, MMP2, MMP9, Smac, Bax, Fas and FasL contents in gingival crevicular fluid of both groups of patients 1 week after treatment were significantly lower than those before treatment, and TNF-α, hs-CRP, IL-1β, IL-6, IL-8, EMMPRIN, CyPA, MMP2, MMP9, Smac, Bax, Fas and FasL contents of group A 1 week after treatment were significantly lower than those of group B. Conclusion: Er, Cr: YSGG laser combined with oral basic treatment can inhibit the inflammatory injury and apoptosis in periodontal tissue of patients with periodontitis.

  20. The combined effect of laser and oral administration of Iranian propolis extract on skin wound healing in male rats

    Directory of Open Access Journals (Sweden)

    Nematollah Ghaibi

    2015-05-01

    Full Text Available Background: To date, a lot of research has been carried out on the effect of medications and surgical methods on the treatment of wounds, but no ideal achievement has been obtained yet. This study was conducted to investigate the single and combined effect of laser and propolis on skin wound healing in male rats. Methods: 40 Wistar male rats (200-250 g were divided into 4 groups (n= 10. All animals were anesthetized and sterile skin wound was created by surgical scissors. Control group had no treatment, the second group was treated with laser (10 mW, the third group was treated with oral propolis (100 mg /kg; 3 times /day and the forth group was treated with both laser and propolis. The wound healing level was measured based on the wound area and urinary hydroxyproline content. Results: Urinary hydroxyproline content was increased in groups treated with laser, propolis and combined laser and propolis compared to the control group (P<0.01, 0.05 and 0.01, respectively. Also at the end of the treatment period, the wound extent was significantly lower in the laser, propolis, and combined laser and propolis groups than the control (P<0.05, 0.05 and 0.01, respectively. There was no significant difference between treatment groups. Conclusion: Our results showed that oral administration of propolis or low power laser radiation can increase the wound healing rate.

  1. Comparative study of the efficacy of topical steroid and antibiotic combination therapy versus oral antibiotic alone when treating acute rhinosinusitis.

    Science.gov (United States)

    El-Hennawi, D M; Ahmed, M R; Farid, A M; Al Murtadah, A M

    2015-05-01

    Acute rhinosinusitis arises as a consequence of viral rhinitis, and bacterial infection can subsequently occur. Intranasal antibiotics as an adjunct to corticosteroids usually demonstrate the greatest symptom relief. We wanted to clinically evaluate the effects of a topical antibiotic and steroid combination administered intranasally, versus an oral antibiotic alone when treating acute rhinosinusitis. Forty patients with acute bacterial rhinosinusitis were divided into two groups. Group A received an antibiotic and steroid combination (ofloxacin 0.26 per cent and dexamethasone 0.053 per cent nasal drops) for 10 days, administered intranasally (5 drops in each nostril/8 hours). Group B, the control group, received an oral antibiotic alone (amoxicillin 90 mg/kg). Eight hours after commencing treatment, facial pain was more severe in group B and nasal obstruction was reduced in both groups. Ten days after commencing treatment, anterior nasal discharge was 0.15 per cent in group A and absent in group B. The application of a topical antibiotic and steroid combination into the nasal cavity is an effective way of treating uncomplicated, acute bacterial rhinosinusitis with the theoretical advantages of easy administration, high local drug concentration and minimal systemic adverse effects.

  2. In Vitro Bioactivity and Setting Times of White Portland Cement Combined with Different Radio Pacifying Agents

    Directory of Open Access Journals (Sweden)

    Coleman Nichola Jayne

    2017-01-01

    Full Text Available Commercial formulations based on 80:20 mixtures of Portland cement and bismuth oxide (a radiopacifying agent are used in dentistry as root-filling materials. This study compares the impact of two alternative radiopacifiers, barium sulphate and zirconium oxide, with that of bismuth oxide, on the setting times and bioactivity of white Portland cement. The findings indicate that bismuth oxide prolongs both the initial and final setting times of the cement, and that barium sulphate and zirconium oxide have no effect on this parameter. Hydroxyapatite (HA formed on the surfaces of all test samples within 7 days of exposure to simulated body fluid, indicating that they possess the potential to stimulate new hard tissue formation. Fourier transform infrared spectroscopy, the traditional technique for the identification of HA, was not appropriate for the analysis of these cement systems owing to the overlap of signals from each of the radiopacifiers with the characteristic P-O bending modes of HA in the 570 – 610 cm−1 region. In this respect, the P-O band at 965 cm−1 of HA in the Raman spectrum was found to be a suitable means of detection since it is discrete with respect to all signals arising from the radiopacifying agents and cement phases.

  3. SU-F-P-29: Impact of Oral Contrast Agent for Assisting in Outlining Small Intestine On Pelvic IMAT Dose in Patients with Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, R; Bai, W; Fan, X [The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei (China)

    2016-06-15

    Purpose: As the advanced intensity modulated arc therapy(IMAT) delivery systems becoming a main role of treatment ways, which places even greater demands on delivering accuracy. The impact of oral contrast agent (meglumine diatrizoate) for assisting in outlining the small intestine on pelvic IMAT dose in patients with cervical cancer was investigated. Methods: Ten cervical cancer patients for postoperative radiotherapy underwent CT scans, and the planning target volumes (PTV) and organs at risk (including the small intestine, rectum, bladder, colon and the left and right femoral head) were contoured. The IMAT plans were generated on Oncentra v4.1 planning system for each case, PTV was prescribed to 50.4 Gy in 28 fractions. Then another plan was generated by re-calculating the radiation dose after changing the electron density of the small bowel. The first plan (plan A) was the conventional IMAT plan (with oral contrast agent), and the second one (plan B) specified the electron density of the small bowel (without oral contrast agent). Paired t-test was used to compare the dose distribution between the two plans. Results: The PTV’s D2, D50, D95, V110, conformity index, and homogeneity index of plans A and B were 5610.5 vs. 5611.4 cGy (P=0.175), 5348.5 vs. 5348.0 cGy (P=0.869), 5039 vs. 5042.3 (P=0.518), 6.0% vs. 6.1 %( P=0.886), 0.1269 vs. 0.1271 (P=0.34) and 0.8421 vs. 0.8416 (P=0.598), respectively. The volumes of the small bowel receiving at least 30 Gy (V30) and the minimum dose of 2% volume accepted (D2) for plans A and B were 31.6% vs. 31.9% (P=0.371) and 5067.8 vs. 5085.4 cGy (P=0.377), while rectum V50 of the two plans was 12.4% vs. 12.1% (P=0.489). Conclusion: The oral contrast agent (meglumine diatrizoate) filling the small intestine does not lead to a significant increase in the pelvic IMAT dose in patients with cervical cancer.

  4. Peripheral arterial disease in a female using high-dose combined oral contraceptive pills.

    Science.gov (United States)

    Pallavee, P; Samal, Sunita; Samal, Rupal

    2013-01-01

    The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.

  5. Acute Diarrhoea in Children: Determination of Duration Using a Combined Bismuth Hydroxide Gel and Oral Rehydration Solution Therapy vs. Oral Rehydration Solution

    Directory of Open Access Journals (Sweden)

    Adriana Oviedo

    2016-12-01

    Full Text Available Oral rehydration salt (ORS treatment in young children with acute diarrhoea (AD has contributed to decrease mortality associated with dehydration although effective strategies to reduce morbidity associated with this disease are required. The aim of this study was to evaluate the diarrhoea duration when using combined colloidal bismuth hydroxide gel (CBHG and oral rehydration salt treatment compared with ORS therapy in children with AD. We designed a double-blind, randomised prospective study with treatment and control groups. Patients aged one to 12 years, with no prior pathology and with AD of less than 48 h were included. The Chi-squared and Mann-Whitney tests were used, as well as the Cox proportional hazards model and the Kaplan-Meier estimator. Patients were randomised into an ORS and CBHG treatment group and a control group for ORS plus placebo. (Average age: 3.2 years. The result of the post-treatment evaluation with respect to the average duration of AD was 25.5 h for the treated group vs. 41.5 h for the control group (p = 0.015. The average number of stools was 4.8 in the treated group and 8.2 in the control group (p = 0.032. We conclude that the use of CBHG plus ORS significantly reduced the duration of AD, the number of stools and the percentage of children with persistent AD after 24 h of treatment compared to the control group. AD remitted almost twice as fast in patients treated with CBHG and ORS compared to those who received ORS plus placebo.

  6. Immunological changes following a combined effect of chromic small dose γ-irradiation and toxic agents

    International Nuclear Information System (INIS)

    Shubik, V.M.; Zykova, I.A.

    1981-01-01

    Immunologic changes under conditions of durable effect of low dose γ-radiation on people in the case of combining radiation with the effect of low concentrations of toxic substances, are studied. Under the above effect, the appearance of deviations from the side of immunologic status is possible. Taking into account the important role of the immunity system in homeostasis preservation and the formation of a series of pathological states it is advisable to use figures, and characteristics inherent in the state of the cell immunity to autoallergic processes to estimate a combined effect of radiation and toxic substances on the organism of people [ru

  7. Combined Effects of Fe3O4 Nanoparticles and Chemotherapeutic Agents on Prostate Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Kanako Kojima

    2018-01-01

    Full Text Available Patients with metastatic castration-resistant prostate cancer (mCRPC have poor outcomes. Docetaxel (DTX-based therapy is a current standard treatment for patients with mCRPC. Approaches combining conventional chemotherapeutic agents and nanoparticles (NPs, particularly iron oxide NPs, may overcome the serious side effects and drug resistance, resulting in the establishment of new therapeutic strategies. We previously reported the combined effects of Fe3O4 nanoparticles (Fe3O4 NPs with DTX on prostate cancer cells in vitro. In this study, we investigated the combined effects of Fe3O4 NPs and rapamycin or carboplatin on prostate cancer cells in vitro. Treatment of DU145 and PC-3 cells with Fe3O4 NPs increased intracellular reactive oxygen species (ROS levels in a concentration-dependent manner. Treatment of both cell lines with 100 μg/mL Fe3O4 NPs for 72 h resulted in significant inhibition of cell viability with a different inhibitory effect. Combination treatments with 100 µg/mL Fe3O4 NPs and 10 µM carboplatin or 10 nM rapamycin in DU145 and PC-3 cells significantly decreased cell viability. Synergistic effects on apoptosis were observed in PC-3 cells treated with Fe3O4 NPs and rapamycin and in DU145 cells with Fe3O4 NPs and carboplatin. These results suggest the possibility of combination therapy with Fe3O4 NPs and various chemotherapeutic agents as a novel therapeutic strategy for patients with mCRPC.

  8. [Keratomycosis due to Fusarium oxysporum treated with the combination povidone iodine eye drops and oral fluconazole].

    Science.gov (United States)

    Diongue, K; Sow, A S; Nguer, M; Seck, M C; Ndiaye, M; Badiane, A S; Ndiaye, J M; Ndoye, N W; Diallo, M A; Diop, A; Ndiaye, Y D; Dieye, B; Déme, A; Ndiaye, I M; Ndir, O; Ndiaye, D

    2015-12-01

    In developing countries where systemic antifungal are often unavailable, treatment of filamentous fungi infection as Fusarium is sometimes very difficult to treat. We report the case of a keratomycosis due to Fusarium oxysporum treated by povidone iodine eye drops and oral fluconazole. The diagnosis of abscess in the cornea was retained after ophthalmological examination for a 28-year-old man with no previous ophthalmological disease, addressed to the Ophthalmological clinic at the University Hospital Le Dantec in Dakar for a left painful red eye with decreased visual acuity lasting for 15 days. The patient did not receive any foreign body into the eye. Samples by corneal scraping were made for microbiological analysis and the patient was hospitalized and treated with a reinforced eye drops based treatment (ceftriaxone+gentamicin). The mycological diagnosis revealed the presence of a mold: F. oxysporum, which motivated the replacement of the initial treatment by eye drops containing iodized povidone solution at 1% because of the amphotericin B unavailability. Due to the threat of visual loss, oral fluconazole was added to the local treatment with eye drops povidone iodine. The outcome was favorable with a healing abscess and visual acuity amounted to 1/200th. Furthermore, we noted sequels such as pannus and pillowcase. The vulgarization of efficient topical antifungal in developing countries would be necessary to optimize fungal infection treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Effect of an oxygenating agent on oral bacteria in vitro and on dental plaque composition in healthy young adults.

    Science.gov (United States)

    Fernandez y Mostajo, Mercedes; van der Reijden, Wil A; Buijs, Mark J; Beertsen, Wouter; Van der Weijden, Fridus; Crielaard, Wim; Zaura, Egija

    2014-01-01

    Oral bacteria live in symbiosis with the host. Therefore, when mouthwashes are indicated, selective inhibition of taxa contributing to disease is preferred instead of broad-spectrum antimicrobials. The potential selectivity of an oxygenating mouthwash, Ardox-X® (AX), has not been assessed. The aim of this study was to determine the antimicrobial potential of AX and the effects of a twice-daily oral rinse on dental plaque composition. In vitro, 16 oral bacterial strains were tested using agar diffusion susceptibility, minimum inhibitory and minimum bactericidal concentration tests. A pilot clinical study was performed with 25 healthy volunteers. Clinical assessments and microbiological sampling of supragingival plaque were performed at 1 month before the experiment (Pre-exp), at the start of the experiment (Baseline) and after the one-week experimental period (Post-exp). During the experiment individuals used AX mouthwash twice daily in absence of other oral hygiene measures. The microbiological composition of plaque was assessed by 16S rRNA gene amplicon sequencing. AX showed high inter-species variation in microbial growth inhibition. The tested Prevotella strains and Fusobacterium nucleatum showed the highest sensitivity, while streptococci and Lactobacillus acidophilus were most resistant to AX. Plaque scores at Pre-exp and Baseline visits did not differ significantly (p = 0.193), nor did the microbial composition of plaque. During a period of 7-days non-brushing but twice daily rinsing plaque scores increased from 2.21 (0.31) at Baseline to 2.43 (0.39) Post-exp. A significant microbial shift in composition was observed: genus Streptococcus and Veillonella increased while Corynebacterium, Haemophilus, Leptotrichia, Cardiobacterium and Capnocytophaga decreased (p ≤ 0.001). AX has the potential for selective inhibition of oral bacteria. The shift in oral microbiome after 1 week of rinsing deserves further research.

  10. Effect of an oxygenating agent on oral microorganisms in vitro and on dental plaque composition in healthy young adults

    Directory of Open Access Journals (Sweden)

    Mercedes eFernandez y Mostajo

    2014-07-01

    Full Text Available Oral bacteria live in symbiosis with the host. Therefore, when mouthwashes are indicated, selective inhibition of taxa contributing to disease is preferred instead of broad-spectrum antimicrobials. The potential selectivity of an oxygenating mouthwash, Ardox-X® (AX, has not been assessed. The aim of this study was to determine the antimicrobial potential of AX and the effects of a twice-daily oral rinse on dental plaque composition. Material and methods: In vitro, 16 oral bacterial strains were tested using agar diffusion susceptibility, minimum inhibitory and minimum bactericidal concentration tests. A pilot clinical study was performed with 25 healthy volunteers. Clinical assessments and microbiological sampling of supragingival plaque were performed at one month before the experiment (Pre-exp, at the start of the experiment (Baseline and after the one-week experimental period (Post-exp. During the experiment individuals used AX mouthwash twice daily in absence of other oral hygiene measures. The microbiological composition of plaque was assessed by 16S rRNA gene amplicon sequencing. Results: AX showed high inter-species variation in microbial growth inhibition. The tested Prevotella strains and Fusobacterium nucleatum showed the highest sensitivity, while streptococci and Lactobacillus acidophilus were most resistant to AX. Plaque scores at Pre-exp and Baseline visits did not differ significantly (p = 0.193, nor did the microbial composition of plaque during a period of 7-days non-brushing but twice daily rinsing. Plaque scores increased from 2.21 (0.31 at Baseline to 2.43 (0.39 Post-exp. A significant microbial shift in composition was observed: genus Streptococcus and Veillonella increased while Corynebacterium, Haemophilus, Leptotrichia, Cardiobacterium and Capnocytophaga decreased (p ≤ 0.001. Conclusion: AX has the potential for selective inhibition of oral bacteria. The shift in oral microbiome after one week of rinsing deserves

  11. Application of small intestine decompression combined with oral feeding in middle and late period of malignant small bowel obstruction.

    Science.gov (United States)

    Li, Dechun; Du, Hongtao; Shao, Guoqing; Guo, Yongtuan; Lu, Wan; Li, Ruihong

    2017-07-01

    The application value of small intestine decompression combined with oral feeding in the middle and late period of malignant small bowel obstruction was examined. A total of 22 patients with advanced malignant small bowel obstruction were included in the present study. An ileus tube was inserted via the nose under fluoroscopy into the obstructed small intestine of each patient. At the same time, the insertion depth the of the catheter was adjusted. When the catheter was blocked, small bowel selective angiography was performed to determine the location and cause of the obstruction and the extent of the obstruction, and to determine the length of the small intestine in the site of obstruction, and to select the variety and tolerance of enteral nutrition. We observed the decompression tube flow and ease of intestinal obstruction. In total, 20 patients were treated with oral enteral nutrition after abdominal distension, and 22 cases were treated by the nose to observe the drainage and the relief of intestinal obstruction. The distal end of the catheter was placed in a predetermined position. The symptoms of intestinal obstruction were relieved 1-4 days after decompression. The 22 patients with selective angiography of the small intestine showed positive X-ray signs: 18 patients with oral enteral nutrition therapy had improved the nutritional situation 2 weeks later. In 12 cases, where there was anal defecation exhaust, 2 had transient removal of intestinal obstruction catheter. In conclusion, this comprehensive treatment based on small intestine decompression combined with enteral nutrition is expected to become a new therapeutic approach and method for the treatment of patients with advanced tumor small bowel obstruction.

  12. Results of preoperative combined therapy with radiation and multi-drug chemotherapy for oral squamous cell carcinomas

    International Nuclear Information System (INIS)

    Iwai, Masayuki; Sawada, Toshiharu; Furuta, Isao; Sado, Tadashi; Terashima, Ryuichi; Ito, Shigeto

    1996-01-01

    We retrospectively analyzed the effectiveness of preoperative treatment with combined chemotherapy, including cisplatin (CDDP) and carboplatin (CBDCA), and radiotherapy. Among 19 patients with oral squamous cell carcinoma, the primary site was the tongue in 13, the oral floor in 3, and the maxilla, lip, and gingiva in 1 case each. The clinical stage was 7 cases Stage II, 5 cases Stage III, and 7 cases Stage IV. Chemotherapy was administered intravenously using CDDP 50-80 mg (1 time) or CBDCA 150 mg once a week in a total dose of 300-750 mg, PEP 5 mg twice a week in a total dose of 40-60 mg, and 5-FU or Tegaful 300-600 mg in a total dose of 9.0-18.0 g. Radiotherapy was carried out with Lineac (5 times a week) in a total dose of 20-40 Gy/10-20 f/10-20 days. The clinical response to treatment was evaluated as CR 3 cases, PR 9 cases, and NC 6 cases. The response rate was 12/18 (66.7%) cases. Histologic effectiveness, evaluated according to the classification of Oohoshi and Shimosato, was Grade IV 11 cases, Grade III 3 cases, and Grade II 5 cases. The following adverse reactions were reported: stomatitis 19 cases, fever 13 cases, leukopenia 12 cases, loss of appetite 12 cases, and neutropenia 10 cases. Fourteen of the 19 patients (73.7%) have a good prognosis, without any signs of recurrence or metastasis. The results indicate that multidrug chemotherapy combined with radiotherapy is effective even for highly malignant carcinoma in the oral cavity. (author)

  13. Management of Patients with Oral Candidiasis

    DEFF Research Database (Denmark)

    Kragelund, Camilla; Reibel, Jesper; Pedersen, Anne Marie Lynge

    2016-01-01

    Oral candidal infections are medically treated with antifungal agents. In the fungal cell membrane, steroid ergosterol is the target of the antifungals on the market, but similarity with the human cell membrane may cause host toxicity and unintended reactions. Management of oral candidiasis depends...... in particular in patients with recurrent oral candidiasis. This risk can be reduced if different types of antifungal drugs are used over time or are combined. This chapter focuses on antifungal treatment of the medically compromised patient with oral candidiasis by highlighting the advantages and disadvantages...

  14. Combined effect of gamma radiation and some fungal control agents on the greasy cut- worm

    International Nuclear Information System (INIS)

    Abd EL- Wahed, A. G.

    2011-01-01

    The greasy cut worm, Agrotis ipsilon (Lepidoptera- Noctuidae) is widely distributed all over the world, particularly in moderate and subtropical countries of the northern and southern hemispheres (Kononenko ,2003). The greasy cut worm causes damage to vegetables, cucurbitaceous and industrial crops. The greatest damage is caused to cotton, essential-oil cultures, maize, tobacco, sunflower, tomatoes, sugar beet and potato. The pest can strongly harm vegetables, and also damage seedlings of tree species (pine, maple, and nut). This pest has solitary habits. They commonly feed on seedlings at ground level, cutting off the stem and sometimes dragging the plants into their burrows. The continuous use of chemical pesticides against pests, resistance to the action of pesticides had dramatically evolved. Also, the extensive use of these chemicals has given rise to problems such as residual toxicity (pollution) and harmful effects on beneficial insects, which are natural enemies of target or nontarget pest species. Such problems have become a cause of search for safety pesticides including microbial agents as fungi, bacteria and viruses (Rashed, 1993). The use of radiation to induce dominate lethal mutations in the sterile insect technique (SIT) is now as the major component of many large and successful programs for pest suppression and eradication. Adult insects, and their different developmental stages, differ in their sensitivity to the induction of dominate lethal mutation. Care has to be taken to identify the appropriate dose of radiation that produces the required level of sterility without impairing the overall fitness of the released insects.(Sawires, 2005). This technique would be successful control device for suppressing and combating many lepidopteraus insect pests, including A. Ipsilon has been studied (EL- kady et al., 1983, EL-Naggar et al., 1984, Abd El -Hamid 2004 and Gabarty, 2008). Entomopathogenic fungi that infect insects have received considerable

  15. Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein.

    Science.gov (United States)

    Liu, Zulong; Zhu, Hengrui; Qu, Shijin; Tang, Lisha; Cao, Lihuan; Yu, Wenbo; Yang, Xianmei; Jiang, Songmin; Zhu, Dayuan; Tan, Changheng; Yu, Long

    2018-01-01

    Multi-drug resistance (MDR) remains a major impediment in cancer therapy. A major goal for scientists is to discover more effective compounds that are able to circumvent MDR and simultaneously have minimal adverse side effects. In the present study, we aim to determine the anti-MDR effects of pyramidatine (Z88), a cinnamic acid-derived bisamide compound isolated from the leaves of Aglaia perviridis, on KB/VCR (vincristineresistant human oral cancer cells) and MCF-7/ADR (adriamycin-resistant human breast adenocarcinoma) cells. Cell viability and average resistant fold (RF) of Z88 were examined by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry, western blot, RT-PCR, Rhodamine 123 accumulation assay and P-glycoprotein (P-gp) ATPase assay were used to demonstrate the anti-MDR activity and mechanism of Z88. The average RF of Z88 is 0.09 and 0.51 in KB/VCR and MCF-7/ADR cells. A CCK-8 assay showed that Z88 could enhance the cytotoxicity of VCR toward KB/VCR cells. A FACS analysis revealed that Z88 could enhance the VCR-induced apoptosis as well as G2/M arrest in a dose-dependent manner in KB/VCR cells. Western blot results showed that the expression levels of PARP, Bax, and cyclin B1 all increased after treatment with 0.2 µmol/L (µM) of VCR combined with 10 µM of Z88 for 24 h in KB/VCR cells. Z88 also could enhance the accumulation of rhodamine 123. Further studies showed that Z88 could inhibit the verapamil stimulated Pgp ATPase activity. Additionally, qPCR detection and western blot assays revealed that Z88 could decrease the expression of P-gp at both RNA and protein level. Z88 exerted potent anti-MDR activity in vitro and its mechanisms are associated with dualinhibition of the function and expression of P-gp. These findings encourage efforts to develop more effective reversal agents to circumvent MDR based on Z88. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. 14 CFR 399.83 - Unfair or deceptive practice of air carrier, foreign air carrier, or ticket agent in orally...

    Science.gov (United States)

    2010-01-01

    ... TRANSPORTATION (AVIATION PROCEEDINGS) POLICY STATEMENTS STATEMENTS OF GENERAL POLICY Policies Relating to... orally confirming to prospective passenger reserved space on scheduled flights. It is the policy of the... transportation or the sale thereof within the meaning of section 411 of the Act, unless the tariff of the...

  17. Water-equivalent oral contrast agents in dual-modality PET/computed tomography scanning: does a little barium make the difference?

    Science.gov (United States)

    Kinner, Sonja; Veit-Haibach, Patrick; Lauenstein, Thomas C; Bockisch, Andreas; Antoch, Gerald

    2009-03-01

    To retrospectively evaluate the performance of two water-equivalent oral contrast agents [locust bean gum (LBG)-mannitol and VoLumen] concerning their potential to distend the bowel while avoiding contrast-associated artifacts in PET/computed tomography. PET/computed tomography examinations of 30 patients with two different oral contrast agents were reviewed. Bowel distension, intraluminal density, and potential contrast-associated artifacts were assessed for stomach, jejunum, and ileum. Statistical significance was tested by Student's t-test. Distension was slightly better in the stomach with VoLumen as compared with LBG-mannitol whereas LBG-mannitol was found to slightly better distend the small bowel. This difference proved to be statistically significant for the jejunum. A statistically significant difference was detected for intraluminal density with higher densities for VoLumen. This difference, however, did not result in a higher incidence of PET artifacts with VoLumen. LBG-mannitol provides excellent bowel distension, thereby avoiding contrast-associated PET artifacts. If this solution is not available, VoLumen provides a satisfactory alternative for bowel distension without relevant PET artifacts.

  18. Combining Multi-Agent Systems and Wireless Sensor Networks for Monitoring Crop Irrigation

    Directory of Open Access Journals (Sweden)

    Gabriel Villarrubia

    2017-08-01

    Full Text Available Monitoring mechanisms that ensure efficient crop growth are essential on many farms, especially in certain areas of the planet where water is scarce. Most farmers must assume the high cost of the required equipment in order to be able to streamline natural resources on their farms. Considering that many farmers cannot afford to install this equipment, it is necessary to look for more effective solutions that would be cheaper to implement. The objective of this study is to build virtual organizations of agents that can communicate between each other while monitoring crops. A low cost sensor architecture allows farmers to monitor and optimize the growth of their crops by streamlining the amount of resources the crops need at every moment. Since the hardware has limited processing and communication capabilities, our approach uses the PANGEA architecture to overcome this limitation. Specifically, we will design a system that is capable of collecting heterogeneous information from its environment, using sensors for temperature, solar radiation, humidity, pH, moisture and wind. A major outcome of our approach is that our solution is able to merge heterogeneous data from sensors and produce a response adapted to the context. In order to validate the proposed system, we present a case study in which farmers are provided with a tool that allows us to monitor the condition of crops on a TV screen using a low cost device.

  19. Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir.

    Science.gov (United States)

    Johnson, Todd J; Gupta, Kavita M; Fabian, Judit; Albright, Theodore H; Kiser, Patrick F

    2010-02-19

    Dual segment polyurethane intravaginal rings (IVRs) were fabricated to enable sustained release of antiretroviral agents dapivirine and tenofovir to prevent the male to female sexual transmission of the human immunodeficiency virus. Due to the contrasting hydrophilicity of the two drugs, dapivirine and tenofovir were separately formulated into polymers with matching hydrophilicity via solvent casting and hot melt extrusion. The resultant drug loaded rods were then joined together to form dual segment IVRs. Compression testing of the IVRs revealed that they are mechanically comparable to the widely accepted NuvaRing IVR. Physical characterization of the individual IVR segments using wide angle X-ray scattering and differential scanning calorimetry determined that dapivirine and tenofovir are amorphous and crystalline within their polymeric segments, respectively. In vitro release of tenofovir from the dual segment IVR was sustained over 30 days while dapivirine exhibited linear release over the time period. A 90 day accelerated stability study confirmed that dapivirine and tenofovir are stable in the IVR formulation. Altogether, these results suggest that multisegment polyurethane IVRs are an attractive formulation for the sustained vaginal delivery of drugs with contrasting hydrophilicity such as dapivirine and tenofovir. 2009 Elsevier B.V. All rights reserved.

  20. Effect of combined radiotherapy, hyperthermia, radioprotective agent and hypoxic cell sensitizer on mice testes

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Yasuhiko

    1985-08-01

    Application of hyperthermia was executed by immersing pelvis, testes and legs of mice in a thermostatically controlled water bath. Irradiation was carried out using Toshiba KXC-18 type X-ray therapy machine. Mice were killed 30 days after treatment. The testis weights obtained after hypertheramia alone were compared with that of the control and the relative testis weight ratios were calculated. The testis weights of mice treated for 5, 10, 20 and 40 min. in 40 deg C water and for 5 and 10 min. in 43 deg C water were not significantly different from the control. Their weights were reduced when treated for 20 min. in 43 deg C water and for 5 min. in 46 deg C water and their testis weight ratios were 0.81 and 0.46, respectively. The testis weights of irradiated mice decreased to about 45 % of the control at 250 rad. Beyond this dose, reduction of their weights was slowed down and testis weight at 1,000 rad was 28 %. There was not significantly difference between the relative testis weight ratios of the irradiation alone and that of the radiotherapy combined with YM-08310 (S-2-)3-aminopropylamino) ethyl phosphorothioic acid monohydrate). But when hyperthermia was added to their treatment, the effectiveness of the YM-08310 was slightly increased. The relative testis weight ratio on 400 rad X-ray combined with YM-08310 was 0.32 of the control, while its ratio on the radiotherapy and YM-08310 combined with the hyperthermia (43 deg C, 10 min.) was 0.43. (p < 0.01). The misonidazole treatments at 50, 100 and 200 rads were found to be effectuve. Radiation alone gave the relative testis weight ratios of 0.78, 0.71 and 0.49, respectively. In contrast, its ratios on the irradiation combined with the misonidazole were 0.57 (p < 0.01), 0.46 (p < 0.01) and 0.41 (p < 0.001). But, the additional hyperthermia combined with their treatment was found to be ineffective. (J.P.N.).

  1. Combined-modality treatment for advanced oral tongue squamous cell carcinoma

    International Nuclear Information System (INIS)

    Fan, K.-H.; Lin, C.-Y.; Kang, C.-J.; Huang, S.-F.; Wang, H.-M.; Chen, E.Y.-C.; Chen, I.-H.; Liao, C.-T.; Cheng, A.-J.; Chang, J.T.-C.

    2007-01-01

    Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present

  2. Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer

    DEFF Research Database (Denmark)

    Joensuu, H; Holli, K; Heikkinen, M

    1998-01-01

    PURPOSE: We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS: Patients in the single-agent arm...... (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2...... younger than 50. RESULTS: An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity...

  3. The value of a combined word recognition and knowledge measure to understand characteristics of our patients' oral health literacy.

    Science.gov (United States)

    Atchison, Kathryn A; Macek, Mark D; Markovic, Daniela

    2017-08-01

    The objective of the analysis was to examine the association between sociodemographic and dental understanding and utilization characteristics and lower oral health literacy (HL) and knowledge. The cross-sectional Multicenter Oral Health Literacy Research Study (MOHLRS) recruited and interviewed 923 English-speaking, initial care-seeking adults. The questionnaire included participant sociodemographic characteristics, measures of the participant's understanding and utilization of dentistry, and two oral HL measures, the Rapid Estimate of Adult Literacy in Medicine and Dentistry (REALM-D) and the Comprehensive Measure of Oral Health Knowledge (CMOHK), which were combined into a new composite HL and knowledge measure, the MOHLR-K. In adjusted multivariable analysis, persons who reported more understanding of dentist instructions had higher mean scores for all HL measures. Subjects reporting the highest level of understanding had greater scores by an average of 1.6 points for the MOHLR-K (95% CI: 0.85-2.40, Pdental understanding and utilization factors. Persons who reported history of tooth decay had higher MOHLR-K scores by an average of about 0.77 points (95% CI: 0.49-1.04, Ptooth decay history after controlling for the other factors. Persons who had support all of the time for travel to the dentist had higher scores by an average of about 0.5 points for the MOHLR-K (95% CI: 0.04-0.96, P=.03) and about 0.89 points for the REALMD-20 (95% CI: 0-1.79, P=.05) as compared to subjects with no support after controlling for other factors. Report of periodontal history, financial challenges to delay a dental visit and dental utilization were not significantly associated with any of the HL measures once the other factors were adjusted for in the model. The analysis confirmed that pronunciation of medical and dental terms may not fully reflect comprehension and revealed that understanding both patients' sociodemographic and dental understanding and utilization factors, such as

  4. MR of the small bowel with a biphasic oral contrast agent (polyethylene glycol): technical aspects and findings in patients affected by Crohn's disease.

    Science.gov (United States)

    Laghi, Andrea; Paolantonio, Pasquale; Iafrate, Franco; Borrelli, Osvaldo; Dito, Lucia; Tomei, Ernesto; Cucchiara, Salvatore; Passariello, Roberto

    2003-01-01

    To report our experience using MR of the small bowel with polyethylene glycol (PEG) solution as an oral contrast agent in a population of adults and children with known Crohn's disease. 40 patients (29 males; 11 females), 15 adults (age range 24-52 years) and 25 children (age range 5-17 years), with known Crohn's disease, underwent MR of the small bowel using a supeconductive 1.5 T magnet, and polyethylene glycol solution as an oral contrast agent. The fixed amount of contrast agent was 750-1000 ml for adults and 10 ml/kg of body weight for children. The Crohn's Disease Activity Index (CDAI) was available in all patients. Our study protocol included the acquisition of T2-weighted half-Fourier single-shot turbo spin-echo (HASTE) sequences and true fast imaging in the steady-state precession (true-FISP) sequences, followed by the acquisition of "spoiled" 2D gradient echo T1-weighted sequences with fat suppression (FLASH, fast low-angle shot) or alternatively "spoiled" 3D (VIBE, volume interpolated breath-hold examination), acquired 70 seconds after intravenous administration of gadopentetate dimeglumine (Gd-DTPA) (0,1 mmol/kg). A specific MR score was created and calculated for each patient and was compared by means of the Spearman rank with CDAI. In all patients no significant side effects were observed and the MR examination was well tolerated even by paediatric patients. In all cases MR showed a small bowel wall thickening (> 4 mm) in the terminal ileum, with lumen stenosis in 26 patients. In 3 cases pathological segments proximal to the terminal ileum were observed and in another 3 cases caecal involvement was visible. The MR examination was able to show abnormalities of perivisceral fat tissue in 15 patients, mesenteric lymphadenopathy in 1 patient and abdominal abscess in 1 case. The Spearman rank showed a statistically significant correlation between CDAI and the MR score (r = 0.91, P = 0,0001). MR using PEG as an oral contrast agent could be considered a test

  5. Identification of cancer specific ligands from one-bead one compound combinatorial libraries to develop theranostics agents against oral squamous cell carcinoma

    Science.gov (United States)

    Yang, Frances Fan

    Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent disease worldwide. One-bead one-compound (OBOC) combinatorial technology is a powerful method to identify peptidomimetic ligands against a variety of receptors on cell surfaces. We therefore hypothesized that cancer specific ligands against OSCC might be identified and can be conjugated to optical dyes or nanocarriers to develop theranostic agents against OSCC. Material and methods: Different OSCC cell lines were incubated with OBOC libraries and beads with cell binding were sorted and then screened with normal human cells to identify peptide-beads binding to different OSCC cell lines but not binding to normal human cells. The molecular probes of OSCC were developed by biotinylating the carboxyl end of the ligands. OSCC theranostic agents were developed by decorating LLY13 with NPs and evaluated by using orthotopic bioluminescent oral cancer model. Results: Six OSCC specific ligands were discovered. Initial peptide-histochemistry study indicated that LLY12 and LLY13 were able to specifically detect OSCC cells grown on chamber slides at the concentration of 1 muM. In addition, LLY13 was found to penetrate into the OSCC cells and accumulate in the cytoplasm, and nucleus. After screened with a panel of integrin antibodies, only anti-alpha3 antibody was able to block most of OSCC cells binding to the LLY13 beads. OSCC theranostic agents developed using targeting LLY13 micelles (25+/- 4nm in diameter) were more efficient in binding to HSC-3 cancer cells compared to non-targeting micelles. Ex vivo images demonstrated that xenografts from the mice with targeting micelles appeared to have higher signals than the non-targeting groups. Conclusion: LLY13 has promising in vitro and in vivo targeting activity against OSCC. In addition, LLY13 is also able to penetrate into cancer cells via endocytosis. Initial study indicated that alpha3 integrin might partially be the corresponding receptor involved

  6. NP-184[2-(5-methyl-2-furyl) benzimidazole], a novel orally active antithrombotic agent with dual antiplatelet and anticoagulant activities.

    Science.gov (United States)

    Kuo, Heng-Lan; Lien, Jin-Cherng; Chung, Ching-Hu; Chang, Chien-Hsin; Lo, Shyh-Chyi; Tsai, I-Chun; Peng, Hui-Chin; Kuo, Sheng-Chu; Huang, Tur-Fu

    2010-06-01

    The established antiplatelet and anticoagulant agents show beneficial effects in the treatment of thromboembolic diseases; however, these drugs still have considerable limitations. The effects of NP-184, a synthetic compound, on platelet functions, plasma coagulant activity, and mesenteric venule thrombosis in mice were investigated. NP-184 concentration-dependently inhibited the human platelet aggregation induced by collagen, arachidonic acid (AA), and U46619, a thromboxane (TX)A(2) mimic, with IC(50) values of 4.5 +/- 0.2, 3.9 +/- 0.1, and 9.3 +/- 0.5 microM, respectively. Moreover, NP-184 concentration-dependently suppressed TXA(2) formations caused by collagen and AA. In exploring effects of NP-184 on enzymes involved in TXA(2) synthesis, we found that NP-184 selectively inhibited TXA(2) synthase activity with an IC(50) value of 4.3 +/- 0.2 microM. Furthermore, NP-184 produced a right shift of the concentration-response curve of U46619, indicating a competitive antagonism on TXA(2)/prostaglandin H(2) receptor. Intriguingly, NP-184 also caused a concentration-dependent prolongation of the activated partial thromboplastin time (aPTT) with no changes in the prothrombin and thrombin time, indicating that it selectively impairs the intrinsic coagulation pathway. Oral administration of NP-184 significantly inhibited thrombus formation of the irradiated mesenteric venules in fluorescein sodium-treated mice without affecting the bleeding time induced by tail transection. However, after oral administration, NP-184 inhibited the ex vivo mouse platelet aggregation triggered by collagen and U46619 and also prolonged aPTT. Taken together, the dual antiplatelet and anticoagulant activities of NP-184 may have therapeutic potential as an oral antithrombotic agent in the treatment of thromboembolic disorders.

  7. Combined radiation-protective and radiation-sensitizing agents. IV. Measurement of intracellular protector concentrations

    International Nuclear Information System (INIS)

    Koch, C.J.; Stobbe, C.C.; Hettiaratchi, P.

    1989-01-01

    Radiosensitization of hypoxic V79 Chinese hamster cells by 0.5 mM misonidazole at approximately 0-4 degrees C is substantially enhanced by pretreating the cells overnight with 0.1 mM buthionine sulfoximine, which lowers the cellular glutathione content to 5% of control values (from 4 mM to approximately 0.2 mM). The enhanced sensitization is reversed by concentrations of exogenous cysteine that are much lower (0.02 mM) than the original glutathione content. Reduced Co-enzyme A affords reversal of the enhancing effect at concentrations of about 1 mM. Sodium ascorbate gives no protection at all even at concentrations of 2 mM. The intracellular concentration of the reducing agents was measured using a spin-through oil technique. There was no diffusion of Co-A (MW greater than 750) or ascorbate (excluded by charge) into the cells. In contrast, cysteine was rapidly concentrated by factors of 4-10, even at the low temperatures used. Extracellular ascorbate's inability to radioprotect argues against electron transfer across the cell membrane as a mechanism for radioprotection. This mechanism could have explained the ability of exogenous thiols to radioprotect in former studies using glutathione, and in the present studies using Co-A. The potential of cysteine to be concentrated by cells poses a problem in the interpretation of exogenous protection by non-diffusing thiols, since trace contamination by cysteine could lead to the actual protection observed. Cysteine could also be formed by exchange reactions of exogenous thiols with the disulfide of cysteine, present in all media formulations

  8. Effect of antispasmodic agents, alone or in combination, in the treatment of Irritable Bowel Syndrome: Systematic review and meta-analysis

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    M.A. Martínez-Vázquez

    2012-04-01

    Conclusions: Antispasmodics were more effective than placebo in IBS, without any significant adverse events. The addition of simethicone improved the properties of the antispasmodic agents, as seen with the alverine/simethicone and pinaverium/simethicone combinations.

  9. Evaluation of Danazol, Cyclosporine, and Prednisolone as Single Agent or in Combination for Paroxysmal Nocturnal Hemoglobinuria

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    Kanjaksha Ghosh

    2013-12-01

    Full Text Available OBJECTIVE: The responses of 32 patients with paroxysmal nocturnal hemoglobinuria (PNH were assessed after the patients were put on various combinations of danazol, prednisolone, and cyclosporine. METHODS: Nineteen males and 13 females aged between 14 and 60 years with confirmed diagnosis of PNH were treated with danazol (4, danazol + cyclosporine (7, cyclosporine (1, and prednisolone + danazol (20. Response to these interventions was assessed regularly. Danazol was added to cyclosporine in patients with aplastic bone marrow after 3 months of cyclocporine use only unless the former therapy was successful. Four patients with aplastic marrow received only danazol because they had renal insufficiency at presentation. Patients were evaluated with regular complete blood count and routine liver and renal function tests. RESULTS: One patient responded to cyclosporine only. Thirteen of 32 patients (40% had complete response, 12/32 patients (37% had partial response leading to freedom from red cell transfusion, and 2/32 (7% had no response. Five patients (16% died due to thrombosis or hemorrhage within 3 months of therapy before their response to therapy could be assessed. The median period of review of the cases was 4 years and 6 months. CONCLUSION: Danazol is a useful addition to PNH therapy both in combination with cyclosporine for hypoplastic PNH and with prednisolone for other forms of PNH, and this therapy could be a good alternative where eculizumab and anti-lymphocyte globulin cannot be used for various reasons.

  10. Sporothrix schenckii COMPLEX: SUSCEPTIBILITIES TO COMBINED ANTIFUNGAL AGENTS AND CHARACTERIZATION OF ENZYMATIC PROFILES

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    Daniele Carvalho OLIVEIRA

    2015-08-01

    Full Text Available SUMMARY Sporothrix schenckiiwas reclassified as a complex encompassing six cryptic species, which calls for the reassessment of clinical and epidemiological data of these new species. We evaluated the susceptibility of Sporothrix albicans (n = 1 , S. brasiliensis (n = 6 , S. globosa (n = 1, S. mexicana(n = 1 and S. schenckii(n = 36 to terbinafine (TRB alone and in combination with itraconazole (ITZ, ketoconazole (KTZ, and voriconazole (VRZ by a checkerboard microdilution method and determined the enzymatic profile of these species with the API-ZYM kit. Most interactions were additive (27.5%, 32.5% and 5% or indifferent (70%, 50% and 52.5% for TRB+KTZ, TRB+ITZ and TRB+VRZ, respectively. Antagonisms were observed in 42.5% of isolates for the TRB+VRZ combination. Based on enzymatic profiling, the Sporothrix schenckii strains were categorized into 14 biotypes. Leucine arylamidase (LA activity was observed only for S. albicans and S. mexicana. The species S. globosaand S. mexicanawere the only species without β-glucosidase (GS activity. Our results may contribute to a better understanding of virulence and resistance among species of the genus Sporothrixin further studies.

  11. Sporothrix schenckii COMPLEX:SUSCEPTIBILITIES TO COMBINED ANTIFUNGAL AGENTS AND CHARACTERIZATION OF ENZYMATIC PROFILES.

    Science.gov (United States)

    Oliveira, Daniele Carvalho; de Loreto, Érico Silva; Mario, Débora Alves Nunes; Lopes, Paulo G Markus; Neves, Louise Vignolles; da Rocha, Marta Pires; Santurio, Janio Morais; Alves, Sydney Hartz

    2015-01-01

    Sporothrix schenckii was reclassified as a complex encompassing six cryptic species, which calls for the reassessment of clinical and epidemiological data of these new species. We evaluated the susceptibility of Sporothrix albicans(n = 1) , S. brasiliensis(n = 6) , S. globosa(n = 1), S. mexicana(n = 1) and S. schenckii(n = 36) to terbinafine (TRB) alone and in combination with itraconazole (ITZ), ketoconazole (KTZ), and voriconazole (VRZ) by a checkerboard microdilution method and determined the enzymatic profile of these species with the API-ZYM kit. Most interactions were additive (27.5%, 32.5% and 5%) or indifferent (70%, 50% and 52.5%) for TRB+KTZ, TRB+ITZ and TRB+VRZ, respectively. Antagonisms were observed in 42.5% of isolates for the TRB+VRZ combination. Based on enzymatic profiling, the Sporothrix schenckii strains were categorized into 14 biotypes. Leucine arylamidase (LA) activity was observed only for S. albicans and S. mexicana. The species S. globosa and S. Mexicana were the only species without β-glucosidase (GS) activity. Our results may contribute to a better understanding of virulence and resistance among species of the genus Sporothrix in further studies.

  12. Body composition is improved during 12 months' treatment with metformin alone or combined with oral contraceptives compared with treatment with oral contraceptives in polycystic ovary syndrome.

    Science.gov (United States)

    Glintborg, Dorte; Altinok, Magda Lambaa; Mumm, Hanne; Hermann, Anne Pernille; Ravn, Pernille; Andersen, Marianne

    2014-07-01

    Central obesity in polycystic ovary syndrome (PCOS) is associated with increased inflammatory markers and increased risk for type 2 diabetes. The objective of the study was to evaluate whether treatment with metformin (M) or M combined with oral contraceptive pills (OCPs) resulted in a more advantageous body composition than treatment with OCP alone. The study was conducted at an outpatient clinic. This was a randomized, controlled clinical trial. Ninety patients with PCOS were randomized to 12 months' treatment with M (2 g/d), M + OCP (150 mg desogestrel+30 μg ethinylestradiol), or OCP. Whole-body dual-energy x-ray absorptiometry scans and clinical and hormonal evaluations were performed before and after the intervention period. A total of 65 of 90 patients completed the study. Changes in weight at 6 and 12 months and changes in regional fat mass estimates at 12 months were measured. Dropout rates between intervention groups were not significantly different. Treatment with M and M+OCP were superior to OCP regarding weight and regional fat mass. The median (quartiles) weight changes during 12 months of M, M+OCP, and OCP treatment were -3.0 (-10.3; 0.6), -1.9 (-4.9; 0.1), and 1.2 (-0.8; 3.0) kg, respectively, P weight loss and improved body composition compared with OCP, whereas free T levels decreased during M+OCP or OCP. Combined treatment with M+OCP should be considered as an alternative to treatment with OCP alone to avoid weight gain in PCOS.

  13. Oral Presence of Carbohydrate and Caffeine in Chewing Gum: Independent and Combined Effects on Endurance Cycling Performance.

    Science.gov (United States)

    Oberlin-Brown, Katherine T; Siegel, Rodney; Kilding, Andrew E; Laursen, Paul B

    2016-03-01

    The oral presence of carbohydrate (CHO) and caffeine (CAF) may independently enhance exercise performance, but their influence on performance during prolonged exercise is less known. To determine the independent and combined effects of CHO and CAF administered in chewing gum during a cycling time trial (TT) after prolonged exercise. Eleven male cyclists (32.2 ± 7.5 y, 74.3 ± 6.8 kg, 60.2 ± 4.0 mL · kg-1 · min-1 VO2peak) performed 4 experimental trials consisting of 90-min constant-load cycling at 80% of their second ventilatory threshold (207 ± 30 W), followed immediately by a 20-km TT. Under double-blinded conditions, cyclists received placebo (PLA), CHO, CAF, or a combined CHO+CAF chewing gum at 0-, 5-, 10-, and 15-km points of the TT. Overall TT performance was similar across experimental and PLA trials (%mean difference ± 90%CL 0.2% ± 2.0%, 0.4% ± 2.2%, 0.1% ± 1.8% for CHO, CAF, and CHO+CAF). Compared with PLA, mean power output tended to be higher in the first 2 quarters of the TT with CHO (1.6% ± 3.1% and 0.8% ± 2.0%) and was substantially improved in the last 2 quarters during CAF and CHO+CAF trials (4.2% ± 3.0% and 2.0% ± 1.8%). There were no differences in average heart rate (ES performance. Blood lactate was substantially higher post-TT for CAF and CHO+CAF (ES >0.6). After prolonged constant-load cycling, the oral presence of CHO and CAF in chewing gum, independently or in combination, did not improve overall performance but did influence pacing.

  14. Effect of progestin vs. combined oral contraceptive pills on lactation: A double-blind randomized controlled trial

    Science.gov (United States)

    Espey, Eve; Ogburn, Tony; Leeman, Larry; Singh, Rameet; Schrader, Ronald

    2013-01-01

    Objective To estimate the effect of progestin-only vs. combined hormonal contraceptive pills on rates of breastfeeding continuation in postpartum women. Secondary outcomes include infant growth parameters, contraceptive method continuation and patient satisfaction with breastfeeding and contraceptive method. Methods In this randomized controlled trial, postpartum breastfeeding women who desired oral contraceptives were assigned to progestin-only vs. combined hormonal contraceptive pills. At two and eight weeks postpartum, participants completed in-person questionnaires that assessed breastfeeding continuation and contraceptive use. Infant growth parameters including weight, length and head circumference were assessed at eight weeks postpartum. Telephone questionnaires assessing breastfeeding, contraceptive continuation and satisfaction were completed at 3-7 weeks and 4 and 6 months. Breastfeeding continuation was compared between groups using Cox proportional hazards regression. Differences in baseline demographic characteristics and in variables between the two intervention groups were compared using chi-square tests, Fisher’s Exact test, or two-sample t-tests as appropriate. Results Breastfeeding continuation rates, contraceptive continuation, and infant growth parameters did not differ between users of progestin-only and combined hormonal contraceptive pills. Infant formula supplementation and maternal perception of inadequate milk supply were associated with decreased rates of breastfeeding in both groups. Conclusions Choice of combined or progestin-only birth control pills administered two weeks postpartum did not adversely affect breastfeeding continuation. PMID:22143258

  15. Glucan–Resveratrol–Vitamin C Combination Offers Protection against Toxic Agents

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    Jana Vetvickova

    2012-11-01

    Full Text Available Biological immunomodulators are routinely evaluated as a natural source of molecules with profound effects on the immune system. They belong to a group of physiologically active compounds, collectively termed biological response modifiers. Most of the studies were focused on immune system stimulation. Recently, they have become the focus of studies seeking molecules that are able to overcome negative effects of various immunotoxins. This paper concentrates on the effects of a glucan/resveratrol/vitamin C combination on immunosuppressive effects of mercury and perfluorinated hydrocarbons. Effects described in this review have strong clinical potential, as environmental contaminants have adverse effects on all aspects of the immune system and represent a serious threat to the health of both humans and animals.

  16. Effect of alpha-interferon alone and combined with other antineoplastic agents on renal cell carcinoma determined by the tetrazolium microculture assay.

    Science.gov (United States)

    Homma, Y; Aso, Y

    1994-01-01

    The antiproliferative effect of various alpha-interferons (alpha-IFNs), alone or combined with other agents, on a renal cell carcinoma cell line was evaluated by the tetrazolium microculture assay to examine the rationale for combination therapies. Cells incubated in 96-week microculture plates at 5 x 10(3)/well were exposed to various agents for 3 days. There were no obvious differences in the growth inhibition caused by the 5 kinds of alpha-IFN examined as single agents. The combination of alpha-IFN with the following agents was also assessed: 5-fluorouracil (5FU), methotrexate (MTX), mitomycin C, bleomycin, cis-diaminedichloroplatinum (CDDP), vinblastine, etoposide (ETOP), alpha-IFN, tumor necrosis factor-alpha (TNF), and alpha-difluoromethylornithine. Synergism was observed for the combination of alpha-IFN+TNF, while the other combinations had additive or subadditive effects. No interference or antagonism was found. Trimodal combinations of alpha-IFN+MTX with either 5FU, ETOP, or CDDP all showed subadditive effects. These results indicated that an increased antiproliferative effect, although not necessarily synergistic, was obtained by the combination of alpha-IFN with a variety of antineoplastic agents, providing a rationale to seek for combination therapies including alpha-IFN for treating renal cell carcinoma.

  17. Predicting the impact of combined therapies on myeloma cell growth using a hybrid multi-scale agent-based model.

    Science.gov (United States)

    Ji, Zhiwei; Su, Jing; Wu, Dan; Peng, Huiming; Zhao, Weiling; Nlong Zhao, Brian; Zhou, Xiaobo

    2017-01-31

    Multiple myeloma is a malignant still incurable plasma cell disorder. This is due to refractory disease relapse, immune impairment, and development of multi-drug resistance. The growth of malignant plasma cells is dependent on the bone marrow (BM) microenvironment and evasion of the host's anti-tumor immune response. Hence, we hypothesized that targeting tumor-stromal cell interaction and endogenous immune system in BM will potentially improve the response of multiple myeloma (MM). Therefore, we proposed a computational simulation of the myeloma development in the complicated microenvironment which includes immune cell components and bone marrow stromal cells and predicted the effects of combined treatment with multi-drugs on myeloma cell growth. We constructed a hybrid multi-scale agent-based model (HABM) that combines an ODE system and Agent-based model (ABM). The ODEs was used for modeling the dynamic changes of intracellular signal transductions and ABM for modeling the cell-cell interactions between stromal cells, tumor, and immune components in the BM. This model simulated myeloma growth in the bone marrow microenvironment and revealed the important role of immune system in this process. The predicted outcomes were consistent with the experimental observations from previous studies. Moreover, we applied this model to predict the treatment effects of three key therapeutic drugs used for MM, and found that the combination of these three drugs potentially suppress the growth of myeloma cells and reactivate the immune response. In summary, the proposed model may serve as a novel computational platform for simulating the formation of MM and evaluating the treatment response of MM to multiple drugs.

  18. Noncontraceptive use of oral combined hormonal contraceptives in polycystic ovary syndrome-risks versus benefits.

    Science.gov (United States)

    Dokras, Anuja

    2016-12-01

    The use of steroid sex hormones for noncontraceptive benefits has been endorsed by several medical societies. In women with polycystic ovary syndrome (PCOS), hormonal contraceptives are first-line therapy for concurrent treatment of menstrual irregularity, acne, and hirsutism. The association of PCOS with obesity, diabetes, and dyslipidemia frequently brings up the debate regarding risks versus benefits of hormonal contraceptives in this population. In women with PCOS, the lack of large-scale studies evaluating the risks with varying doses of ethinyl estradiol, types of progestins, and presence of confounding factors such as obesity, smoking, and other cardiometabolic comorbidities is a significant limitation in these deliberations. Although it is important to assess the absolute risk for major morbidities including cardiovascular events, currently, there are a paucity of long-term data for these outcomes in PCOS. Most of the current studies do not suggest an increase in risk of prediabetes/diabetes, clinically significant dyslipidemia, inflammatory changes, or depressive/anxiety symptoms with oral contraceptive pill use. Screening of women with PCOS for cardiometabolic and psychiatric comorbidities is routinely recommended. This information should be used by health care providers to individualize the choice of hormonal contraceptive treatment, adequately counsel patients regarding risks and benefits, and formulate an appropriate follow-up plan. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Combined therapy for non-resectable squamous cell carcinoma of the oral cavity

    International Nuclear Information System (INIS)

    Noorman van der Dussen, M.F.

    1986-01-01

    A promising way to acquire information about individual tumour behaviour seems to be the determination of cell kinetic properties and, even more importantly, the changes they undergo during treatment. Ideally, knowledge of changes in cell cycle at all times is desirable so that optimal regulation of the chosen chemotherapy and/or radiotherapy could lead to maximal cell death of the tumour cells with minimal toxicity for the host cells. A possible gain for increasing insight into the characteristics of a particular tumour is DNA flow cytometry. By taking multiple biopsies before and during the chemotherapy/radiotherapy treatment, it is perhaps possible to predict the expected clinical results. Research relating to this is described in this dissertation: 16 patients with non-resectable tumours of the oral cavity were treated with concurrent intra-arterial chemotherapy and radiotherapy. Multiple biopsies were analyzed with DNA flow cytometry and an attempt was made to correlate the clinical response with the acquired cellular kinetic data. The purpose of the research can be summarized as: 1. Is regional cure of non-resectable squamous cell carcinomas possible using the method described? 2. Is it possible, using DNA flow cytometry, to predict the chance of successful therapy? (Auth.)

  20. [Bacteriological study of oral cavity of people of Mexican origin to determine etiology agents of human infections in hand bite].

    Science.gov (United States)

    Cañedo-Guzmán, Cristhyan Baruch; Espinosa-Gutiérrez, Alejandro; Guzmán-Murillo, María Antonia

    2013-01-01

    Hand infections secondary to human bites often leave serious consequences on the functioning of the hand. Such infections are caused by different bacteria. Most bacteriological studies have been made to people of Anglo-Saxon origin or descent, and based on these findings; provide treatment to patients of different origins which may not always be as effective. Descriptive, internal stratified 17 patients were isolated samples of oral cavity and dental plaque bacterial species to identify and define the possible treatment according to the species identified. Microorganisms were isolated Gram (+) and Gram (-) belonging to the normal flora of the oral cavity and dental plaque in all the cases studied, presenting a variable number of microorganisms according to age but not by sex. The group of Gram-positive bacteria isolated showed sensitivity to: erythromycin, chloramphenicol and ciprofloxacin. In the group of Gram negative: kanamycin, amoxicillin + clavulanic acid, ciprofloxacin and norfloxacin, E. Corrodens sensitive to the group of quinolones as ciprofloxacin, norfloxacin as well as ceftriaxone and cefoperazone sulbactam. The bacterial species that are commonly found in normal flora of the oral cavity and dental plaque may be potential pathogens in a hand injury where to find the appropriate conditions for their development.

  1. Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans: an observational cohort study.

    Directory of Open Access Journals (Sweden)

    Daniel P O'Brien

    2012-01-01

    antibiotic treated cases. CONCLUSIONS: Antibiotics combined with surgery may significantly increase treatment success for Mycobacterium ulcerans infections, and fluoroquinolone combined with rifampicin-containing antibiotic regimens can provide an effective and safe oral treatment option.

  2. The role of combined composite resection and irradiation in the management of carcinoma of the oral cavity and oropharynx

    International Nuclear Information System (INIS)

    Wazer, D.E.; Schmidt-Ullrich, R.; Keisch, M.; Karmody, C.S.; Koch, W.

    1989-01-01

    Squamous cell carcinoma of the oral cavity and oropharynx can invade the mandible requiring an 'en bloc' or composite resection. With this procedure alone, reported local control rates for advanced stage tumors have been suboptimal suggesting the need for adjuvant therapy. The treatment records of 35 patients were reviewed who were treated with composite resection alone, composite resection plus radiotherapy, or composite resection as a salvage procedure for a primary treatment failure. Combined irradiation and composite resection resulted in a higher local control than patients receiving composite resection alone (72% vs. 43%). There was no difference in complication rates between these two treatment groups. Composite resection as a salvage procedure resulted in local control in 38% of patients though this was associated with a 64% rate of complications. This data and a review of the literature suggest that tumors of the oral cavity and oropharynx with extension to the mandible requiring composite resection probably represent a category of tumors with a high risk of local recurrence and may benefit from adjuvant irradiation. (orig.) [de

  3. Induction of cytoplasmic petite in yeast by guanidine hydrochloride: combined treatment with other inducing agents.

    Science.gov (United States)

    Villa, L L; Juliani, M H

    1980-06-01

    We have studied the induction of rho- mutants by guanidine hydrochloride (GuHCl) in combination with other known inducers: ethidium bromide (EB), berenil and ultraviolet light. Competition was observed when cells were simultaneously treated with optimal concentrations of EB and GuHCl; on the other hand, treatment of cells with EB in the presence of non-inducing concentrations of GuHCl resulted in the stimulation of rho- induction of EB. Furthermore, using a strain which upon treatment with high EB concentrations shows recovery of respiratory competence, the presence of GuHCl did not interfere either with the early phase of induction or with the recovery phase, but it did interfere in a competitive fashion with the final irreversible phase of EB induction. In the case of berenil, a synergistic effect was seen when cells were pretreated with GuHCl. A synergistic induction was also observed when cells were submitted to UV prior to GuHCl treatment. These results suggest that GuHCl, EB and berenil act via some common step in their rho- induction pathways. Moreover, GuHCl may somehow be decreasing the efficiency of dark repair of ultraviolet lesions on mitochondrial DNA.

  4. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

    Science.gov (United States)

    Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. Thieme Medical Publishers

  5. Application of different types of mandible resection in combined treatment of oral cancer patient (pt.): results and complications

    International Nuclear Information System (INIS)

    Matyakin, E.G.; Uvarov, A.A.; Kropotov, M.A.; Azizjan, R.I.

    1998-01-01

    Surgery is the main part of combined treatment of advanced oral cancer. Three types of mandible resection were applied in our center. Rim mandibulectomy leads to satisfactory cosmetic and functional results, in case of segmental mandibulectomy different methods of mandible restoration are applied. Middle mandibulotomy creates the optimum access to the operation field in patients with a large primary tumor of mobile tongue and a tumor thai is posteriorly located. Aims of the study: analyse of material to estimate the results and complications in cases of application of different types of mandible resection. Conclusions: Segmental mandibulectomy should be performed if erosion of alveolar ridge is detected. Rim manidibulectomy and segmental mandibylectomy with reconstructive surgery lead to good cosmetic and functional results. Usage of mini plates in reconstruction of mandibular arch decrease the number of postoperative complications even in patients after radiation therapy. Previous radiotherapy significantly increase the risk of the postoperative osteomyelitis of mandible

  6. Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

    Science.gov (United States)

    Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

    2011-02-01

    To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

  7. Assessment of the quality of life of elderly with diagnosis of oral squamous cell carcinoma submitted to combined modality therapy

    Directory of Open Access Journals (Sweden)

    Erasmo Bernardo Marinho

    2017-06-01

    Full Text Available Introduction: Evaluating the quality of life allows a more accurate clinical control as well as the provision of prognostic information for specific groups. This study was designed to evaluate the quality of life of elderly diagnosed with oral squamous cell carcinoma submitted to combined modality therapy. Methods: This is a retrospective and observational study, with cross-sectional quantitative character. A total of 206 records of patients with head and neck cancer treated between April 2013 and October 2014 were analyzed. Eleven patients over six months of treatment completion were included in the study. The questionnaire of quality of life of the University of Washington (UW-QOL was applied. The data were collected regarding the social-demographic, clinical-pathological and therapeutic profiles, and the non-stimulated salivary flow was measured. Statistical analysis of quantitative data was performed by the Spearman nonlinear correlation, considering a confidence of 95%. Results: Chewing, saliva and speech showed the lowest scores (31.8; 42.3; 60.6, respectively. Statistically significant correlation was found between: shoulder and mood (r=0.787; swallowing and chewing (r=0.761; completion time of radiotherapy and recreation (r=0.659; activity and recreation (r=0.653; pain and swallowing (r=0.626; chewing and speech (r=0.607; age and speech (r=-0.617. Conclusions: Elderly with oral squamous cell carcinoma diagnosis sunmitted to combined modality therapy presented the areas related to chewing, saliva and speech as the most committed ones. Older individuals have greater impairment of speech, as well as those with longer completion of radiotherapy have better results related to the recreation area.

  8. Prophylactic Use of Oral Acetaminophen or IV Dexamethasone and Combination of them on Prevention Emergence Agitation in Pediatric after Adenotonsillectomy

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    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

  9. MR enterography with oral contrast agent composed of methylcellulose, low-dose barium sulfate, sorbitol, and lactulose: assessment of diagnostic performance, reliability, image quality, and patient tolerance.

    Science.gov (United States)

    Evrimler, Sehnaz; Algin, Oktay

    2016-01-01

    The objective was to show efficiency of magnetic resonance enterography (MRE) with our previously assessed new oral contrast agent. Each bowel segments was evaluated for luminal distension, wall conspicuity, wall thickening, and hyperintensity on fat-saturated (FS) T2-weighted and contrast enhancement on postcontrast FS T1-weighted images. Also, consensus scoring results of MRE exams were compared with the gold standard tests in terms of active inflammatory bowel disease detection. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MRE for active inflammatory bowel disease detection were 62%, 98%, 80%, 96%, and 71.4%, respectively. MRE obtained with the new mixture has a high reliability and shows good correlation with endoscopic examination±biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Recolonization of the oral cavity by Streptococcus mutans after a combined mechanical/chemical antisepsis protocol.

    Science.gov (United States)

    Farina, R; Squarzoni, M A; Calura, G; Trombelli, L

    2009-06-01

    The bacterial colonization of teeth by Streptococcus mutans (StrepM) represents a major risk factor for the development of dental caries. At present, no clinical studies have explored the effect of a combined mechanical-chemical antisepsis protocol in a periodontally-healthy population and the pattern of recolonization of StrepM in subjects whose StrepM infection was successfully eradicated. The present study was designed in order to 1) determine the salivary and plaque changes in StrepM content after a combined mechanical/chemical antisepsis protocol; and 2) evaluate the pattern of recolonization when StrepM was successfully eradicated from saliva and plaque. Thirty-five periodontally-healthy and caries-susceptible subjects successfully entered and concluded the study. At baseline, non-surgical periodontal therapy was performed according to the principles of full mouth disinfection. Adjunctive home-based rinsing with a 0.2% chlorhexidine mouthrinse was requested for the following week. StrepM concentration was assessed in saliva and plaque at the initial contact appointment, at baseline, and 1-week, 1-month, 3-month and 6-month follow-up. A significant effect of ''time'' on StrepM concentration in saliva and plaque was observed (P<0.000). In subjects with successful eradication of StrepM at 1 week (N=17 plaque samples), StrepM infection recurrence occurred within 3-6 months. The results of the present study demonstrated that 1) the application of the investigated mechanical/chemical antisepsis protocol can effectively reduce StrepM colonies in saliva and plaque of periodontally healthy subjects; and 2) in plaque samples, StrepM infection recurrence tends to occur within 3-6 months.

  11. Tamsulosin Monotherapy versus Combination Therapy with Antibiotics or Anti-Inflammatory Agents in the Treatment of Chronic Pelvic Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Tae Hyo Kim

    2011-06-01

    Full Text Available Purpose Chronic pelvic pain syndrome (CPPS is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS. Methods Patients (n=107 who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A, tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B or tamsulosin at 0.2 mg plus antibiotics (group C daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI and the International Prostate Symptom Score (IPSS to evaluate 100 patients who were treated for 12 weeks (7 withdrew. Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL. Results All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05. There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01. Conclusions Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.

  12. Oral estrogen retains potency as an aversion agent in eggs: implications to studies of community ecology and wildlife management.

    Science.gov (United States)

    Nicolaus, L K; Crowe, M; Lundquist, R

    1992-06-01

    The first of two experiments with laboratory rats demonstrated that oral estrogen (17 alpha-ethinylestradiol) can remain in the albumen of eggs at room temperature for up to 8 days with undiminished capacity to produce conditioned taste aversion. The second experiment showed that estrogen remains potent in the yolk of eggs for at least 4 days. There is now greater assurance that egg prey placed into the field will induce reliable CTA among mammalian predators. Community ecologists interested in such processes as competitive release and the responses of prey populations to reduced predation upon their eggs can selectively factor predation out of field experiments without the need for physically excluding predators. Wildlife biologists interested in reducing predation upon the eggs of endangered species now have greater assurance that estrogen-treated egg baits will suppress predation in a more cost-effective manner and with less likelihood of discrimination between treated eggs and those of endangered species.

  13. Evaluation of the palatabilities in 10 different famotidine orally disintegrating tablets by combination of disintegration device and taste sensor.

    Science.gov (United States)

    Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Uchida, Takahiro

    2015-01-01

    The purpose of this study was to evaluate the palatabilities of the original and nine generic versions of famotidine orally disintegrating tablets (FODTs) by means of disintegration times and bitterness intensities determined using in combination disintegration device and taste sensor comparison of human gustatory sensation tests. The disintegration times were determined using a new disintegration testing equipment for ODTs, the OD-mate and bitterness intensities were determined using the SA501C taste-sensing system. The disintegration time and bitterness of each FODT was evaluated in gustatory sensation tests. There was a good correlation between the disintegration times of 10 FODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of FODTs at 10, 20 and 30 s after starting the disintegration using the OD-mate and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. A combination of the OD-mate and the SA501C was capable of predicting the palatabilities, disintegration properties and bitterness intensity of FODTs.

  14. The prophylactic effect of neck irradiation combined with intra-oral electron beam irradiation for early tongue cancer

    International Nuclear Information System (INIS)

    Kawamori, Jiro; Kamata, Rikisaburo; Sanuki, Eiichi

    1993-01-01

    Between 1967 and 1988, 102 patients with Stage T1-2N0 squamous cell carcinoma of the tongue were treated with uneven fractional irradiation therapy (intra-oral electron beam irradiation with and without prophylactic ipsilateral upper neck irradiation at the Dept. of Radiology, Nihon University School of Medicine. Of 102 primary lesions, 89 cases were controlled with this therapy. In this study, these 89 cases were investigated in order to analyze the prophylactic effect of upper neck irradiation. Of the 89 patients, 42 received only intra-oral electron beam irradiation, while the remaining 47 received a combination of intra-oral electron beam irradiation and prophylactic irradiation to the ipsilateral upper neck. Twenty three of the 89 (25.8%) developed metastasis to the neck after the radiotherapy. A breakdown of these 23 cases reveals that 3/21 (14.3%) received 40-50 Gy to the neck, 9/26 (34.6%) received 20-40 Gy to the neck, and 11/42 (26.2%) received no irradiation to the neck (p<0.05 between first and second groups, and between first and third groups). The neck metastasis was classified into one of three categories based on the region in which it first appeared (ipsilateral upper neck, ipsilateral lower neck or contralateral neck). The first metastasis was seen in the ipsilateral upper neck, in the ipsilateral lower neck and in the contralateral neck in 17, 4 and 2 patients, respectively. In 1/19 who had received 40-50 Gy, in 5/21 who had received 20-40 Gy and in 11/42 who had not received neck irradiation the first metastasis appeared in the ipsilateral upper neck. The five year survival rate was 94%, 75% and 85% in the patients receiving 40-50 Gy, 20-40 Gy and no neck irradiation, respectively. These results suggest that prophylactic irradiation of 40-50 Gy to the ipsilateral upper neck might decrease the incidence of neck metastasis and slightly prolong survival time. (author)

  15. Impact of high-flux haemodialysis on the probability of target attainment for oral amoxicillin/clavulanic acid combination therapy.

    Science.gov (United States)

    Hui, Katrina; Patel, Kashyap; Kong, David C M; Kirkpatrick, Carl M J

    2017-07-01

    Clearance of small molecules such as amoxicillin and clavulanic acid is expected to increase during high-flux haemodialysis, which may result in lower concentrations and thus reduced efficacy. To date, clearance of amoxicillin/clavulanic acid (AMC) during high-flux haemodialysis remains largely unexplored. Using published pharmacokinetic parameters, a two-compartment model with first-order input was simulated to investigate the impact of high-flux haemodialysis on the probability of target attainment (PTA) of orally administered AMC combination therapy. The following pharmacokinetic/pharmacodynamic targets were used to calculate the PTA. For amoxicillin, the time that the free concentration remains above the minimum inhibitory concentration (MIC) of ≥50% of the dosing period (≥50%ƒT >MIC ) was used. For clavulanic acid, the time that the free concentration was >0.1 mg/L of ≥45% of the dosing period (≥45%ƒT >0.1 mg/L ) was used. Dialysis clearance reported in low-flux haemodialysis for both compounds was doubled to represent the likely clearance during high-flux haemodialysis. Monte Carlo simulations were performed to produce concentration-time profiles over 10 days in 1000 virtual patients. Seven different regimens commonly seen in clinical practice were explored. When AMC was dosed twice daily, the PTA was mostly ≥90% for both compounds regardless of when haemodialysis commenced. When administered once daily, the PTA was 20-30% for clavulanic acid and ≥90% for amoxicillin. The simulations suggest that once-daily orally administered AMC in patients receiving high-flux haemodialysis may result in insufficient concentrations of clavulanic acid to effectively treat infections, especially on days when haemodialysis occurs. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  16. Comparison of efficacy combination oral terbinafine pulse-dosed and topical 8% ciclopirox olamine with terbinafine monotherapy for onychomycosis: An evidence-based case report

    Directory of Open Access Journals (Sweden)

    Marsha Bianti

    2017-08-01

    Full Text Available Background: Onychomycosis is a fungal infection of the nails, which manifested as nail discoloration, thickening, and detachment from the nail bed. It is not life-threatening, however inappropriate treatment of onychomycosis might lead to complications and affect the patient’s quality of life; making the management of the disease a challenge for clinicians. Objective: Investigate the efficacy of pulse-dosed oral terbinafine combined with topical 8% ciclopirox olamine to treat onychomycosis. Methods: Literature search was performed in Pubmed and Cochrane databases using the keywords 'combination' AND 'oral terbinafine' AND 'ciclopirox' AND ‘onychomycosis treatment’ along with their synonyms and related terms. Results and Discussion: After critical appraisal, studies by Avner et al. and Jaiswal et al. found to be valid, important, and applicable to the patient. The first study found that oral terbinafine combined with topical 8% ciclopirox olamine is more effective and safe compared to terbinafine as a monotherapy (p0.05. Conclusions: Oral terbinafine combined with topical 8% ciclopirox olamine is more effective than monotherapy, despite statistical irrelevance in one of the studies appraised. Further studies are needed to support the implementation of combination therapy.

  17. Synthesis of silver nanoparticles using Dioscorea bulbifera tuber extract and evaluation of its synergistic potential in combination with antimicrobial agents.

    Science.gov (United States)

    Ghosh, Sougata; Patil, Sumersing; Ahire, Mehul; Kitture, Rohini; Kale, Sangeeta; Pardesi, Karishma; Cameotra, Swaranjit S; Bellare, Jayesh; Dhavale, Dilip D; Jabgunde, Amit; Chopade, Balu A

    2012-01-01

    Development of an environmentally benign process for the synthesis of silver nanomaterials is an important aspect of current nanotechnology research. Among the 600 species of the genus Dioscorea, Dioscorea bulbifera has profound therapeutic applications due to its unique phytochemistry. In this paper, we report on the rapid synthesis of silver nanoparticles by reduction of aqueous Ag(+) ions using D. bulbifera tuber extract. Phytochemical analysis revealed that D. bulbifera tuber extract is rich in flavonoid, phenolics, reducing sugars, starch, diosgenin, ascorbic acid, and citric acid. The biosynthesis process was quite fast, and silver nanoparticles were formed within 5 hours. Ultraviolet-visible absorption spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy, and x-ray diffraction confirmed reduction of the Ag(+) ions. Varied morphology of the bioreduced silver nanoparticles included spheres, triangles, and hexagons. Optimization studies revealed that the maximum rate of synthesis could be achieved with 0.7 mM AgNO(3) solution at 50°C in 5 hours. The resulting silver nanoparticles were found to possess potent antibacterial activity against both Gram-negative and Gram-positive bacteria. Beta-lactam (piperacillin) and macrolide (eryth-romycin) antibiotics showed a 3.6-fold and 3-fold increase, respectively, in combination with silver nanoparticles selectively against multidrug-resistant Acinetobacter baumannii. Notable synergy was seen between silver nanoparticles and chloramphenicol or vancomycin against Pseudomonas aeruginosa, and was supported by a 4.9-fold and 4.2-fold increase in zone diameter, respectively. Similarly, we found a maximum 11.8-fold increase in zone diameter of streptomycin when combined with silver nanoparticles against E. coli, providing strong evidence for the synergistic action of a combination of antibiotics and silver nanoparticles. This is the first report on

  18. Combination of Vessel-Targeting Agents and Fractionated Radiation Therapy: The Role of the SDF-1/CXCR4 Pathway

    International Nuclear Information System (INIS)

    Chen, Fang-Hsin; Fu, Sheng-Yung; Yang, Ying-Chieh; Wang, Chun-Chieh; Chiang, Chi-Shiun; Hong, Ji-Hong

    2013-01-01

    Purpose: To investigate vascular responses during fractionated radiation therapy (F-RT) and the effects of targeting pericytes or bone marrow-derived cells (BMDCs) on the efficacy of F-RT. Methods and Materials: Murine prostate TRAMP-C1 tumors were grown in control mice or mice transplanted with green fluorescent protein-tagged bone marrow (GFP-BM), and irradiated with 60 Gy in 15 fractions. Mice were also treated with gefitinib (an epidermal growth factor receptor inhibitor) or AMD3100 (a CXCR4 antagonist) to examine the effects of combination treatment. The responses of tumor vasculatures to these treatments and changes of tumor microenvironment were assessed. Results: After F-RT, the tumor microvascular density (MVD) was reduced; however, the surviving vessels were dilated, incorporated with GFP-positive cells, tightly adhered to pericytes, and well perfused with Hoechst 33342, suggesting a more mature structure formed primarily via vasculogenesis. Although the gefitinib+F-RT combination affected the vascular structure by dissociating pericytes from the vascular wall, it did not further delay tumor growth. These tumors had higher MVD and better vascular perfusion function, leading to less hypoxia and tumor necrosis. By contrast, the AMD3100+F-RT combination significantly enhanced tumor growth delay more than F-RT alone, and these tumors had lower MVD and poorer vascular perfusion function, resulting in increased hypoxia. These tumor vessels were rarely covered by pericytes and free of GFP-positive cells. Conclusions: Vasculogenesis is a major mechanism for tumor vessel survival during F-RT. Complex interactions occur between vessel-targeting agents and F-RT, and a synergistic effect may not always exist. To enhance F-RT, using CXCR4 inhibitor to block BM cell influx and the vasculogenesis process is a better strategy than targeting pericytes by epidermal growth factor receptor inhibitor

  19. Evaluation of combinations of putative anti-biofilm agents and antibiotics to eradicate biofilms of Staphylococcus aureus and Pseudomonas aeruginosa.

    Science.gov (United States)

    Belfield, Katherine; Bayston, Roger; Hajduk, Nadzieja; Levell, Georgia; Birchall, John P; Daniel, Matija

    2017-09-01

    To evaluate potential anti-biofilm agents for their ability to enhance the activity of antibiotics for local treatment of localized biofilm infections. Staphylococcus aureus and Pseudomonas aeruginosa in vitro biofilm models were developed. The putative antibiotic enhancers N-acetylcysteine, acetylsalicylic acid, sodium salicylate, recombinant human deoxyribonuclease I, dispersin B, hydrogen peroxide and Johnson's Baby Shampoo (JBS) were tested for their anti-biofilm activity alone and their ability to enhance the activity of antibiotics for 7 or 14 days, against 5 day old biofilms. The antibiotic enhancers were paired with rifampicin and clindamycin against S. aureus and gentamicin and ciprofloxacin against P. aeruginosa. Isolates from biofilms that were not eradicated were tested for antibiotic resistance. Antibiotic levels 10× MIC and 100× MIC significantly reduced biofilm, but did not consistently eradicate it. Antibiotics at 100× MIC with 10% JBS for 14 days was the only treatment to eradicate both staphylococcal and pseudomonal biofilms. Recombinant human deoxyribonuclease I significantly reduced staphylococcal biofilm. Emergence of resistance of surviving isolates was minimal and was often associated with the small colony variant phenotype. JBS enhanced the activity of antibiotics and several other promising anti-biofilm agents were identified. Antibiotics with 10% JBS eradicated biofilms produced by both organisms. Such combinations might be useful in local treatment of localized biofilm infections. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Comparison of reversal and adverse effects of sugammadex and combination of -Anticholinergic-Anticholinesterase agents in pediatric patients

    Directory of Open Access Journals (Sweden)

    Çiğdem Özgün

    2014-01-01

    Full Text Available Background: We aimed to compare clinical effects of sugammadex versus combination of anticholinergic-anticholinesterase agents for reversing of nondepolarizing neuromuscular block in pediatric patients. Materials and Methods: A total of 60 pediatric patients whom should be performed general anesthesia in the supine position were enrolled to this randomized double-blinded clinical trial. Fentanyl 1 μg/kg, propofol 2 mg/kg, rocuronium 0.6 mg/kg were used in induction and sevofluran, 50% O 2 -50% N 2 O in maintenance of anesthesia. Neuromuscular conductions were assessed by train of four (TOF-Watch SX (Organon, Schering-Plough, Ireland acceleromyograph. Patients were intubated at the moment of TOF 0. At the end of the operation emergence of T2 point was replied by 2 mg/kg sugammadex administration in group 1 and 0.06 mg/kg neostigmine +0.02 mg/kg atropine in group 2. At the moment of T0.9 inhalation, gases were ceased, and patients were extubated. Hemodynamic alterations, access to T0.9, extubation time, recovery parameters, drug consumptions and adverse effects were recorded. Results: Train of four scores showed a lesser increase in group 2 than group 1 from 15 th s to 30 th min during post reverse period (from 6.9 ± 6.4 to 91.7 ± 7.2 in group 2 vs. from 35.4 ± 21.4 to 99.5 ± 1.0 in group 1 (p < 0.0004. Group 1 patients exhibited much more complete muscle strength rates than group 2 (P < 0.001. T0.9 and extubation times were significantly longer in group 2 than group 1 (P < 0.001. Comparison of adverse effects yielded no difference. Conclusion: Sugammadex can be considered as a safe agent in order to reverse neuromuscular block in pediatric patients.

  1. Diabetes mellitus and oral health

    Directory of Open Access Journals (Sweden)

    Đorđević N.

    2015-01-01

    Full Text Available Diabetes mellitus is one of the most common non-communicable chronic diseases, which is the combined action of genetic factors, environmental factors and lifestyle. Specific conditions occur in the oral cavity in the course of diabetes that cause changes in all oral tissues with different symptoms and signs. Increased salivary glucose level is followed by increased accumulation of dental plaque and decreased resistance to noxious agents. The most common oral manifestations in diabetic patients include higher prevalence of periodontal desease, burning mouth syndrome, disruption in salivary flow, opportunistic infections, higher prevalence of denture stomatitis, oral lichen planus, fissured tongue, angular cheilitis etc. Dental interventions in patients with well-controlled diabetes are not different from those applied to nondiabetic patients. Regular monitoring of these patients is required because of the complications that can occur.

  2. Combined use of inactivated and oral poliovirus vaccines in refugee camps and surrounding communities - Kenya, December 2013.

    Science.gov (United States)

    Sheikh, Mohamed A; Makokha, Frederick; Hussein, Abdullahi M; Mohamed, Gedi; Mach, Ondrej; Humayun, Kabir; Okiror, Samuel; Abrar, Leila; Nasibov, Orkhan; Burton, John; Unshur, Ahmed; Wannemuehler, Kathleen; Estivariz, Concepcion F

    2014-03-21

    Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, circulation of indigenous wild poliovirus (WPV) has continued without interruption in only three countries: Afghanistan, Nigeria, and Pakistan. During April-December 2013, a polio outbreak caused by WPV type 1 (WPV1) of Nigerian origin resulted in 217 cases in or near the Horn of Africa, including 194 cases in Somalia, 14 cases in Kenya, and nine cases in Ethiopia (all cases were reported as of March 10, 2014). During December 14-18, 2013, Kenya conducted the first-ever campaign providing inactivated poliovirus vaccine (IPV) together with oral poliovirus vaccine (OPV) as part of its outbreak response. The campaign targeted 126,000 children aged ≤59 months who resided in Somali refugee camps and surrounding communities near the Kenya-Somalia border, where most WPV1 cases had been reported, with the aim of increasing population immunity levels to ensure interruption of any residual WPV transmission and prevent spread from potential new importations. A campaign evaluation and vaccination coverage survey demonstrated that combined administration of IPV and OPV in a mass campaign is feasible and can achieve coverage >90%, although combined IPV and OPV campaigns come at a higher cost than OPV-only campaigns and require particular attention to vaccinator training and supervision. Future operational studies could assess the impact on population immunity and the cost-effectiveness of combined IPV and OPV campaigns to accelerate interruption of poliovirus transmission during polio outbreaks and in certain areas in which WPV circulation is endemic.

  3. Doxorubicin combined with low intensity ultrasound suppresses the growth of oral squamous cell carcinoma in culture and in xenografts

    Directory of Open Access Journals (Sweden)

    Haixia Fan

    2017-11-01

    Full Text Available Abstract Background Oral squamous cell carcinoma (OSCC invades surrounding tissues by upregulating matrix metalloproteinases (MMPs -2 and −9, which causes over-expression of the Hedgehog signaling proteins Shh and Gli-1 and degradation of the extracellular matrix, thereby creating a “highway” for tumor invasion. We explored the potential of low intensity ultrasound (LIUS and doxorubicin (DOX to inhibit the formation of this “highway”. Methods MTT assays were used to examine OSCC cell viability after exposure to LIUS and DOX. The cell morphological changes and ultrastructure were detected by scanning electron microscopy and transmission electron microscopy. Endogenous autophagy-associated proteins were analyzed by immunofluorescent staining and western blotting. Cell migration and invasion abilities were evaluated by Transwell assays. Collagen fiber changes were evaluated by Masson’s trichrome staining. Invasion-associated proteins were analyzed by immunohistochemistry and western blotting. Results LIUS of 1 W/cm2 increased the in vitro DOX uptake into OSCC by nearly 3-fold in three different cell lines and induced transient autophagic vacuoles on the cell surface. The combination of LIUS and 0.2 μg/ml DOX inhibited tumor cell viability and invasion, promoted tumor stromal collagen deposition, and prolonged the survival of mice. This combination also down-regulated MMP-2, MMP-9, Shh and Gli-1 in tumor xenografts. Collagen fiber expression was negatively correlated with the expression of these proteins in human OSCC samples. Conclusions Our findings suggest that effective low dosages of DOX in combination with LIUS can inhibit cell proliferation, migration and invasion, which might be through MMP-2/9 production mediated by the Hedgehog signaling pathway.

  4. Premedication with Oral Alprazolam and Melatonin Combination: A Comparison with Either Alone—A Randomized Controlled Factorial Trial

    Directory of Open Access Journals (Sweden)

    Krishna Pokharel

    2014-01-01

    Full Text Available We assessed if the addition of melatonin to alprazolam has superior premedication effects compared to either drug alone. A prospective, double blind placebo controlled trial randomly assigned 80 adult patients (ASA 1&2 with a Visual Analogue Score (VAS for anxiety ≥3 to receive a tablet containing a combination of alprazolam 0.5 mg and melatonin 3 mg, alprazolam 0.5 mg, melatonin 3 mg, or placebo orally 90 min before a standard anesthetic. Primary end points were change in anxiety and sedation score at 15, 30, and 60 min after premedication, and number of patients with loss of memory for the five pictures shown at various time points when assessed after 24 h. One-way ANOVA, Friedman repeated measures analysis of variance, Kruskal Wallis and chi square tests were used as relevant. Combination drug produced the maximum reduction in anxiety VAS (3 (1.0–4.3 from baseline at 60 min (P<0.05. Sedation scores at various time points and number of patients not recognizing the picture shown at 60 min after premedication were comparable between combination drug and alprazolam alone. Addition of melatonin to alprazolam had superior anxiolysis compared with either drugs alone or placebo. Adding melatonin neither worsened sedation score nor the amnesic effect of alprazolam alone. This study was registered, approved, and released from ClinicalTrials.gov. Identifier number: NCT01486615.

  5. The pharmacokinetics and safety of ABT-751, a novel, orally bioavailable sulfonamide antimitotic agent: results of a phase 1 study.

    Science.gov (United States)

    Hande, Kenneth R; Hagey, Anne; Berlin, Jordan; Cai, Yingna; Meek, Kysa; Kobayashi, Hiro; Lockhart, A Craig; Medina, Diane; Sosman, Jeffrey; Gordon, Gary B; Rothenberg, Mace L

    2006-05-01

    Microtubules play a critical role in many cellular functions, including cell division and mitosis. ABT-751 is a novel sulfonamide antimitotic that binds to the colchicine site on beta-tubulin that leads to a block in the cell cycle at the G2M phase, resulting in cellular apoptosis. ABT-751 was investigated in this phase 1 trial designed to assess its maximum tolerated dose (MTD), dose-limiting toxicity (DLT), tolerability, and pharmacokinetics. ABT-751 was administered on a daily (q.d.) or twice daily (b.i.d.) oral schedule for 7 days every 3 weeks to 39 patients with refractory solid tumors. Toxicity was monitored weekly. Plasma and urine ABT-751 and metabolite pharmacokinetics were determined. The MTD for the q.d. schedule was 250 mg/d. DLTs during cycle 1 were abdominal pain, constipation, and fatigue. The MTD on the b.i.d. schedule was 150 mg. Cycle 1 of therapy with the 175 mg b.i.d. schedule was tolerated without DLT. However, six of seven patients reported grade 3 toxicity (ileus, constipation, abdominal pain, or fatigue), which occurred in cycle 2 or 3. ABT-751 was absorbed after oral administration with an overall mean T(max) of about 2 hours. The pharmacokinetics of ABT-751 were dose-proportional and time-independent. There was minimal accumulation of ABT-751 after multiple q.d. and b.i.d. doses. Efficacious concentrations, as determined from preclinical models (0.5-1.5 microg/mL), were achieved in all subjects. ABT-751 metabolism occurred primarily by glucuronidation and sulfation. No complete or partial tumor responses were noted, but one patient had a minor response, and four patients had stable disease lasting at least 6 months. The MTD and recommended phase 2 doses for ABT-751 were 250 mg q.d. and 150 mg b.i.d. on a 7-day schedule given every 3 weeks, due to subsequent cycle toxicities at 175 mg b.i.d. dosing. Toxicities were abdominal pain, constipation, and neuropathy.

  6. Alternative Oral Agents in Prophylaxis and Therapy of Uterine Fibroids—An Up-to-Date Review

    Directory of Open Access Journals (Sweden)

    Michał Ciebiera

    2017-12-01

    Full Text Available Uterine fibroids (UFs are the most common tumors of the female genital tract. The effect of UFs on the quality of life and the overall cost of treatment are significant issues worldwide. Tumor size and location are the two specific factors which influence the occurrence of symptoms, the need for, and method of, treatment (some tumors require surgery while some can be treated with selected drugs. Primary prevention and treatment of early UF disease are worthy goals that might have a great impact on health care systems. Several treatments and prophylactic methods can be used in this endeavor. This publication presents current data about lesser-known substances which may have a beneficial effect on the treatment or prophylaxis of UFs and can be administered orally, serving as an alternative to (or complement of surgery or selective progesterone receptor modulators (SPRMs. Early prevention and treatment of UFs in women from high-risk groups should be our priority. Innovative forms of UF management are under intensive investigation and may be promising options in the near future. Many of them evaluated vitamin D, paricalcitol, epigallocatechin gallate (EGCG, elagolix, aromatase inhibitors (AIs, and cabergoline and deemed them to be safe and effective. The next step in such projects should be properly constructed randomized control trials (RCTs, carried out by successive phases.

  7. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial

    DEFF Research Database (Denmark)

    Bretzel, R.G.; Nuber, U.; Landgraf, W.

    2008-01-01

    BACKGROUND: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic c...

  8. Efficacy of Acupuncture versus Combined Oral Contraceptive Pill in Treatment of Moderate-to-Severe Dysmenorrhea: A Randomized Controlled Trial

    Science.gov (United States)

    Sriprasert, Intira; Suerungruang, Suparerk; Athilarp, Porntip; Matanasarawoot, Anuchart

    2015-01-01

    This open-label randomized controlled trial was designed to compare the efficacy of acupuncture and combined oral contraceptive (COC) pill in treating moderate-to-severe primary dysmenorrhea. Fifty-two participants were randomly assigned to receive either acupuncture (n = 27) or COC (n = 25) for three menstrual cycles. Mefenamic acid was prescribed as a recue analgesic drug with both groups. The statistical approach used for efficacy and safety assessments was intention-to-treat analysis. By the end of the study, both treatments had resulted in significant improvement over baselines in all outcomes, that is, maximal dysmenorrhea pain scores, days suffering from dysmenorrhea, amount of rescue analgesic used, and quality of life assessed by SF-36 questionnaire. Over the three treatment cycles, COC caused greater reduction in maximal pain scores than acupuncture, while improvements in the remaining outcomes were comparable. Responders were defined as participants whose maximal dysmenorrhea pain scores decreased at least 33% below their baseline. Response rates following both interventions at the end of the study were not statistically different. Acupuncture commonly caused minimal local side effects but did not cause any hormone-related side effects as did COC. In conclusion, acupuncture is an alternative option for relieving dysmenorrhea, especially when COC is not a favorable choice. PMID:26346199

  9. Teaching with technology: learning outcomes for a combined dental and dental hygiene online hybrid oral histology course.

    Science.gov (United States)

    Gadbury-Amyot, Cynthia C; Singh, Amul H; Overman, Pamela R

    2013-06-01

    Among the challenges leaders in dental and allied dental education have faced in recent years is a shortage of well-qualified faculty members, especially in some specialty areas of dentistry. One proposed solution has been the use of technology. At the University of Missouri-Kansas City School of Dentistry, the departure of a faculty member who taught the highly specialized content in oral histology and embryology provided the opportunity to implement distance delivery of that course. The course is taught once a year to a combined group of dental and dental hygiene students. Previous to spring semester of 2009, the course was taught using traditional face-to-face, in-class lectures and multiple-choice examinations. During the spring semesters of 2009, 2010, and 2011, the course was taught using synchronous and asynchronous distance delivery technology. Outcomes for these courses (including course grades and performance on the National Board Dental Examination Part I) were compared to those from the 2006, 2007, and 2008 courses. Students participating in the online hybrid course were also given an author-designed survey, and the perceptions of the faculty member who made the transition from teaching the course in a traditional face-to-face format to teaching in an online hybrid format were solicited. Overall, student and faculty perceptions and student outcomes and course reviews have been positive. The results of this study can provide guidance to those seeking to use technology as one method of curricular delivery.

  10. Polycystic ovary syndrome and combined oral contraceptive use: a comparison of clinical practice in the United States to treatment guidelines.

    Science.gov (United States)

    Bird, Steven T; Hartzema, Abraham G; Etminan, Mahyar; Brophy, James M; Delaney, Joseph A C

    2013-04-01

    The October 2010 ESHRE/ASRM polycystic ovary syndrome (PCOS) workshop concluded: (1) all combined oral contraceptives (COC) appear to have equal efficacy for PCOS, (2) addition of antiandrogens (spironolactone) to COCs has little treatment benefit and (3) metformin does not improve the live-birth rate and should only be used with impaired glucose tolerance. We compared these guidelines to current practice in the United States IMS claims-database. Time-series analyses were conducted by calendar-year in women with PCOS to evaluate prescribing preferences for COCs, concomitant use of spironolactone, and utilization of metformin. Trends were analyzed with linear regression. Our cohort included 1.6 million women taking COCs, 46 780 with a PCOS claim. Drospirenone utilization increased by 1.52% (SE:0.48%, p = 0.007) per-year more in women with PCOS (4.16%, SE:0.45%, p medication management of PCOS to bridge the gap between guidelines and practice.

  11. The clinical effect of combination therapy for oral cancer with S-1, superselective intra-arterial chemotherapy, and radiation therapy

    International Nuclear Information System (INIS)

    Yamamoto, Chika; Yoshikawa, Hiromasa; Fukumoto, Shunsuke; Higuchi, Takashi; Yoshida, Masanori; Yasumori, Koutarou; Horinouchi, Yasufumi; Uehara, Satoru

    2011-01-01

    Combination therapy with S-1, superselective intra-arterial infusion of carboplatin (CBDCA) and radiation therapy has been used to treat patients with oral cancer since 2005. In this study, the histopathological effects and toxicities following concurrent chemoradiotherapy were examined. The subjects consisted of 15 patients (10 men and 5 women) who were treated with S-1 (60-80 mg/day, 4 weeks), superselective intra-arterial infusion of CBDCA (300 mg/body) and radiation therapy (total dose 30-36 Gy) in our department from 2005 to 2009. Nine patients, showed T2 disease, 3 showed T3 disease, and another 3 showed T4 diseases. The primary cancer sites were the tongue (6 cases), buccal mucosa (4 cases), mandible gingival (3 cases), maxillary gingival (1 case), and the floor of the mouth (1 case). The histopathological effects were evaluated according to Oboshi-Shimosato classification. Grade IV was shown in 10 cases (66.7%), grade III in 1 case (6.7%), II bin 3 cases (20.0%), and II a in 1 case (6.7%). All patients completed the treatment. The pathological response of the resected tumor was grade IIb or higher in 14 cases (93.3%). While good histological effects were noted, there was one patient for whom viable tumor cells remained in the central part of the tumor. The present study indicates that further investigation is needed to determine the best dosing and dosing schedule. (author)

  12. Expression profiles of antimicrobial peptides in the genital tract of women using progesterone intrauterine devices versus combined oral contraceptives.

    Science.gov (United States)

    Introini, Andrea; Kaldensjö, Tove; Hirbod, Taha; Röhl, Maria; Tjernlund, Annelie; Andersson, Sonia; Broliden, Kristina

    2014-11-01

    Sex hormones can influence the immune defenses of the female genital tract (FGT) and its susceptibility to infections. Here we investigated the effect of different hormonal contraceptives on the production of antimicrobial peptides (AMPs) in different compartments of the female genital mucosa (FGM), secretions and tissue. Cervicovaginal secretions (CVS) and ectocervical tissue samples obtained from women using progesterone intrauterine devices (pIUD) (n = 23) and combined oral contraceptives (COC) (n = 23) were analyzed for the expression and in situ localization of HNP1-3, BD-2, LL-37, SLPI and trappin-2 by ELISA, real-time PCR and immunohistochemistry. Women using COC had significantly lower mRNA levels of BD-2 and trappin-2 in ectocervical tissue than pIUD users. The two groups showed no differences in CVS concentration, as well as similar in situ expression patterns in ectocervical tissue, of all five AMPs. The use of hormonal contraceptives influences AMP expression differently in genital secretions compared to ectocervical tissue. This suggests that the impact of sex hormones on local immune defenses varies in different compartments of the FGM, and likely in different locations across the FGT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Efficacy of the low-dose combined oral contraceptive chlormadinone acetate/ethinylestradiol: physical and emotional benefits.

    Science.gov (United States)

    Heskamp, Marie-Luise S; Schramm, Georg A K

    2010-01-01

    This study investigated the effects of the low-dose combined oral contraceptive (COC) 2.0 mg chlormadinone acetate (CMA)/0.03 mg ethinylestradiol (EE) (Belara, Balanca) on cycle-related physical and emotional disorders in women >or=25 years of age. A prospective, non-interventional, observational study of 3772 women over six cycles was conducted in 303 office-based gynecological centers throughout Germany. CMA/EE provided high contraceptive efficacy with a Pearl index of 0 (95% confidence interval=0.00-0.22) and was generally well tolerated, with no statistically significant weight changes during the observation period (p=.147). CMA/EE intake resulted in a statistically significant improvement in cycle-related physical and emotional symptoms, with a 67% overall reduction in sum score for number and intensity of cycle-related symptoms per patient. The results of this study in women >or=25 years of age support previous findings that 2.0 mg CMA/0.03 mg EE is an effective low-dose COC, with an excellent tolerability profile, with the additional benefits of significantly reducing both cycle-related physical and emotional symptoms (pcontraceptive treatment. Further research is warranted.

  14. The not-so-bitter pill: Effects of combined oral contraceptives on peripheral physiological indicators of emotional reactivity.

    Science.gov (United States)

    Armbruster, Diana; Kirschbaum, Clemens; Strobel, Alexander

    2017-08-01

    Combined oral contraceptives (COC) are used by millions of women worldwide. Although findings are not entirely consistent, COC have been found to impact on brain function and, thus, to modulate affective processes. Here, we investigated electro-physiological responses to emotional stimuli in free cycling women in both the early follicular and late luteal phase as well as in COC users. Skin conductance response (SCR), startle reflex, corrugator and zygomaticus activity were assessed. COC users showed reduced overall startle magnitude and SCR amplitude, but heightened overall zygomaticus activity, although effect sizes were small. Thus, COC users displayed reduced physiological reactions indicating negative affect and enhanced physiological responses signifying positive affect. In free cycling women, endogenous 17β-estradiol levels were associated with fear potentiated startle in both cycle phases as well as with SCR and zygomaticus activity during the follicular phase. Testosterone was associated with corrugator and zygomaticus activity during the luteal phase, while progesterone levels correlated with corrugator activity in the follicular phase. To the contrary, in COC users, endogenous hormones were not associated with electro-physiological measures. The results further underscore the importance of considering COC use in psychophysiological studies on emotional processing. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer.

    Science.gov (United States)

    Lu, Ya-Ching; Chang, Joseph Tung-Chieh; Huang, Yu-Chen; Huang, Chi-Che; Chen, Wen-Ho; Lee, Li-Yu; Huang, Bing-Shen; Chen, Yin-Ju; Li, Hsiao-Fang; Cheng, Ann-Joy

    2015-02-01

    The aim of this study was to determine whether the oncogenic microRNA family members miR-196a and miR-196b can be circulating biomarkers for the early detection of oral cancer. To determine the stability of circulating miRNA, the blood sample was aliquot and stored at different temperature conditions for analysis. To assess the diagnostic efficacy, we determined the levels of miR-196s in plasma samples, including 53 from healthy individuals, 16 from pre-cancer patients, and 90 from oral cancer patients. In general, circulating miRNA was very stable when storing plasma samples at -20°C or below. In clinical study, both circulating miR-196a and miR-196b were substantially up-regulated in patients with oral pre-cancer lesions (5.9- and 14.8-fold, respectively; P oral cancer patients (9.3- and 17.0-fold, respectively; P cancer patients (AUC = 0.764 or 0.840, miR-196a or miR-196b, respectively), and between normal and cancer patients (AUC = 0.864 or 0.960, miR-196a or miR-196b, respectively). The combined determination of miR-196a and miR-196b levels produces excellent sensitivity and specificity in the diagnosis of patients with oral pre-cancer (AUC = 0.845) or oral cancer (AUC = 0.963), as well as in the prediction of potential malignancy (AUC = 0.950, sensitivity = 91%, specificity = 85%). Combined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Prescription trends and the selection of initial oral antidiabetic agents for patients with newly diagnosed type 2 diabetes: a nationwide study.

    Science.gov (United States)

    Liu, C-H; Chen, S-T; Chang, C-H; Chuang, L-M; Lai, M-S

    2017-11-01

    The aim of this study was to examine the characteristics of patients, physicians, and medical facilities, and their association with prescriptions that do not include metformin as the initial oral antidiabetic agent. Observational, cross-sectional study. Patients with incident type 2 diabetes between January 1, 2006, and December 31, 2010, were identified from the Taiwan National Insurance Research Database. We describe trends in the initial prescription of antidiabetic medications that do not contain metformin during the study period. A multivariable logistic model and a multilevel linear model were used in the analysis of factors at a range of levels (patient, physician, and medical facility), which may be associated with the selection of oral antidiabetic drugs. During the study period, the proportion of prescriptions that did not include metformin declined from 43.8% to 26.2%. Male patients were more likely to obtain non-metformin prescriptions (adjusted odds ratio [OR]: 1.15; 95% confidence interval [CI]: 1.08-1.23), and the likelihood that a patient would be prescribed a non-metformin prescription increased with age. Physicians aged ≥35 years and those with specialties other than endocrinology tended to prescribe non-metformin prescriptions. Metformin was less commonly prescribed in for-profit hospitals (adjusted OR: 1.34, 95% CI: 1.11-1.61) and hospitals in smaller cities (adjusted OR: 1.28, 95% CI: 1.05-1.57) and rural areas (adjusted OR: 1.83, 95% CI: 1.32-2.54). Disparities continue to exist in clinical practice with regard to the treatment of diabetes. These inequalities appear to be linked to a variety of factors related to patients, physicians, and medical facilities. Further study will be required to understand the effects of continuing medical education in enhancing adherence to clinical guidelines. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  17. Synthesis of silver nanoparticles using Dioscorea bulbifera tuber extract and evaluation of its synergistic potential in combination with antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Ghosh S

    2012-02-01

    -positive bacteria. Beta-lactam (piperacillin and macrolide (erythromycin antibiotics showed a 3.6-fold and 3-fold increase, respectively, in combination with silver nanoparticles selectively against multidrug-resistant Acinetobacter baumannii. Notable synergy was seen between silver nanoparticles and chloramphenicol or vancomycin against Pseudomonas aeruginosa, and was supported by a 4.9-fold and 4.2-fold increase in zone diameter, respectively. Similarly, we found a maximum 11.8-fold increase in zone diameter of streptomycin when combined with silver nanoparticles against E. coli, providing strong evidence for the synergistic action of a combination of antibiotics and silver nanoparticles.Conclusion: This is the first report on the synthesis of silver nanoparticles using D. bulbifera tuber extract followed by an estimation of its synergistic potential for enhancement of the antibacterial activity of broad spectrum antimicrobial agents.Keywords: Dioscorea bulbifera tuber extract, silver nanoparticles, antimicrobial synergy

  18. Effectiveness and safety of exenatide in Korean patients with type 2 diabetes inadequately controlled with oral hypoglycemic agents: an observational study in a real clinical practice.

    Science.gov (United States)

    Hwang, You-Cheol; Kim, Ari; Jo, Euna; Yang, Yeoree; Cho, Jae-Hyoung; Lee, Byung-Wan

    2017-10-25

    Randomized clinical trials have shown the efficacy and safety of short-acting exenatide in patients with type 2 diabetes mellitus (T2DM). The aim of this observational study was to investigate the effectiveness and safety of exenatide twice a day in Korean patients with T2DM who are suboptimally controlled with oral hypoglycemic agents. This study was a post hoc analysis of multi-center (71 centers), prospective, observational, single-arm, post-marketing study of short-acting exenatide 5 to 10 μg twice a day from March 2008 to March 2014 and analyzed those who finished the follow-up over 20 weeks of medication. Changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight values before and after exenatide treatment were analyzed. Adverse events and adverse drug reactions were estimated in patients who were treated with exenatide at least once and for whom follow-up for safety has been completed. After 20 weeks treatment with exenatide, mean HbA1c and body weight were significantly reduced from 8.4% to 7.7% and from 83.4 kg to 80.2 kg, respectively (both p levels showed an independent association with a greater reduction in glucose level. In addition, short duration of diabetes less than 5 years was an independent predictor for the improvement in glucose level. The majority of study subjects showed a reduction in both body weight and glucose level (63.3%) after exenatide treatment. In terms of safety profile, exenatide treatment was generally well-tolerated and the incidence of severe adverse event was rare (0.8%). The gastrointestinal side effects were most common and hypoglycemia was reported in 1.7% of subjects. In real clinical practice, 20 weeks treatment with short-acting exenatide was well tolerated and showed a significant body weight and glucose reduction in Korean patients with T2D who are suboptimally controlled with oral hypoglycemic agents. ClinicalTirals.gov , number NCT02090673 , registered 14 February 2008.

  19. A randomized controlled trial of enemas in combination with oral laxative therapy for children with chronic constipation

    NARCIS (Netherlands)

    Bongers, Marloes E. J.; van den Berg, Maartje M.; Reitsma, Johannes B.; Voskuijl, Wieger P.; Benninga, Marc A.

    2009-01-01

    After 5 years of intensive oral laxative use, up to 30% of constipated children still have an unsuccessful outcome. Children refractory to oral laxatives might benefit from regular rectal evacuation by enemas. This randomized controlled trial compared the effects of additional treatment with rectal

  20. Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin.

    Science.gov (United States)

    Truchuelo, M T; Jiménez, N; Mavura, D; Jaén, P

    2015-03-01

    The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. To determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Prospective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. Although the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. This new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

  1. Prescription of oral hypoglycemic agents for patients with type 2 diabetes mellitus: A retrospective cohort study using a Japanese hospital database.

    Science.gov (United States)

    Tanabe, Makito; Motonaga, Ryoko; Terawaki, Yuichi; Nomiyama, Takashi; Yanase, Toshihiko

    2017-03-01

    In treatment algorithms of type 2 diabetes mellitus in Western countries, biguanides are recommended as first-line agents. In Japan, various oral hypoglycemic agents (OHAs) are available, but prescription patterns are unclear. Data of 7,108 and 2,655 type 2 diabetes mellitus patients in study 1 and study 2, respectively, were extracted from the Medical Data Vision database (2008-2013). Cardiovascular disease history was not considered in study 1, but was in study 2. Initial choice of OHA, adherence to its use, effect on glycated hemoglobin levels for 2 years and the second choice of OHA were investigated. In study 1, α-glucosidase inhibitor, glinide and thiazolidinedione were preferentially medicated in relatively lower glycated hemoglobin cases compared with other OHAs. The two most prevalent first prescriptions of OHAs were biguanides and dipeptidyl peptidase-4 inhibitors, and the greatest adherence was for α-glucosidase inhibitors. In patients treated continuously with a single OHA for 2 years, improvement in glycated hemoglobin levels was greatest for dipeptidyl peptidase-4 inhibitors. As a second OHA added to the first OHA during the first 2 years, dipeptidyl peptidase-4 inhibitors were chosen most often, especially if a biguanide was the first OHA. In study 2, targeting patients with a cardiovascular disease history, a similar tendency to study 1 was observed in the first choice of OHA, adherence and the second choice of OHA. Even in Japanese type 2 diabetes mellitus patients, a Western algorithm seems to be respected to some degree. The OHA choice does not seem to be affected by a cardiovascular disease history. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  2. Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis.

    Science.gov (United States)

    Penna, Pete; Meckfessel, Matthew H; Preston, Norman

    2014-01-01

    Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne. The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin. In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of

  3. Combining integrated river modelling and agent based social simulation for river management; The case study of the Grensmaas project

    NARCIS (Netherlands)

    Valkering, P.; Krywkow, Jorg; Rotmans, J.; van der Veen, A.; Douben, N.; van Os, A.G.

    2003-01-01

    In this paper we present a coupled Integrated River Model – Agent Based Social Simulation model (IRM-ABSS) for river management. The models represent the case of the ongoing river engineering project “Grensmaas”. In the ABSS model stakeholders are represented as computer agents negotiating a river

  4. Efficacy and safety of combining intra-articular methylprednisolone and anti-TNF agent to achieve prolonged remission in patients with recurrent inflammatory monoarthritis.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2012-02-01

    OBJECTIVE: To control local inflammation, the role of intra-articular corticosteroid is well established; similarly, with time there are more reports on the experience of intra-articular anti-TNF agent for localized joint inflammation. The aim of this study was to assess the safety, local tolerability and clinical response after combining intra-articular administration of corticosteroids and anti-TNF agents for recurrent inflammatory monoarthritis. METHODS: Patients with recurrent monoarthritis of the knee were recruited from our inflammatory arthritis clinics. These patients required intra-articular corticosteroids every 8-12 weeks, with good short-term results. Five such consecutive patients were invited to partake in this study. Patients were maintained on their baseline immunosuppressive therapy. After aspiration of knee joint, the involved joint was injected with 80mg of methylprednisolone mixed with 5ml of lignocaine 1%; this was followed by the injection of an anti-TNF agent. RESULTS: In majority of our patients (three out of five), combining anti-TNF agent and methylprednisolone led to prolonged anti-inflammatory response, and these patients remain in remission to date (mean follow-up of 12 months). These responders were noted to be naive to anti-TNF therapy. Conversely, the remaining two patients were found to be on baseline systemic anti-TNF therapy, and both of them failed to respond either partly or completely. CONCLUSION: Combining intra-articular corticosteroid and anti-TNF agent has proved to be safe in our cohort of patients. We conclude that in particular subset of patients who suffer from recurrent inflammatory monoarthritis or oligoarthritis, combination therapy of intra-articular corticosteroids and anti-TNF agents appears attractive and promising.

  5. A novel single walled carbon nanotube (SWCNT) functionalization agent facilitating in vivo combined chemo/thermo therapy

    Science.gov (United States)

    Zhang, Liwen; Rong, Pengfei; Chen, Minglong; Gao, Shi; Zhu, Lei

    2015-10-01

    Carbon nanotubes (CNTs) have shown intriguing applications in biotechnological and biomedical fields due to their unique shape and properties. However, the fact that unmodified CNTs are prone to aggregation, stunts CNTs applications under physiological conditions. In this research, we found that as little as 1/5th the single walled carbon nanotube (SWCNT) weight of Evans Blue (EB) is capable of dispersing SWCNT as well as facilitating SWCNT functionalization. In view of the binding between EB and albumin, the yielding product (SWCNT/EB) demonstrated extreme stability for weeks under physiological conditions and it can be endowed with a therapeutic ability by simply mixing SWCNT/EB with an albumin based drug. Specifically, the formed SWCNT/EB/albumin/PTX nanocomplex exhibits strong near-infrared (NIR) absorbance, and can serve as an agent for chemo/thermal therapeutic purposes. Our in vivo result reveals that SWCNT/EB/albumin/PTX after being administered into the MDA-MB-435 tumor would effectively ablate the tumor by chemo and photothermal therapy. Such a combined treatment strategy provides remarkable therapeutic outcomes in restraining tumor growth compared to chemo or photothermal therapy alone. Overall, our strategy of dispersing SWCNTs by EB can be used as a platform for carrying other drugs or functional genes with the aid of albumin to treat diseases. The present study opens new opportunities in surface modification of SWCNTs for future clinical disease treatment.Carbon nanotubes (CNTs) have shown intriguing applications in biotechnological and biomedical fields due to their unique shape and properties. However, the fact that unmodified CNTs are prone to aggregation, stunts CNTs applications under physiological conditions. In this research, we found that as little as 1/5th the single walled carbon nanotube (SWCNT) weight of Evans Blue (EB) is capable of dispersing SWCNT as well as facilitating SWCNT functionalization. In view of the binding between EB and

  6. Case Report: Diagnosis of hypogeusia after oral exposure to commercial cleaning agent and considerations for clinical taste testing [version 2; referees: 2 approved, 1 not approved

    Directory of Open Access Journals (Sweden)

    Marie Jetté

    2017-06-01

    Full Text Available Few reports in the literature document acute taste disturbance following exposure to toxic chemicals. We describe the case of a 54-year-old man who presented with primary complaint of tongue numbness and persistent problems with taste 1.5 years following oral exposure to a commercial cleaning agent. A test of olfaction revealed normosmia for age and gender. Lingual tactile two-point discrimination testing showed reduced somatosensation. Taste threshold testing using a 3-drop method demonstrated severe hypogeusia, though the patient was able to discriminate tastants at lower concentrations with a whole mouth swish and spit test. We conclude that clinical evaluation of dysgeusia can be performed using a number of previously published testing methods, however, determining causative factors may be confounded by duration since exposure, lack of knowledge of baseline taste function, and medications. Although many testing options exist, basic taste testing can be performed with minimal expertise or specialized equipment, depending on the patient history and goals of evaluation.

  7. Anti-inflammation of the oral mucous after radiotherapy of side effect to the propolis combined effect

    Energy Technology Data Exchange (ETDEWEB)

    Takenori, Yamashita; Gu, Yeunhwa; Park, Sangrae [Suzuka Univ. of Medical Science, Suzuka (Japan)] [and others

    2002-07-01

    Recently, allege acid sodium (AL-G) that affect is proved in the bleeding digestion pipe tumor, the effect on treatment for wound such as a radiation esophagus flame because of the inflammation reduction inside such a mouth is used. Because a tumor and an inflammation are effective, propolis to use for this research is the purpose of examining the anti-inflammation action of the mucous membrane flame in the mouth. The inside of the mouth was made to contain each medicine, and effect on organization repair was examined from the viewpoint of study of the organization. An ICR mail mice used at age of seven weeks. Feed and water were taken freely. As for the experiment group, 2Gy, 4Gy, 8Gy irradiated each of the control group, the oral part separately. Two times gave it 2Gy, 4Gy and 8Gy group, AL-G, a physiology solution of salt, propolis combination thing (Propolis + royal jelly (RJ) +EF2001), PVP in the morning. We used in each groups of 10 mail mice AL-G+2G, AL-G+4GyAL-G+8Gy, Saline+2Gy, Saline+4Gy, Saline+8Gy,Propolis+(RJ+EF2001)+2Gy,Propolis+ (RJ+EF2001)+4Gy,Propolis+(RJ+EF2001)+8Gy, PVP+2Gy, PVP+4Gy and PVP+8Gy groups. It was divided into each group of 2Gy, 4Gy and 8Gy groups from the bottom part of the ear of the ICR mice by the nose head, and it irradiated it once.

  8. Anti-inflammation of the oral mucous after radiotherapy of side effect to the propolis combined effect

    International Nuclear Information System (INIS)

    Takenori, Yamashita; Gu, Yeunhwa; Park, Sangrae

    2002-01-01

    Recently, allege acid sodium (AL-G) that affect is proved in the bleeding digestion pipe tumor, the effect on treatment for wound such as a radiation esophagus flame because of the inflammation reduction inside such a mouth is used. Because a tumor and an inflammation are effective, propolis to use for this research is the purpose of examining the anti-inflammation action of the mucous membrane flame in the mouth. The inside of the mouth was made to contain each medicine, and effect on organization repair was examined from the viewpoint of study of the organization. An ICR mail mice used at age of seven weeks. Feed and water were taken freely. As for the experiment group, 2Gy, 4Gy, 8Gy irradiated each of the control group, the oral part separately. Two times gave it 2Gy, 4Gy and 8Gy group, AL-G, a physiology solution of salt, propolis combination thing (Propolis + royal jelly (RJ) +EF2001), PVP in the morning. We used in each groups of 10 mail mice AL-G+2G, AL-G+4GyAL-G+8Gy, Saline+2Gy, Saline+4Gy, Saline+8Gy,Propolis+(RJ+EF2001)+2Gy,Propolis+ (RJ+EF2001)+4Gy,Propolis+(RJ+EF2001)+8Gy, PVP+2Gy, PVP+4Gy and PVP+8Gy groups. It was divided into each group of 2Gy, 4Gy and 8Gy groups from the bottom part of the ear of the ICR mice by the nose head, and it irradiated it once

  9. Metabolic Effects of a Commonly Used Combined Hormonal Oral Contraceptive in Women With and Without Polycystic Ovary Syndrome

    Science.gov (United States)

    Adeniji, Adeola A.; Essah, Paulina A.; Nestler, John E.

    2016-01-01

    Abstract Background: Data on combined hormonal oral contraceptives' (OCs) effects on metabolic changes in women with polycystic ovary syndrome (PCOS) have been conflicting and were predominantly based on OCs with cyproterone acetate (unavailable in the United States) Most studies did not include normal women as controls. We compared metabolic changes before and after an OC commonly used in the United States between women with and without PCOS. Methods: Ten PCOS and 20 control women took ethinyl estradiol 35 μg and norgestimate 0.18/0.215/0.25 mg. Fasting glucose and insulin, area-under-the-curve (AUC) glucose and insulin, insulin sensitivity (homeostatic model assessment of insulin sensitivity index [HOMA-ISI] and Matsuda index), insulinogenic index (Δinsulin0–30 minutes/Δglucose0–30 minutes), blood pressure, and lipids were evaluated at baseline and after three cycles of OC. Results: At baseline, PCOS women had lower insulin sensitivity (Matsuda index p = 0.0093, HOMA-ISI p = 0.0397), higher fasting insulin (p = 0.0495), fasting glucose (p = 0.0393), AUC insulin (p = 0.0023), and triglycerides (p = 0.0044) versus controls. Baseline AUC glucose did not differ between PCOS women and controls. After 3 months of OC use, glucose tolerance worsened in PCOS women versus controls (p = 0.0468). Higher baseline androgens were predictive of worsened glucose tolerance, and a reduction of AUC insulin during OC use. The insulinogenic index significantly decreased in PCOS women (p glucose tolerance (demonstrated by AUC glucose) after 3 months of a commonly used OC compared with control women. Larger studies with longer follow-up should confirm these findings. PMID:26871978

  10. DOT1L inhibitor EPZ-5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLL-rearranged leukemia cells.

    Science.gov (United States)

    Klaus, Christine R; Iwanowicz, Dorothy; Johnston, Danielle; Campbell, Carly A; Smith, Jesse J; Moyer, Mikel P; Copeland, Robert A; Olhava, Edward J; Scott, Margaret Porter; Pollock, Roy M; Daigle, Scott R; Raimondi, Alejandra

    2014-09-01

    EPZ-5676 [(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol], a small-molecule inhibitor of the protein methyltransferase DOT1L, is currently under clinical investigation for acute leukemias bearing MLL-rearrangements (MLL-r). In this study, we evaluated EPZ-5676 in combination with standard of care (SOC) agents for acute leukemias as well as other chromatin-modifying drugs in cellular assays with three human acute leukemia cell lines: MOLM-13 (MLL-AF9), MV4-11 (MLL-AF4), and SKM-1 (non-MLL-r). Studies were performed to evaluate the antiproliferative effects of EPZ-5676 combinations in a cotreatment model in which the second agent was added simultaneously with EPZ-5676 at the beginning of the assay, or in a pretreatment model in which cells were incubated for several days in the presence of EPZ-5676 prior to the addition of the second agent. EPZ-5676 was found to act synergistically with the acute myeloid leukemia (AML) SOC agents cytarabine or daunorubicin in MOLM-13 and MV4-11 MLL-r cell lines. EPZ-5676 is selective for MLL-r cell lines as demonstrated by its lack of effect either alone or in combination in the nonrearranged SKM-1 cell line. In MLL-r cells, the combination benefit was observed even when EPZ-5676 was washed out prior to the addition of the chemotherapeutic agents, suggesting that EPZ-5676 sets up a durable, altered chromatin state that enhances the chemotherapeutic effects. Our evaluation of EPZ-5676 in conjunction with other chromatin-modifying drugs also revealed a consistent combination benefit, including synergy with DNA hypomethylating agents. These results indicate that EPZ-5676 is highly efficacious as a single agent and synergistically acts with other chemotherapeutics, including AML SOC drugs and DNA hypomethylating agents in MLL-r cells. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Oral cancer.

    Science.gov (United States)

    Gerson, S J

    1990-01-01

    In the U.S. oral cancer accounts for 2.1% of all cancers and 1% of cancer deaths. Two to three times as many males as females are affected. Blacks have more intra-oral cancer than whites, and their incidence and mortality rates have increased in recent years. The etiologic process very likely involves several factors. The major etiologic agents are tobacco (all types) and alcoholic beverages. Herpes simplex virus, human papilloma virus, and Candida have been implicated. Host factors include poor state of dentition, nutritional aberrations, cirrhosis of liver, lichen planus, and immunologic impairmant. Cellular changes include amplification of some oncogenes, alterations in antigen expression, production of gamma-glutamyl transpeptidase, and disturbance of keratin and involucrin production. Experimentally, cancer is readily produced on the hamster cheek pouch and rat oral mucosa. Unlike oral cancer in humans, most experimental lesions are exophytic, and they rarely metastasize.

  12. Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus.

    Science.gov (United States)

    Yew, Yik Weng; Pan, Jiun Yit

    2014-01-01

    Genital warts in immunocompromised patients can be extensive and recalcitrant to treatment. We report a case of recalcitrant genital warts in a female patient with systemic lupus erythematosus (SLE), who achieved complete remission with a combination approach of surgical debulking and oral isotretinoin at an initial dose of 20 mg/day with a gradual taper of dose over 8 months. She had previously been treated with a combination of topical imiquimod cream and regular fortnightly liquid nitrogen. Although there was partial response, there was no complete clearance. Her condition worsened after topical imiquimod cream was stopped because of her pregnancy. She underwent a combination approach of surgical debulking and oral isotretinoin after her delivery and achieved full clearance for more than 2 years duration. Oral isotretinoin, especially in the treatment of recalcitrant genital warts, is a valuable and feasible option when other more conventional treatment methods have failed or are not possible. It can be used alone or in combination with other local or physical treatment methods. © 2013 Wiley Periodicals, Inc.

  13. Clinical application of oral form of ANGIPARSTM and in combination with topical form as a new treatment for diabetic foot ulcers: A randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Bahrami A

    2008-04-01

    Full Text Available ANGIPARSTM is a new herbal extract which has been produced in oral, topical, and intravenous forms. The present article contains preliminary results of the study which was planned to evaluate the efficacy and safety of orally applied ANGIPARSTM and to compare it with the combination of oral and topical forms and also with conventional therapy in patients with diabetic ulcers of the lower extremities."nTwenty one patients with diabetic foot ulcers were divided into 3 groups. The first group received 100 mg of oral ANGIPARSTM twice a day for 6 weeks in addition to conventional therapies. In the second group, ANGIPARSTM gel 3% was added to the oral form of the same product besides the conventional therapies for the same period of time. Finally, in the third group which was considered as control, only conventional therapies were performed. The patients were followed for 6 weeks. Parameters such as granulation tissue formation, skin epithelization, and wound surface areas changes were analyzed to determine the effectiveness of the compound in wounds healing. Furthermore, drug safety was assessed by monitoring adverse events and by clinical and laboratory evaluations."nThe study data showed significant differences between the intervention and control groups with respect to efficacy and tolerability. In each intervention group, primary wound healings occurred following 2 weeks. Complete wound healing which was greater than 70% improvement in wounds surface areas was achieved in 83% and 100% of group 1 and group 2 participants, respectively after 6 weeks. On the other hand, at the same period of time, only 22.2% of patients in control group revealed complete healing. Therefore, ANGIPARSTM had significant positive effect in increasing the incidence of complete wound closure compared with control group (p = 0.042. However, our evaluations indicated that adding topical treatment with 3% gel once a day to the oral therapy with the same product did not make

  14. Transdermal estrogen gel and oral aspirin combination therapy improves fertility prognosis via the promotion of endometrial receptivity in moderate to severe intrauterine adhesion

    Science.gov (United States)

    Chi, Yugang; He, Ping; Lei, Li; Lan, Yi; Hu, Jianguo; Meng, Ying; Hu, Lina

    2018-01-01

    Intrauterine adhesion (IUA) is one of the most common gynecological diseases in women of reproductive age. IUA, particularlyin moderate to severe forms, accounts for a large percentage of infertility cases. Clinically, the first-line treatment strategy for IUA is transcervical resection of adhesion (TCRA), followed by adjuvant postoperative treatment. Estrogen is one of the classic chemotherapies used following TCRA and contributes to preventing re-adhesion following surgery. However, estrogen has limited effects in promoting pregnancy, which is the ultimate goal for IUA management. In the present study, a transdermal estrogen gel and oral aspirin combination therapy was used in patients with IUA following TCRA. Compared with in the control group (transdermal estrogen only therapy), the combination therapy significantly increased endometrial receptivity marker (αvβ٣ and laminin) expression in endometrium tissues. Additionally, ultrasonic examination revealed the pulsatility index and resistant index of the uterine artery were lower in the combination therapy group. Combination therapy promoted angiogenesis and prevented fibrosis following TCRA more effectively than estrogen-only therapy. Collectively, the evaluation indices, including American Fertility Society score, endometrial parameters and pregnancy rate, indicated that patients with combination therapy had better prognoses in endometrial repair and pregnancy. In conclusion, postoperative combination therapy with transdermal estrogen gel and oral aspirin may be more efficacious in enhancing endometrial receptivity by increasing uterine blood and angiogenesis, contributing to improved fertility prognosis. The findings of the present study may provide novel guidance to the clinical treatment of IUA. PMID:29512784

  15. Comparison of diabetes-associated secondary healthcare utilization between alternative oral antihyperglycaemic dual therapy combinations with metformin in patients with type 2 diabetes: an observational cohort study.

    Science.gov (United States)

    Strongman, H; D'Oca, K; Langerman, H; Das, R

    2015-06-01

    To compare diabetes-associated secondary healthcare utilization in patients with type 2 diabetes (T2DM) prescribed sulphonylureas (SUs) versus other oral antihyperglycaemic agents (OHAs) as an add-on to metformin monotherapy (metformin + SU vs metformin + OHA). This retrospective cohort study used data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. Adults with T2DM initiated on metformin + SU or metformin + OHA from April 2003 to March 2012 were identified. Patients were matched using propensity scores. Diabetes-associated secondary healthcare visits were counted from >6 months post-initiation of dual therapy until treatment change or end of follow-up. Outcomes were calculated as rate ratios, adjusted for over-dispersion using negative binomial regression and propensity score for covariates. After propensity score matching, 1704 patients were included in each cohort. For the primary objective (diabetes-associated inpatient and outpatient visits combined), the metformin + SU cohort had a directionally higher rate of diabetes-associated secondary healthcare utilization than the metformin + OHA cohort [adjusted rate ratio 1.12, 95% confidence interval (CI) 0.97-1.29]. For the secondary outcomes, the adjusted rate ratio was 1.38 (95% CI 0.95-2.00) for inpatient admissions and 1.10 (95% CI 0.95-1.28) for outpatient visits. Macrovascular complications, accounting for 77.2% of inpatient admissions, occurred at a statistically significantly higher rate in the metformin + SU cohort than in the metformin + OHA cohort (adjusted rate ratio 1.77, 95% CI 1.15-2.71). This study found a statistically significant higher rate of inpatient admissions for macrovascular complications and cardiology outpatient visits and, overall, a directionally higher rate of secondary healthcare utilization for patients prescribed metformin + SU than for those prescribed metformin + OHA. This adds to the evidence that long

  16. Comparison Of Oral Premedication With Combination Of Midazolam With Ketamine Vs Midazolam Ketamine Alone In Children Children Medical Center (year 2000

    Directory of Open Access Journals (Sweden)

    Hasani M

    2002-09-01

    Full Text Available Anxiolysis and sedation with oral midazolam are common practice in pediatric anesthesia. Good or excellent results are seen in only 50% to 80% of cases, so we decided to investigate if addition of a low dose of oral ketamine to midazolam (ketamine2.5 mg /kg ^midazolam 0.25 mg/kg resulted in better premedication compared with oral midazolam 0.5 mg/kg or ketamine 6 mg/kg alone."nMethods and Materials: in a prospective, randomized ,double -blind study we study 105 children (mean age 6 ,range 2-10 yr. undergoing non thoracic and non cardiac surgery of more than 30 min duration. The patients were in ASA 1, 2. After oral premedication the child's condition was evaluated by assigning 1-4 point to the quality of anxiolysis, sedation, and separation from parents in the induction room .The groups were similar in sex, age, weight, intervention and duration of anaesthesia."nResults: The score of sedation before transfer to the operation room was significantly better in the ketamine, midazolam combination group than in the ketamine or midazolam group. Success rates for anxiolysis and behavior at separation were grater than 90%with the combination, approximately 80% with midazolam and 70% with ketamine alone .The incidence of salivation, excitation, nausea and vomiting was grater in the ketamine group but were very low in other groups. During recovery there were no difference in sedation or time of possible discharge."nConclusion: In summery, significantly better anxiolysis and separation were observed with a combination of ketamine and midazolam, even in awake children than with midazolam or ketamine alone. Duration of action and side effects of the combination was similar to those of midazolam.

  17. Drug-drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucose-lowering agents for the management of type 2 diabetes mellitus.

    Science.gov (United States)

    Scheen, André J

    2014-04-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

  18. Effects of iron oxide contrast agent in combination with various transfection agents during mesenchymal stem cells labelling: An in vitro toxicological evaluation.

    Science.gov (United States)

    Mishra, Sushanta Kumar; Khushu, Subash; Gangenahalli, Gurudutta

    2018-03-22

    The use of iron oxide nanoparticles for different biomedical applications, hold immense promise to develop negative tissue contrast in magnetic resonance imaging (MRI). Previously, we have optimized the labelling of mesenchymal stem cells (MSCs) with iron oxide nanoparticles complexed to different transfection agents like poly-l-lysine (IO-PLL) and protamine sulfate (Fe-Pro) on the basis of relaxation behaviour and its biological expressions. However, there is a distinct need to investigate the biocompatibility and biosafety concerns coupled with its cytotoxicity and genotoxicity. This study was prepared to evaluate the viability of cells, generation of ROS, changes in actin cytoskeleton, investigation of cell death, level of GSH and TAC, activities of SOD and GPx, and stability of DNA in MSCs after labelling. Results demonstrated a marginal alteration in toxicological parameters like ROS generation, cell length, actin cytoskeleton, total apoptosis and DNA damage was detected after stem cell labelling. Insignificant depletion of GSH and SOD level, and increase in GPx and TAC level in MSCs were measured after labelling with IO-PLL and Fe-Pro complexes, which later on recovered and normalized to its baseline. This MSCs labelling could provide a reference guideline for toxicological analysis and relaxometry based in vivo MRI detection. Copyright © 2018. Published by Elsevier Ltd.

  19. Effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2016-11-01

    Full Text Available Objective: To study the effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue. Methods: A total of 144 patients with locally advanced gastric cancer receiving surgical resection after neoadjuvant chemotherapy in our hospital between May 2012 and August 2015 were selected and randomly divided into experimental group who received preoperative oral S-1 combined with regional intra-arterial chemotherapy and control group who received preoperative intravenous systemic chemotherapy. The levels of serum tumor markers were determined after chemotherapy, and the expression levels of tumor suppressor genes and cell cycle-related molecules in tumor tissue were determined after surgical resection. Results: After neoadjuvant chemotherapy, the serum G-17, TK-1, CEA, CA19-9, CA12-5, CA72-4 and CK, CK-MB, ALT, AST levels of experimental group were significantly lower than those of control group; after surgical resection, the p16, p27, PTEN and TXNIP mRNA levels in tumor tissue of experimental group were significantly higher than those of control group while CyclinB2, CyclinD1, CyclinE, CDK1 and CDK2 mRNA levels were significantly lower than those of control group. Conclusions: Preoperative oral S-1 combined with regional intra-arterial chemotherapy can more effectively kill gastric cancer cells, reduce tumor load, inhibit cell cycle and promote cell apoptosis.

  20. Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced oral mucositis and myelosuppression. A controlled study in a rat model

    International Nuclear Information System (INIS)

    Uecuencue, H.; Ertekin, M.V.; Yoeruek, O.; Sezen, O.; Oezkan, A.; Erdogan, F.; Kiziltunc, A.; Guendogdu, C.

    2006-01-01

    The aim of this study was to determine the effects of vitamin E (VE) and L-carnitine (LC) supplementation, separately or in combination, on radiation-induced oral mucositis and myelosuppression. Group 1 received no treatment (control). Group 2 received 15 Gray of 60 Co gamma irradiation as a single dose to total cranium (IR). Group 3, 4, and 5 received irradiation plus 40 mg/kg/day VE (IR+VE) or 200 mg/kg day LC (IR+LC) or in combination (IR+VE+LC) respectively. Clinically and histopathologically, assessments of mucosal reactions were performed by two independent experts in Radiation Oncology and Pathology, respectively. Hematologic analyses and antioxidant enzyme evaluations were also performed. Irradiation significantly increased oral mucositis, and decreased thrombocyte and White Blood Cell counts. A significant increase in malondialdehyde (MDA) levels and decrease in superoxide dismutase (SOD) and catalase (CAT) activities in plasma were found in the IR group. VE and LC administration, separately, plus irradiation significantly delayed the starting day, and reduced the severity of, oral mucositis. This administration also reduced a fall in the numbers of thrombocyte and white blood cell (WBC) caused by irradiation, and decreased the MDA level, and increased the activity of SOD and CAT enzymes in the plasma. VE and LC, in combination, plus irradiation did not provide a superior radioprotection against radiation-induced toxicities. (author)

  1. Triple-combination treatment with oral α-lipoic acid, betamethasone injection, and NB-UVB for non-segmental progressive vitiligo.

    Science.gov (United States)

    Li, Li; Li, Lu; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

    2016-06-01

    Vitiligo is an acquired depigmenting disease with uncertain etiopathogenesis and the treatment modalities need to be consistently updated. To evaluate a triple-combination treatment with oral α-lipoic acid (ALA), betamethasone injection, and narrowband ultraviolet B (NB-UVB) on vitiligo. Patients with non-segmental and progressive vitiligo lesions were randomly assigned to two groups. The treatment group and the control group were respectively treated with oral ALA and placebo, in combination with betamethasone injection and NB-UVB. The effectiveness and adverse events were evaluated by investigators and patients before and after treatment. Fifty non-segmental progressive vitiligo patients were enrolled in the study. The treatment period was 6 months. In treatment group, over 40% patients achieved > 50% improvement and ≥ 5 satisfaction score by 3-month therapy (M3). This percentage increased to 90% at M6. Treatment group achieved better efficacy than control group at M3, while no difference was seen at M6. The combined treatment with oral ALA, betamethasone injection, and NB-UVB was effective and safe on non-segmental progressive vitiligo. ALA could accelerate the initial response of repigmentation.

  2. Oral candidiasis.

    Science.gov (United States)

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

    Science.gov (United States)

    Ward, Mark G; Irving, Peter M; Sparrow, Miles P

    2015-10-28

    In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.

  4. In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.

    Science.gov (United States)

    Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian

    2014-08-01

    The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI conditioning regimens for allo-SCT in advanced-phase CML.

  5. Association of insulin treatment versus oral hypoglycaemic agents with diabetic retinopathy and its severity in type 2 diabetes patients in Cameroon, sub-Saharan Africa.

    Science.gov (United States)

    Jingi, Ahmadou M; Noubiap, Jean Jacques N; Essouma, Mickael; Bigna, Jean Joel R; Nansseu, Jobert Richie N; Ellong, Augustin; Mvogo, Côme Ebana

    2016-10-01

    Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with multiple macro and microvascular complications, diabetic retinopathy (DR) being the commonest one. Recent literature has reported an increased risk of DR with insulin use. We carried out a cross-sectional study at the Ophthalmology Department of the Douala General Hospital (DGH) during a 2-year period to explore the association between insulin treatment and both DR and its severity as compared with oral hypoglycemic agents (OHAs) in Cameroonian T2DM patients aged ≥35 years, and who were all screened for DR through eye examination including exhaustive retinal evaluation. In total, medical files of 134 T2DM patients were analyzed. The frequency of DR was 54.1% among patients on OHA and 73.9% among those on insulin treatment, giving an overall frequency of 57.5%. There were significantly more OHA treated patients than insulin treated patients (82.8% vs . 17.2%, Phistory of hypertension, alcohol misuse, and current tobacco smoking. DR was almost significantly more frequent in T2DM patients under insulin regimen than in patients under OHA [73.9% vs . 54.1%; odds ratio (OR) 2.4; 95% confidence interval (CI), 0.9-6.6; P=0.06]. Proliferative diabetic retinopathy (PDR) was significantly more observed in insulin treated patients than in OHA treated patients (34.8% vs . 15.3%; OR 2.95; 95% CI, 1.1-8; P=0.035). Irrespective of staging, the frequency of diabetic macular edema (DME) was significantly higher in the insulin group than in the OHA group (43.5% vs . 19.8%; OR 3.1; 95% CI, 1.2-8; P=0.019). Compared with OHA, insulin therapy may be associated with DR, DR severity and DME in these T2DM sub-Saharan African patients.

  6. [Control of blood pressure mean and its correlation with renal function in patients with severe preeclampsia treated with three oral antihypertensive agents].

    Science.gov (United States)

    Vázquez Rodríguez, Juan Gustavo

    2009-05-01

    In severe preeclampsia, the lack of blood pressure average is a factor for adverse renal function. To describe the control of blood pressure mean and its correlation with the endogenous creatinine clearance in severe preeclampsia treated with three oral antihypertensive agents cross-sectional study on 123 pregnant women with severe preeclampsia, treated with 500 mg every 8 h methyldopa, hydralazine 50 mg every 6 h, or 100 mg of metoprolol every 12 hours from admission to the unit intensive care to the care delivery. At time of delivery were compared blood pressure average, endogenous creatinine clearance and the correlation between two of the 123 patients were divided into two groups with matching blood pressure treatment goal of 95 mmHg (98 cases, 79.67%). Was used to measures of central tendency and dispersion, T-test and Pearson correlation coefficient (r). Blood pressure mean (mmHg) initial vs final of all patients was similar (114.64 +/- 4.54 vs 103.88 +/- 10.65, p = 1.46) but not the medial blood group A vs B (89.16 +/- 4.54 vs 107.63 +/- 8.22, p = 0.05). Endogenous creatinine clearance (mL/min/1.73 m2 SC) of the total was similar (101.88 +/- 28.48 vs 98.73 +/- 29.96, p = 0.40) in group A increased by 2.5 (p = 0.71) and decreased in group B 5.69 (p = 0.0056). R of the total income to the intensive care unit was 0.11 and the birth of 0.06, 0.0033 in groupA and -0.44 and 0.13 in group B and 0.16, respectively. The satisfactory control of blood pressure was achieved in 20.33% of cases. The correlation between blood pressure mean and endogenous creatinine clearance was very low.

  7. Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

    Science.gov (United States)

    Gu, Shuyan; Wang, Xiaoyong; Qiao, Qing; Gao, Weiguo; Wang, Jian; Dong, Hengjin

    2017-12-01

    To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment. © 2017 John Wiley & Sons Ltd.

  8. Competing intermolecular interactions of artemisinin-type agents and aspirin with membrane phospholipids: Combined model mass spectrometry and quantum-chemical study

    Energy Technology Data Exchange (ETDEWEB)

    Pashynska, Vlada, E-mail: vlada@vl.kharkov.ua [B.Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine, Lenin Ave., 47, 61103 Kharkov (Ukraine); Stepanian, Stepan [B.Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine, Lenin Ave., 47, 61103 Kharkov (Ukraine); Gömöry, Agnes; Vekey, Karoly [Institute of Organic Chemistry of Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Magyar tudosok korutja, 2, Budapest H-1117 (Hungary); Adamowicz, Ludwik [University of Arizona, Department of Chemistry and Biochemistry, Tucson, AZ 85721 (United States)

    2015-07-09

    Highlights: • Competitive binding of artemisinin agents and aspirin with phospholipids is shown. • Complexation between the antimalarial drugs and aspirin molecules is also found. • Energetically favorable structures of the model complexes are identified by DFT. • Membranotropic activity of the studied drugs can be modified under joint usage. - Abstract: Study of intermolecular interactions of antimalarial artemisinin-type drugs and aspirin with membrane phospholipids is important in term of elucidation of the drugs activity modification under their joint usage. Combined experimental and computational study of the interaction of dihydroartemisinin, α-artemether, and artesunate with aspirin (ASP) and dipalmitoylphosphatidylcholine (DPPC) is performed by electrospray ionization (ESI) mass spectrometry and by DFT B3LYP/aug-cc-pVDZ methods. The results of the ESI investigation of systems containing artemisinin-type agent, ASP and DPPC, reveal a competition between the antimalarial agents and ASP for binding with DPPC molecules. The complexation between the antimalarial drugs and ASP is also found. Observed phenomena suggest that membranotropic activity of artemisin-type agents and aspirin is modified under their combined usage. To elucidate structure-energy characteristics of the non-covalent complexes studied the model DFT calculations are performed for dihydroartemisinin · ASP complex and complexes of the each drug with phosphatidylcholine head of DPPC in neutral and cationized forms.

  9. Competing intermolecular interactions of artemisinin-type agents and aspirin with membrane phospholipids: Combined model mass spectrometry and quantum-chemical study

    International Nuclear Information System (INIS)

    Pashynska, Vlada; Stepanian, Stepan; Gömöry, Agnes; Vekey, Karoly; Adamowicz, Ludwik

    2015-01-01

    Highlights: • Competitive binding of artemisinin agents and aspirin with phospholipids is shown. • Complexation between the antimalarial drugs and aspirin molecules is also found. • Energetically favorable structures of the model complexes are identified by DFT. • Membranotropic activity of the studied drugs can be modified under joint usage. - Abstract: Study of intermolecular interactions of antimalarial artemisinin-type drugs and aspirin with membrane phospholipids is important in term of elucidation of the drugs activity modification under their joint usage. Combined experimental and computational study of the interaction of dihydroartemisinin, α-artemether, and artesunate with aspirin (ASP) and dipalmitoylphosphatidylcholine (DPPC) is performed by electrospray ionization (ESI) mass spectrometry and by DFT B3LYP/aug-cc-pVDZ methods. The results of the ESI investigation of systems containing artemisinin-type agent, ASP and DPPC, reveal a competition between the antimalarial agents and ASP for binding with DPPC molecules. The complexation between the antimalarial drugs and ASP is also found. Observed phenomena suggest that membranotropic activity of artemisin-type agents and aspirin is modified under their combined usage. To elucidate structure-energy characteristics of the non-covalent complexes studied the model DFT calculations are performed for dihydroartemisinin · ASP complex and complexes of the each drug with phosphatidylcholine head of DPPC in neutral and cationized forms

  10. Novel Agent Based-approach for Industrial Diagnosis: A Combined use Between Case-based Reasoning and Similarity Measure

    Directory of Open Access Journals (Sweden)

    Fatima Zohra Benkaddour

    2016-12-01

    Full Text Available In spunlace nonwovens industry, the maintenance task is very complex, it requires experts and operators collaboration. In this paper, we propose a new approach integrating an agent- based modelling with case-based reasoning that utilizes similarity measures and preferences module. The main purpose of our study is to compare and evaluate the most suitable similarity measure for our case. Furthermore, operators that are usually geographically dispersed, have to collaborate and negotiate to achieve mutual agreements, especially when their proposals (diagnosis lead to a conflicting situation. The experimentation shows that the suggested agent-based approach is very interesting and efficient for operators and experts who collaborate in INOTIS enterprise.

  11. Preparation, characterization and in vitro release kinetics of polyaspartamide-based conjugates containing antimalarial and anticancer agents for combination therapy

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2016-09-01

    Full Text Available Malaria is treated by combination of two drugs in order to overcome drug resistance. Antimalarials have been found to be more effective by combining them with low doses of anticancer drugs. Polymer-drug conjugates containing aminoquinoline...

  12. Comparison between oral and intra-articular antinociceptive effect of dexketoprofen and tramadol combination in monosodium iodoacetate-induced osteoarthritis in rats.

    Science.gov (United States)

    Cialdai, Cecilia; Giuliani, Sandro; Valenti, Claudio; Tramontana, Manuela; Maggi, Carlo Alberto

    2013-08-15

    Dexketoprofen and tramadol, alone or in combination, were evaluated after oral or intra-articular administration on knee osteoarthritis nociception induced by intra-articular (i.ar.) monosodium iodoacetate (MIA, 1 mg/25 µl) in the rat right knee while the left knee received saline (25 µl). Seven days after MIA treatment, dexketoprofen, tramadol, their combination or the vehicle were administered. Nociception was evaluated as alteration in hind limb weight distribution with Incapacitance tester at different time-points after drug administration. Oral dexketoprofen (0.1-1 mg/kg) or tramadol (0.5-5 mg/kg) induced maximal antinociception at 1 and 5 mg/kg, respectively. Their combination dose-dependently increased the intensity and duration of antinociception, that was additive and lasted up to 3 days. Also the intra-articular administration of dexketoprofen or tramadol (10-100 µg/25 µl) inhibited MIA-induced nociception, and the combination of the lower doses (10 µg/25 µl) produced a long lasting more than additive antinociceptive effect indicating a synergistic interaction between the two drugs. This effect was significantly reduced by naloxone (10 μg/25 μl, i.ar.) co-administered with both compounds. The intra-articular administration of both drugs at 10 µg/25 µl in the contralateral control knee joint provoked a marked synergistic antinociceptive effect indicating significant systemic diffusion through synovial membrane. The oral or intra-articular combination of dexketoprofen and tramadol produced additive or synergistic antinociceptive effects, respectively, in the model of MIA-induced osteoarthritis in rats, that might allow to obtain therapeutic advantages with lower side effects. © 2013 Elsevier B.V. All rights reserved.

  13. Testing Social-driven Forces on the Evolution of Sahelian Rural Systems: A Combined Agent-based Modeling and Anthropological Approach

    OpenAIRE

    Saqalli , Mehdi; Gérard , B.; Bielders , C.; Defourny , Pierre

    2010-01-01

    International audience; This article presents the results of a methodology combining an extensive fieldwork, a formalization of field-based individual rules and norms into an agent-based model and the implementation of scenarios analyzing the effects of social and agro-ecological constraints on rural farmers through the study of three different sites in Nigerien Sahel. Two family transition processes are here tested, following field observations and literature-based hypotheses: family organiz...

  14. Dipeptidyl Peptidase-4 Inhibitors as a Third-Line Oral Antihyperglycaemic Agent in Patients with Type 2 Diabetes Mellitus: The Impact of Ethnicity

    Directory of Open Access Journals (Sweden)

    X. Zhang

    2014-01-01

    Full Text Available Aims. The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4 inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment. The response of Asian and non-Asian patients to this regimen was also examined. Methods. The medical and computerized records of 80 patients were examined. These patients had baseline HbA1c levels ranging from 7.0 to 12.5% and had a DPP-4 inhibitor add-on therapy for a minimum period of 12 weeks. The primary endpoint was the change in HbA1c level before and after DPP-4 inhibitor treatment. Results. During oral triple therapy, there was a reduction of HbA1c from 8.3% (7.7–8.9 to 7.2% (6.8–7.6 and 26 patients (32.5% achieved an HbA1c <7%. Poor baseline glycaemic control, lower BMI, and younger age were associated with a better response, but duration of diabetes and gender did not affect outcome. The HbA1c reduction was not different between Asians and non-Asians group [−1.00% (0.6–1.3 vs −0.90% (0.4–1.6]. Conclusions. DPP-4 inhibitor as a third-line add-on therapy can achieve significant glycaemic improvement in patients with type 2 diabetes inadequately controlled on the combination of metformin and sulphonylurea. The improvement in HbA1c was similar between Asian and non-Asian patients.

  15. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: A real-life worldwide observational study (EDGE)

    Science.gov (United States)

    Mathieu, C; Barnett, A H; Brath, H; Conget, I; de Castro, J J; Göke, R; Márquez Rodriguez, E; Nilsson, P M; Pagkalos, E; Penfornis, A; Schaper, NC; Wangnoo, S K; Kothny, W; Bader, G

    2013-01-01

    Aim Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale ‘pragmatic’ trials. Methods EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA1c > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA1c vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p vildagliptin and other OADs were consistent with previous data. Conclusion EDGE demonstrates that in a ‘real-life’ setting, vildagliptin as second OAD can lower HbA1c to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs. PMID:23961850

  16. Combination Effect of Hemostatic and Disinfecting Agents on Micro-leakage of Restorations Bonded with Different Bonding Systems

    Directory of Open Access Journals (Sweden)

    Farhadpour H

    2016-09-01

    Full Text Available Statement of Problem: Hemostatic agents may affect the micro-leakage of different adhesive systems. Also, chlorhexidine has shown positive effects on micro-leakage. However, their interaction effect has not been reported yet. Objectives: To evaluate the effect of contamination with a hemostatic agent on micro- leakage of total- and self-etching adhesive systems and the effect of chlorhexidine application after the removal of the hemostatic agent. Materials and Methods: Standardized Class V cavity was prepared on each of the sixty caries free premolars at the cemento-enamel junction, with the occlusal margin located in enamel and the gingival margin in dentin. Then, the specimens were randomly divided into 6 groups (n = 10 according to hemostatic agent (H contamination, chlorhexidine (CHX application, and the type of adhesive systems (Adper Single Bond and Clearfil SE Bond used. After filling the cavities with resin composite, the root apices were sealed with utility wax. Furthermore, all the surfaces, except for the restorations and 1mm from the margins, were covered with two layers of nail varnish. The teeth were immersed in a 0.5% basic fuschin dye for 24 hours, rinsed, blot-dried and sectioned longitudinally through the center of the restorations bucco- lingualy. The sections were examined using a stereomicroscope and the extension of dye penetration was analyzed according to a non-parametric scale from 0 to 3. Statistical analysis was performed using Kruskal-Wallis test and Mann-Whitney U-test. Results: While ASB group showed no micro-leakage in enamel, none of the groups showed complete elimination of micro-leakage from the dentin. Regarding micro- leakage at enamel, and dentin margins, there was no significant difference between groups 1 and 2, 1 and 3, and 2 and 3 (p > 0.05. A significantly lower micro-leakage at the enamel and dentin margins was observed in group 3, compared to group 6. No significant difference was observed between

  17. Impact of a sodium carbonate spray combined with professional oral hygiene procedures in patients with Sjögren's syndrome: an explorative study.

    Science.gov (United States)

    Gambino, Alessio; Broccoletti, Roberto; Cafaro, Adriana; Cabras, Marco; Carcieri, Paola; Arduino, Paolo G

    2017-06-01

    The aim of this study was to make an initial estimation on the effects of a sodium bicarbonate and xylitol spray (Cariex ® ), associated with non-surgical periodontal therapy, in participants with primary Sjögren's syndrome. Sjögren's syndrome (SS) is a multisystem autoimmune disease that predominantly involves salivary and lachrymal glands, with the clinical effect of dry eyes and mouth. A prospective cohort of 22 women and two men has been evaluated. They were randomized into three groups (eight patients each): Group A) those treated once with non-surgical periodontal therapy, education and motivation to oral hygiene, associated with the use of Cariex ® ; Group B) treated only with Cariex ® ; Group C) treated only with non-surgical periodontal therapy, education and motivation to oral hygiene. Clinical variables described after treatment were unstimulated whole salivary flow, stimulated whole salivary flow, salivary pH, reported pain (using Visual Analogue Scale) and the Periodontal Screening and Recording index. Salivary flow rate improved in all groups, but the difference was statistically significant only in those treated with Cariex ® , alone or in combination with periodontal therapy. Gingival status improved in participants who underwent periodontal non-surgical therapy while remained unchanged in those only treated with Cariex ® . Reported pain decreased in all groups, showing the best result in participants treated with periodontal therapy together with Cariex ® . We propose a practical approach for improving gingival conditions and alleviating oral symptoms in patients with SS. Future randomized and controlled trials are however required to confirm these results as well as larger population, and also assessing other parameters due to oral dryness, possible oral infections and more comprehensive periodontal indices. © 2016 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

  18. The early diagnostic value of oral acetazolamide load combined with SPECT rCBF imaging in patients with transient ischemia attack in brain

    International Nuclear Information System (INIS)

    Liu Xintong; Zheng Zhiping; Qiao Suixian; Tang Anwu

    2001-01-01

    Objective: In order to assess the diagnostic value of acetazolamide (ACZ) combined with rCBF-SPECT imaging in patients with transient ischemia attack (TIA). Methods: SPECT imaging was performed before and after oral ACZ with visual and semiquantitative analysis of the images. Blood gas analysis was done before and after ACZ administration either. Results: After ACZ loading, in normal group, 99 Tc m -ECD was distributed symmetrically on correspondent parts of the brain and rCBF was generally increased. The blood pH was decreased and blood PCO 2 was increased, respectively in TIA group, the positive rate of hypoperfusion foci on SPECT images were increased from 5/6 to 6/6 in symptomatic patients and from 60% to 92% in asymptomatic patients. The total positive rate was 93%. Conclusion: Oral ACZ before SPECT imaging is a simple, reliable way for early diagnosis in patients with TIA

  19. CT, MR, 18F-FDG PET/CT, and their combined use for the assessment of mandibular invasion by squamous cell carcinomas of the oral cavity

    International Nuclear Information System (INIS)

    Gu, Dong Hyeon; Yoon, Dae Young; Chang, Suk Ki; Lim, Kyoung Ja; Seo, Young Lan; Yun, Eun Joo; Choi, Chul Soon; Bae, Sang Hoon; Park, Hee Chan

    2010-01-01

    Background: A reliable assessment of mandibular invasion is crucial for treatment planning to obtain both radical tumor resection and good functional results. Purpose: To retrospectively compare the diagnostic value of three different imaging methods - computed tomography (CT), magnetic resonance (MR) imaging, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT - and their combined use for detection of mandibular invasion by squamous cell carcinoma (SCC) of the oral cavity. Material and Methods: Forty-six patients (39 men and 7 women; mean age, 59.4 years) suspected of having mandibular invasion by SCC of the oral cavity underwent CT, MR, and PET/CT within 2 weeks before surgery. First, each study was reviewed separately for the presence of mandibular invasion by tumors. Then, the value of combined images was assessed based on a confidence rating score for each modality assigned by observers. These results were verified with histopathologic findings. Results: Histopathologic examination revealed mandibular invasion in 12 of 46 SCCs. The sensitivity, specificity, and accuracy were 41.7%, 100%, and 84.8% for CT; 58.3%, 97.1%, and 87.0% for MR; and 58.3%, 97.1%, and 87.0% for PET/CT, respectively. The comparison of these modalities showed no statistically significant difference among them (P > 0.05). The combination of CT, MR, and PET/CT improved sensitivity (83.3%), without loss of specificity (100%) and accuracy (95.7%), although the difference failed to reach statistical significance (P > 0.05). Conclusion: The combined analysis of CT, MR, and PET/CT can improve sensitivity in the detection of mandibular invasion by SCC of the oral cavity

  20. Combined effects of biocontrol agents and soil amendments on soil microbial populations, plant growth and incidence of charcoal rot of cowpea and wilt of cumin

    Directory of Open Access Journals (Sweden)

    Vijeta SINGH

    2012-09-01

    Full Text Available Field experiments were conducted for 2 years to determine the effectiveness of combined use of two biocontrol agents, Bacillus firmus and Aspergillus versicolor for control of Macrophomina phaseolina induced charcoal rot of cowpea and Fusarium oxysporum f. sp. cumini induced wilt of cumin. The lowest level of plant mortality (3‒4% due to charcoal rot of cowpea was recorded when bacterium coated seeds were sown in radish compost amended soil compared to the non-amended soil (13.8‒20.5%, but this was not significantly better than some other treatments. Cowpea roots from B. firmus coated seeds had better nodulation than any of the individual A. versicolor treatments. Although B. firmus coated seeds + A. versicolor + farmyard manure resulted in maximum nodulation this was not significantly different to B. firmus seed coating. Root colonization by the combined biocontrol agent treatments was better than the individual biocontrol agent treatments. Combining A. versicolor with farmyard manure supported the maximum populations of total fungi and actinomycetes. In both winter seasons, the lowest incidence of wilt (1.0‒5.2% on cumin was recorded when A. versicolor was amended with neem compost compared to the non-amended soil (5.7‒10.5%. Maximum colonization of A. versicolor on roots was observed in B. firmus + A. versicolor + farmyard manure amended plots. During both years, the treatment combination of A. versicolor in neem compost amended plots resulted in maximum populations of fungi, bacteria and A. versicolor in the soil, which was greater than in the non-amended soil. Significant increases in disease control were not recorded after single or repeated delivery of A. versicolor. These results suggest that combining B. firmus as seed coatings with A. versicolor as soil applications gives improved control of M. phaseolina and Fusarium induced diseases on legume and seed spice crops in arid soils.

  1. Dexmedetomidine, ketamine, and midazolam for oral rehabilitation: a case report.

    Science.gov (United States)

    Kim, Bill W S; Peskin, Robert M

    2015-01-01

    Intravenous sedation is frequently provided by anesthesiologists for phobic patients undergoing elective dental treatment in outpatient settings. Propofol is one of the most commonly used anesthetic agents that can result in apnea and respiratory depression, thereby posing potential difficulties with perioperative airway management. Dexmedetomidine has been utilized successfully in intravenous sedation for a wide variety of procedures and holds potential as an alternative to propofol in outpatient dental settings. However, as a single agent, it may not provide adequate depth of sedation and analgesia for oral rehabilitation. In this case report we demonstrate an effective alternative intravenous deep-sedation technique for an adult phobic patient undergoing oral rehabilitation utilizing 3 agents in combination: dexmedetomidine, ketamine, and midazolam. This combination of agents may be especially useful for those patients with a history of substance abuse, where administration of opioids may be undesirable or contraindicated.

  2. Metronidazole combined with nystatin (vagitories) in the prevention of bacterial vaginosis after initial treatment with oral metronidazole.

    Science.gov (United States)

    Pulkkinen, P; Saranen, M; Kaaja, R

    1993-01-01

    In a double-blind trial comprising 66 patients we assessed the effect of metronidazole-nystatin vagitories on the prevention of bacterial vaginosis (BV) in women using IUD as a contraceptive method after an initial oral single dose of 2.0 g metronidazole and 7 days of intravaginal metronidazole-nystatin or placebo treatment. The prophylactic treatment consisted of metronidazole-nystatin or placebo vagitories applied at bedtime for 3 days after menstruation over 6 consecutive menstrual periods. The patients were randomized in two study groups: a treatment group of 32 patients (group A) and a placebo group of 34 patients (group B). The overall objective cure rate after the initial treatment was 97% in group A and 91% in group B. After 6 months of follow-up, the overall cumulative objective cure rate in group A was 100%, and 76% in group B. The single-dose oral treatment was well tolerated and no notable side effects were recorded.

  3. An outpatient regimen of combined oral mifepristone 400 mg and misoprostol 400 microg for first-trimester legal medical abortion

    DEFF Research Database (Denmark)

    Ravn, Pernille; Rasmussen, Ase; Knudsen, Ulla Breth

    2005-01-01

    AIM: To evaluate the success rate of medical abortion using an outpatient regimen of oral mifepristone 400 mg and oral misoprostol 400 microg for legal abortion in women abortion was defined as an endometrial thickness ... the procedure over a 3-year period and 606 (92%) experienced successful medical abortion. The remaining 8% had vacuum aspiration performed mainly due to uterine retention (70%). Other reasons were vaginal bleeding (25%), vomiting (2%), or pelvic infection (4%). Most women reported no days with severe pain (67......%), 0--1 days with moderate pain (82%), and 0--1 days with light pain (62%). In terms of gastrointestinal side effects, 68% reported nausea, 33% vomiting, and 27% diarrhea. Most women (90%) felt that the information given at the hospital prior to the abortion was sufficient, 74% would prefer medical...

  4. Enhanced bioavailability of orally administered flurbiprofen by combined use of hydroxypropyl-cyclodextrin and poly(alkyl-cyanoacrylate) nanoparticles.

    Science.gov (United States)

    Zhao, Xiaoyun; Li, Wei; Luo, Qiuhua; Zhang, Xiangrong

    2014-03-01

    Flurbiprofen was formulated into nanoparticle suspension to improve its oral bioavailability. Hydroxypropyl-β-cyclodextrin inclusion-flurbiprofen complex (HP-β-CD-FP) was prepared, then incorporating this complex into poly(alkyl-cyanoacrylate) (PACA) nanoparticles. HP-β-CD-FP-PACA nanoparticle was prepared by the emulsion solvent polymerization method. The zeta potential was -26.8 mV, the mean volume particle diameter was 134 nm, drug encapsulation efficiency was 53.3 ± 3.6 % and concentration was 1.5 mg/mL. The bioavailability of flurbiprofen from optimized nanoparticles was assessed in male Wistar rats at a dose of 15 mg/kg. As compared to the flurbiprofen suspension, 211.6 % relative bioavailability was observed for flurbiprofen nanoparticles. The reduced particle size and increased surface area may contribute to improve oral bioavailability of flurbiprofen.

  5. Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill--a double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive.

    Science.gov (United States)

    Gingnell, Malin; Engman, Jonas; Frick, Andreas; Moby, Lena; Wikström, Johan; Fredrikson, Mats; Sundström-Poromaa, Inger

    2013-07-01

    Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing. Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale. During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala. COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Safety test of a supplement, 5-aminolevulinic acid phosphate with sodium ferrous citrate, in diabetic patients treated with oral hypoglycemic agents

    Directory of Open Access Journals (Sweden)

    Naohide Yamashita

    2014-09-01

    Full Text Available Objective: This study aimed to examine the safety of 5-aminolevulinic acid phosphate (5-ALA with sodium ferrous citrate (SFC in diabetic patients treated with one or more oral hypoglycemic agents (OHAs. Background: Recent intervention studies performed in the USA and Japan have shown that a nutritional supplement of 5-ALA with SFC efficiently reduced blood glucose levels in pre-diabetic population without any adverse events. Thus, it was anticipated that 5-ALA with SFC may potentially be taken as a beneficial supplement by diabetic patients who were being treated with OHA therapy. Nevertheless, it is important to examine its safety and efficacy in diabetic population. Methods: This study was a prospective single-blinded, randomized, placebo-controlled and parallel-group comparison study. Medically treated diabetic patients between the ages of 30 and 75 were recruited from the Tokyo metropolitan area of Japan and 45 subjects were selected after screening. These subjects were randomly assigned to three groups: daily intake of 15mg 5-ALA, 50mg 5-ALA, and a placebo (n=15, respectively. The supplement or placebo was administered for 12 weeks followed by a four week washout period. The primary endpoint was safety and occurrence of hypoglycemic attack, while the secondary endpoint was changes of fasting blood glucose (FBG and hemoglobin A1c (HbA1c. Results: Adverse events related to 5-ALA with SFC were not observed in all the groups. Abnormalities in blood and urine tests were not observed either. Significant decrease in FBG was not detected in all the groups. However, there was a small but significant decrease in HbA1c at 4 and 8 week in the 15 mg 5-ALA group. Significant decrease in HbA1c was not observed in the 50 mg 5-ALA group, although a tendency to decrease after 4 weeks was apparent. Conclusion: 5-ALA with SFC is a safe and potentially beneficial supplement if taken by diabetic patients treated with OHAs.

  7. In vitro and in vivo anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Luo, Qingqiong; Hu, Dan; Hu, Shuiqing; Yan, Ming; Sun, Zujun; Chen, Fuxiang

    2012-01-01

    Metformin, which is widely used as an antidiabetic agent, has recently been reported to reduce cancer risk and improve prognosis in certain malignancies. However, the specific mechanisms underlying the effect of metformin on the development and progression of several cancers including oral squamous cell carcinoma (OSCC) remain unclear. In the present study, we investigated the effects of metformin on OSCC cells in vitro and in vivo. OSCC cells treated with or without metformin were counted using a hemocytometer. The clonogenic ability of OSCC cells after metformin treatment was determined by colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the activation of related signaling pathways was examined by immunoblotting. The in vivo anti-tumor effect of metformin was examined using a xenograft mouse model. Immunohistochemistry and TUNEL staining were used to determine the expression of cyclin D1 and the presence of apoptotic cells in tumors from mice treated with or without metformin. Metformin inhibited proliferation in the OSCC cell lines CAL27, WSU-HN6 and SCC25 in a time- and dose-dependent manner, and significantly reduced the colony formation of OSCC cells in vitro. Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase. Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells. In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax. Metformin also markedly reduced the expression of cyclin D1 and increased the numbers of apoptotic cells in vivo, thus inhibiting

  8. Cytotoxic effects of the newly-developed chemotherapeutic agents 17-AAG in combination with oxaliplatin and capecitabine in colorectal cancer cell lines.

    Science.gov (United States)

    Mohammadian, Mahshid; Zeynali, Shima; Azarbaijani, Anahita Fathi; Khadem Ansari, Mohammad Hassan; Kheradmand, Fatemeh

    2017-12-01

    The use of heat shock protein 90 inhibitors like 17-allylamino-17-demethoxy-geldanamycin (17-AAG) has been recently introduced as an attractive anticancer therapy. It has been shown that 17-AAG may potentiate the inhibitory effects of some classical anticolorectal cancer (CRC) agents. In this study, two panels of colorectal carcinoma cell lines were used to evaluate the effects of 17-AAG in combination with capecitabine and oxaliplatin as double and triple combination therapies on the proliferation of CRC cell lines. HT-29 and all HCT-116 cell lines were seeded in culture media in the presence of different doses of the mentioned drugs in single, double, and triple combinations. Water-soluble tetrazolium-1 (WST-1) assay was used to investigate cell proliferation 24 h after treatments. Then, dose-response curves were plotted using WST-1outputs, and IC 50 values were determined. For double and triple combinations respectively 0.5 × IC 50 and 0.25 × IC 50 were used. Data was analyzed with the software CompuSyn. Drug interactions were analyzed using Chou-Talalay method to calculate the combination index (CI).The data revealed that 17-AAG shows a potent synergistic interaction (CI 1) in HT-29 and a synergistic effect (CI AAG with oxaliplatin or capecitabine might be effective against HCT-116 and HT-29 cell lines. However, in triple combinations, positive results were seen only against HCT-116. Further investigation is suggested to confirm the effectiveness of these combinations in clinical trials.

  9. Antifungal activities of diphenyl diselenide and ebselen alone and in combination with antifungal agents against Fusarium spp.

    Science.gov (United States)

    Venturini, Tarcieli Pozzebon; Chassot, Francieli; Loreto, Érico Silva; Keller, Jéssica Tairine; Azevedo, Maria Izabel; Zeni, Gilson; Santurio, Janio Morais; Alves, Sydney Hartz

    2016-07-01

    Herein, we describe the in vitro activity of a combination of the organoselenium compounds diphenyl diselenide and ebselen alone and in combination with amphotericin B, caspofungin, itraconazole, and voriconazole against 25 clinical isolates of Fusarium spp. For this analysis, we used the broth microdilution method based on the M38-A2 technique and checkerboard microdilution method. Diphenyl diselenide (MIC range = 4-32 μg/ml) and ebselen (MIC range = 2-8 μg/ml) showed in vitro activity against the isolates tested. The most effective combinations were (synergism rates): ebselen + amphotericin B (88%), ebselen + voriconazole (80%), diphenyl diselenide + amphotericin B (72%), and diphenyl diselenide + voriconazole (64%). Combination with caspofungin resulted in low rates of synergism: ebselen + caspofungin, 36%, and diphenyl diselenide + caspofungin, 28%; combination with itraconazole demonstrated indifferent interactions. Antagonistic effects were not observed for any of the combinations tested. Our findings suggest that the antifungal potential of diphenyl diselenide and ebselen deserves further investigation in in vivo experimental models, especially in combination with amphotericin B and voriconazole. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. An agent-based simulation combined with group decision-making technique for improving the performance of an emergency department

    Directory of Open Access Journals (Sweden)

    M. Yousefi

    Full Text Available This study presents an agent-based simulation modeling in an emergency department. In a traditional approach, a supervisor (or a manager allocates the resources (receptionist, nurses, doctors, etc. to different sections based on personal experience or by using decision-support tools. In this study, each staff agent took part in the process of allocating resources based on their observation in their respective sections, which gave the system the advantage of utilizing all the available human resources during the workday by being allocated to a different section. In this simulation, unlike previous studies, all staff agents took part in the decision-making process to re-allocate the resources in the emergency department. The simulation modeled the behavior of patients, receptionists, triage nurses, emergency room nurses and doctors. Patients were able to decide whether to stay in the system or leave the department at any stage of treatment. In order to evaluate the performance of this approach, 6 different scenarios were introduced. In each scenario, various key performance indicators were investigated before and after applying the group decision-making. The outputs of each simulation were number of deaths, number of patients who leave the emergency department without being attended, length of stay, waiting time and total number of discharged patients from the emergency department. Applying the self-organizing approach in the simulation showed an average of 12.7 and 14.4% decrease in total waiting time and number of patients who left without being seen, respectively. The results showed an average increase of 11.5% in total number of discharged patients from emergency department.

  11. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials

    Directory of Open Access Journals (Sweden)

    Xu L

    2016-07-01

    Full Text Available Liang Xu,1,2,* Xiaobo Wu,3,* Chun Hu,1,2 Zhiying Zhang,4 Le Zhang,1,2 Shujing Liang,1,2 Yingchun Xu,5 Fengchun Zhang1,2 1Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, 2Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 3Prevention and Cure Center of Breast Disease, Third Hospital of Nanchang, Nanchang, 4Graduate School, Xuzhou Medical College, Xuzhou, 5Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Nowadays, the philosophy of treating metastatic breast cancer (MBC is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015 comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS, and the secondary end points were the progression-free survival (PFS, overall response rate (ORR, and grade 3 or 4 toxicities. The pooled hazard ratio (HR and pooled risk ratio (RR were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84–0.96, P=0.002, PFS (HR 0.81, 95% CI 0.76–0.88, P<0.001, and ORR (RR 1.72, 95% CI 1.34–2.21, P<0.001. Notably, subgroup analysis

  12. Comparison between Combination Therapy of Oral Terbinafine and Cryotherapy versus Systemic Meglumine Antimoniate and Cryotherapy in Cutaneous Leishmaniasis: A Randomized Clinical Trial.

    Science.gov (United States)

    Farajzadeh, Saeedeh; Esfandiarpour, Iraj; Haghdoost, Ali Akbar; Mohammadi, Saman; Mohebbi, Azadeh; Mohebbi, Elham; Mostafavi, Mahshid

    2015-01-01

    Leishmaniasis is a parasitic infection that may lead to a variety of manifestations. In Iran, cutaneous leishmaniasis (CL) has a high prevalence. There are many treatment modalities for CL. The use of oral terbinafine in the treatment of CL has recently been considered. The aim of this study was to compare combination of oral terbinafine plus cryotherapy versus systemic meglumine antimoniate plus cryotherapy in CL. Patients with proven direct smear for CL were divided randomly in 2 groups of 40 cases. For the first group systemic glucantime prescribed (IM, 15 mg/kg/day) for 3 weeks. For the second group oral terbinafine as two folds of usual dose in the treatment of fungal diseases prescribed [125 mg/day for body weight (BW) 40 kg] for 4 weeks. Both groups received cryotherapy every 2 weeks for 4 weeks. The patients were followed monthly for 3 months after the treatment. Partial (HR= 0.55, CI 95%= 0.3-1.1) and complete (HR= 0.53, CI 95%= 0.3-0.98) clinical improvement in terbinafine group was much slower than glucantime group, although at the end of treatment protocols no significant difference between groups were statistically observed (P=0.27). Considering more convenient suitable route of administration and approximately comparable results, it seems that terbinafine can be used as an alternative treatment, especially in the case of allergy or resistance to systemic glucantime.

  13. Whitening Agents from Reseda luteola L. and Their Chemical Characterization Using Combination of CPC, UPLC-HRMS and NMR

    Directory of Open Access Journals (Sweden)

    Pauline Burger

    2017-11-01

    Full Text Available Skin whitening agents occupy an important part of the dermo-cosmetic market nowadays. They are used to treat various skin pigmentation disorders, or simply to obtain a lighter skin tone. The use of traditional skin bleachers (e.g., hydroquinone, corticoids is now strictly regulated due to their side effects. When considering this and the growing consumers’ interest for more natural ingredients, plant extracts can be seen as safe and natural alternatives. In this perspective, in vitro bioassays were undertaken to assess cosmetic potential of Reseda luteola, and particularly its promising whitening activities. A bioguided purification procedure employing centrifugal partition chromatography, Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-HRMS and NMR was developed to isolate and identify the whitening agents (i.e., luteolin and apigenin from aerial parts of R. luteola. UPLC-HRMS also enabled the characterization of acetylated luteolin- and apigenin-O-glycosides, which occurrence is reported for the first time in R. luteola.

  14. Combining a Multi-Agent System and Communication Middleware for Smart Home Control: A Universal Control Platform Architecture

    Science.gov (United States)

    Zheng, Song; Zhang, Qi; Zheng, Rong; Huang, Bi-Qin; Song, Yi-Lin; Chen, Xin-Chu

    2017-01-01

    In recent years, the smart home field has gained wide attention for its broad application prospects. However, families using smart home systems must usually adopt various heterogeneous smart devices, including sensors and devices, which makes it more difficult to manage and control their home system. How to design a unified control platform to deal with the collaborative control problem of heterogeneous smart devices is one of the greatest challenges in the current smart home field. The main contribution of this paper is to propose a universal smart home control platform architecture (IAPhome) based on a multi-agent system and communication middleware, which shows significant adaptability and advantages in many aspects, including heterogeneous devices connectivity, collaborative control, human-computer interaction and user self-management. The communication middleware is an important foundation to design and implement this architecture which makes it possible to integrate heterogeneous smart devices in a flexible way. A concrete method of applying the multi-agent software technique to solve the integrated control problem of the smart home system is also presented. The proposed platform architecture has been tested in a real smart home environment, and the results indicate that the effectiveness of our approach for solving the collaborative control problem of different smart devices. PMID:28926957

  15. Combining a Multi-Agent System and Communication Middleware for Smart Home Control: A Universal Control Platform Architecture.

    Science.gov (United States)

    Zheng, Song; Zhang, Qi; Zheng, Rong; Huang, Bi-Qin; Song, Yi-Lin; Chen, Xin-Chu

    2017-09-16

    In recent years, the smart home field has gained wide attention for its broad application prospects. However, families using smart home systems must usually adopt various heterogeneous smart devices, including sensors and devices, which makes it more difficult to manage and control their home system. How to design a unified control platform to deal with the collaborative control problem of heterogeneous smart devices is one of the greatest challenges in the current smart home field. The main contribution of this paper is to propose a universal smart home control platform architecture (IAPhome) based on a multi-agent system and communication middleware, which shows significant adaptability and advantages in many aspects, including heterogeneous devices connectivity, collaborative control, human-computer interaction and user self-management. The communication middleware is an important foundation to design and implement this architecture which makes it possible to integrate heterogeneous smart devices in a flexible way. A concrete method of applying the multi-agent software technique to solve the integrated control problem of the smart home system is also presented. The proposed platform architecture has been tested in a real smart home environment, and the results indicate that the effectiveness of our approach for solving the collaborative control problem of different smart devices.

  16. Combining a Multi-Agent System and Communication Middleware for Smart Home Control: A Universal Control Platform Architecture

    Directory of Open Access Journals (Sweden)

    Song Zheng

    2017-09-01

    Full Text Available In recent years, the smart home field has gained wide attention for its broad application prospects. However, families using smart home systems must usually adopt various heterogeneous smart devices, including sensors and devices, which makes it more difficult to manage and control their home system. How to design a unified control platform to deal with the collaborative control problem of heterogeneous smart devices is one of the greatest challenges in the current smart home field. The main contribution of this paper is to propose a universal smart home control platform architecture (IAPhome based on a multi-agent system and communication middleware, which shows significant adaptability and advantages in many aspects, including heterogeneous devices connectivity, collaborative control, human-computer interaction and user self-management. The communication middleware is an important foundation to design and implement this architecture which makes it possible to integrate heterogeneous smart devices in a flexible way. A concrete method of applying the multi-agent software technique to solve the integrated control problem of the smart home system is also presented. The proposed platform architecture has been tested in a real smart home environment, and the results indicate that the effectiveness of our approach for solving the collaborative control problem of different smart devices.

  17. Boron biodistribution for BNCT in the hamster cheek pouch oral cancer model: Combined administration of BSH and BPA

    Energy Technology Data Exchange (ETDEWEB)

    D.W. Nigg; William Bauer; Various Others

    2014-06-01

    Sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically for BNCT. We examined the biodistribution of BSH and BPA administered jointly in different proportions in the hamster cheek pouch oral cancer model. The 3 assayed protocols were non-toxic, and showed preferential tumor boron uptake versus precancerous and normal tissue and therapeutic tumor boron concentration values (70–85 ppm). All 3 protocols warrant assessment in BNCT studies to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology for head and neck cancer and optimize therapeutic efficacy.

  18. Enhanced vesicular stomatitis virus (VSVΔ51 targeting of head and neck cancer in combination with radiation therapy or ZD6126 vascular disrupting agent

    Directory of Open Access Journals (Sweden)

    Alajez Nehad M

    2012-06-01

    Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC is the 5th most common cancer worldwide. Locally advanced HNSCC are treated with either radiation or chemo-radiotherapy, but still associated with high mortality rate, underscoring the need to develop novel therapies. Oncolytic viruses have been garnering increasing interest as anti-cancer agents due to their preferential killing of transformed cells. In this study, we evaluated the therapeutic potential of mutant vesicular stomatitis virus (VSVΔ51 against the human hypopharyngeal FaDu tumour model in vitro and in vivo. Results Our data demonstrated high toxicity of the virus against FaDu cells in vitro, which was associated with induction of apoptosis. In vivo, systemic injection of 1 × 109 pfu had minimal effect on tumour growth; however, when combined with two doses of ionizing radiation (IR; 5 Gy each or a single injection of the vascular disrupting agent (ZD6126, the virus exhibited profound suppression of tumour growth, which translated to a prolonged survival in the treated mice. Concordantly, VSVΔ51 combined with ZD6126 led to a significant increase in viral replication in these tumours. Conclusions Our data suggest that the combinations of VSVΔ51 with either IR or ZD6126 are potentially novel therapeutic opportunities for HNSCC.

  19. Biofilm imaging in porous media by laboratory X-Ray tomography: Combining a non-destructive contrast agent with propagation-based phase-contrast imaging tools.

    Science.gov (United States)

    Carrel, Maxence; Beltran, Mario A; Morales, Verónica L; Derlon, Nicolas; Morgenroth, Eberhard; Kaufmann, Rolf; Holzner, Markus

    2017-01-01

    X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent-biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development

  20. TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters

    International Nuclear Information System (INIS)

    Schneiderman, Rosa S; Shmueli, Esther; Kirson, Eilon D; Palti, Yoram

    2010-01-01

    Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin. Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line Emt R1 ; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs. TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells. The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors

  1. Enhanced cell killing and apoptosis of oral squamous cell carcinoma cells with ultrasound in combination with cetuximab coated albumin microbubbles.

    Science.gov (United States)

    Narihira, Kyoichi; Watanabe, Akiko; Sheng, Hong; Endo, Hitomi; Feril, Loreto B; Irie, Yutaka; Ogawa, Koichi; Moosavi-Nejad, Seyedeh; Kondo, Seiji; Kikuta, Toshihiro; Tachibana, Katsuro

    2018-03-01

    Targeted microbubbles have the potential to be used for ultrasound (US) therapy and diagnosis of various cancers. In the present study, US was irradiated to oral squamous cell carcinoma cells (HSC-2) in the presence of cetuximab-coated albumin microbubbles (CCAM). Cell killing rate with US treatment at 0.9 W/cm 2 and 1.0 W/cm 2 in the presence of CCAM was greater compared to non-targeted albumin microbubbles (p < .05). On the other hand, selective cell killing was not observed in human myelomonocytic lymphoma cell line (U937) that had no affinity to cetuximab. Furthermore, US irradiation in the presence of CCAM showed a fivefold increase of cell apoptotic rate for HSC-2 cells (21.0 ± 3.8%) as compared to U937 cells (4.0 ± 0.8%). Time-signal intensity curve in a tissue phantom demonstrated clear visualisation of CCAM with conventional US imaging device. Our experiment verifies the hypothesis that CCAM was selective to HSC-2 cells and may be applied as a novel therapeutic/diagnostic microbubble for oral squamous cell carcinoma.

  2. Combined effects of chronic hyperglycaemia and oral aluminium intoxication on testicular tissue and some male reproductive parameters in Wistar rats.

    Science.gov (United States)

    Akinola, O B; Biliaminu, S A; Adedeji, O G; Oluwaseun, B S; Olawoyin, O M; Adelabu, T A

    2016-09-01

    Exposure to either environmental toxicants or chronic hyperglycaemia could impair male reproductive function. However, the extent to which exposure to such toxicants, in the presence of pre-existing metabolic dysfunction, could affect male reproduction is unclear. Streptozotocin-induced diabetic Wistar rats (12 weeks old) were exposed to oral aluminium chloride at 250 ppm for 30 days; followed by evaluation of caudal epididymal sperm count and motility, assay for serum follicle stimulating hormone (FSH), testosterone (T) and oestradiol; and assessment of testicular histology. Moreover, blood glucose was evaluated by the glucose oxidase method. In rats treated with streptozotocin (STZ) or aluminium (Al) alone, erosion of testicular parenchyma and stroma was observed. This effect was most severe in diabetic rats simultaneously exposed to Al; coupled with reduced caudal epididymal sperm count that was least in this (STZ+Al) group (18.75 × 10(6)  ml(-1) ) compared with controls (61.25 × 10(6)  ml(-1) ; P < 0.05), STZ group or Al group. Moreover, these reproductive perturbations (in the STZ+Al group) were associated with reduced sperm motility and significantly reduced serum FSH (P < 0.05); but elevated serum T and oestradiol (P < 0.05), compared with control. These suggest that diabetes-induced testicular lesion is exacerbated by simultaneous oral Al toxicity in Wistar rats. © 2015 Blackwell Verlag GmbH.

  3. Effects of a diuretic and its combination with chelating agent on the removal of depleted uranium in rats

    International Nuclear Information System (INIS)

    Ikeda, Mizuyo; Fukuda, Satoshi; Nakamura, Mariko; Yoshida, Hiroki; Yan Xueming; Xie Yuyuan

    2008-01-01

    We examined the effects of a diuretic, isotonic saline, and chelating agent, catechol-3, 6-bis (methyleimiodiacetic acid) (CBMIDA), on the excretion and prevention of renal damage of depleted uranium (DU). Male Wistar rats (8 weeks old) divided into seven groups were preinjected intraperitoneally with 4 mg/kg DU and then the six groups were injected intraperitoneally with a diuretic, a diuretic plus isotonic saline, 480 mg/kg or 720 mg/kg CBMIDA alone, or 480 mg/kg or 720 mg/kg CBMIDA plus a diuretic and saline for three days, and the one group was as the control (no treatment). The rats were killed 6 days after DU injection. The results indicated that the diuretic alone and the diuretic with isotonic saline were not effective in removing uranium from the body and protecting the renal function, and also did not help to increase significantly the effects of CBMIDA. (author)

  4. Combined oral contraception and obesity are strong predictors of low-grade inflammation in healthy individuals: results from the Danish Blood Donor Study (DBDS.

    Directory of Open Access Journals (Sweden)

    Cecilie J Sørensen

    Full Text Available BACKGROUND: C-reactive protein (CRP is a well-established marker of inflammation. The level of CRP is affected by several lifestyle factors. A slightly increased CRP level, also known as low-grade inflammation (LGI, is associated with increased risk of several diseases, especially cardiovascular disease. The aim of this study was to identify predictors of increased CRP levels in healthy individuals. We therefore assessed CRP in a large cohort of blood donors. METHODS: We measured plasma CRP levels in 15,684 participants from the Danish Blood Donor Study. CRP was measured by a commercial assay. Furthermore, all participants completed a standard questionnaire on smoking status, alcohol consumption, physical activity, diet, and various body measurements. Female participants also reported the use of contraception, childbirth, and menopausal status. The relationship between LGI (defined here as a plasma CRP level between 3 mg/L and 10 mg/L and predictors was explored by multivariable logistic regression analysis. Results were presented as odds ratios (OR with 95% confidence intervals (CI. RESULTS: We found LGI in a total of 1,561 (10.0% participants. LGI was more frequent in women using combined oral contraception (OC (29.9% than in men (6.1% and women not using OC (7.9%. Among premenopausal women, OC was the strongest predictor of LGI (odds ratio = 8.98, p<0.001. Additionally, body mass index (BMI and waist circumference were positively associated with LGI. CONCLUSION: High BMI and abdominal obesity strongly predicted LGI among healthy individuals. However, the most striking finding was the high prevalence of LGI among premenopausal women who used combined oral contraception. Although the significance of CRP as a marker of inflammation is well known, the role of CRP in pathogenesis is still uncertain. The impact of oral contraception on CRP levels should nevertheless be considered when CRP is used in risk assessment.

  5. EXPERIENCE WITH THE ROSINSULIN C IN COMBINATION WITH ORAL ANTIDIABETIC DRUGS IN PATIENTS WITH TYPE 2 DIABETES IN ROUTINE CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    O. D. Rymar

    2014-01-01

    Full Text Available This study aimed to estimate the efficacy and safety of intermediate-acting insulin Rosinsulin C in patients with type 2 diabetes mellitus inadequately controlled with oral antidiabetic drugs.The present study is a 6-month, prospective, uncontrolled, clinical experience evaluation study using insulin Rosinsulin С for type 2 diabetes patients in daily clinical practice. Episodes of hypoglycaemia, adverse events were recorded. The study included 28 patients with type 2 diabetes, 4 men and 24 women who treated with metformin in combination with sulfonylureas in the highest dose. Indicators of glycosylated hemoglobin (HbA1c of 8 to 14%, the median HbA1c was 11 (10; 13% of patients age 65 (57; 72 years, body mass index – 33 (30; 35 kg/m2, waist circumference – 105 (99; 111 cm, diabetes duration – 7 (2; 11 years. With the introduction of Rosinsulin С cartridges carried pen Autopen. At the start of the study and after 3 and 6 months, determined the level of HbA1c, fasting plasma glucose.After 6 months' treatment with Rosinsulin С in combination with oral antidiabetic drugs HbA1c was significantly lowered (–3% (p = 0,001, fasting plasma glucose level decreased by 5 mmol/L (p = 0,001. There was not severe hypoglycemia during the observation period.This research showed that Rosinsulin C is effective and safe in the treatment of patients with type 2 diabetes who were decompensated with oral antidiabetic drugs and can be recommended for use as the initiation of insulin therapy in routine clinical practice.

  6. Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

    Science.gov (United States)

    Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

    2016-09-01

    The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

  7. The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease.

    Science.gov (United States)

    Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

    2015-01-01

    Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days' treatment. after 30 days' treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (Pmagnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function.

  8. Results of the intestitial brachytherapy and of the combination external radiation-brachytherapy in 150 patients with carcinoma of the oral tongue and floor of the mouth

    International Nuclear Information System (INIS)

    Sannazzari, G.L.; Negri, G.L.; Ozzello, F.

    1986-01-01

    The authors report their experience on the treatment of carcinoma of the oral tongue and floor of the mouth with interstitial brachytherapy, alone or in conbination with external irradiation. One hundred and fifty patients were treated; among these, 116 with brachytherapy alone, 34 with combined treatment. The five years local control in those patients treated with brachytherapy alone was 72.5% in T1, 61.2% in T2 and 35% in T3; in those patients treated with external irradiation and brachytherapy the global five years control was 42.5%. The global five years survival was 64% in the patients treated with brachytherapy alone 48% in the patients treated with combined therapy

  9. Results of the intestitial brachytherapy and of the combination external radiation-brachytherapy in 150 patients with carcinoma of the oral tongue and floor of the mouth

    Energy Technology Data Exchange (ETDEWEB)

    Sannazzari, G L; Negri, G L; Ozzello, F

    1986-01-01

    The authors report their experience on the treatment of carcinoma of the oral tongue and floor of the mouth with interstitial brachytherapy, alone or in conbination with external irradiation. One hundred and fifty patients were treated; among these, 116 with brachytherapy alone, 34 with combined treatment. The five years local control in those patients treated with brachytherapy alone was 72.5% in T1, 61.2% in T2 and 35% in T3; in those patients treated with external irradiation and brachytherapy the global five years control was 42.5%. The global five years survival was 64% in the patients treated with brachytherapy alone 48% in the patients treated with combined therapy. 42 refs.

  10. Immune responses induced in rabbits after oral administration of bovine serum albumin in combination with different adjuvants (herb extracts, aluminium hydroxide and platinum nanoparticles

    Directory of Open Access Journals (Sweden)

    G. Bižanov

    2016-12-01

    Full Text Available The aim of the current study was to evaluate the immunostimulatory activity of 10 different herbal extracts from Vitex agnus-castus, Vinca major, Aloe arborescens and the polyherbal product containing extracts from Sambucus nigra, Primula versis, Pinus alba, Gentiana lutea, Cetraria islandica, Eucaliptus globulus, Citrus limon and aluminium hydroxide, as well as platinum nanoparticles. Rabbits were immunized three times orally with bovine serum albumin (BSA in combination with the components mentioned above. BSA-specific IgA antibodies in saliva and IgG antibodies in serum were examined by ELISA. It was found that the rabbits immunized with BSA in combination with either platinum nanoparticles or aluminium hydroxide had higher titres of BSA-specific IgA antibodies in their saliva at day 56 of observation. Likewise, rabbits treated with BSA and Vinca major or Aloe arborescens extracts showed higher levels of BSA-specific IgG antibodies in the serum at the end of observation. These results suggest that some plant extracts, aluminium hydroxide and platinum nanoparticles components could be used as oral adjuvants or as immunomodulators for rabbits.

  11. Combined use of phospholipid complexes and self-emulsifying microemulsions for improving the oral absorption of a BCS class IV compound, baicalin

    Directory of Open Access Journals (Sweden)

    Huiyi Wu

    2014-06-01

    Full Text Available The aim of this study was to develop a formulation to improve the oral absorption of baicalin (BA by combining a phospholipid complex (PC and self-emulsifying microemulsion drug delivery system (SMEDDS, termed BA–PC–SMEDDS. BA–PC was prepared by a solvent evaporation method and evaluated by complexation percentage (CP. The physicochemical properties of BA–PC were determined. The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model. The improved bioavailability of BA in BA–PC–SMEDDS was confirmed in an in vivo rat model. The CP of BA–PC reached 100% when the molar ratio of drug to phospholipid (PP was ≥1:1. The solubility of BA–PC increased in both water and octanol, and the log Po/w of BA–PC was increased significantly. BA–PC–SMEDDS could be dispersed more evenly in water, compared to BA and BA–PC. Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA–PC was lower than that of free BA, while improved significantly in BA–PC–SMEDDS. The relative bioavailability of BA–PC(1:2–SMEDDS was 220.37%. The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.

  12. Exposure to an organophosphate pesticide, individually or in combination with other Gulf War agents, impairs synaptic integrity and neuronal differentiation, and is accompanied by subtle microvascular injury in a mouse model of Gulf War agent exposure.

    Science.gov (United States)

    Ojo, Joseph O; Abdullah, Laila; Evans, James; Reed, Jon Mike; Montague, Hannah; Mullan, Michael J; Crawford, Fiona C

    2014-04-01

    Gulf War illness (GWI) is a currently untreatable multi-symptom disorder experienced by 1990-1991 Persian Gulf War (GW) veterans. The characteristic hallmarks of GWI include cognitive dysfunction, tremors, migraine, and psychological disturbances such as depression and anxiety. Meta-analyses of epidemiological studies have consistently linked these symptomatic profiles to the combined exposure of GW agents such as organophosphate-based and pyrethroid-based pesticides (e.g. chlorpyrifos (CPF) and permethrin (PER) respectively) and the prophylactic use of pyridostigmine bromide (PB) as a treatment against neurotoxins. Due to the multi-symptomatic presentation of this illness and the lack of available autopsy tissue from GWI patients, very little is currently known about the distinct early pathological profile implicated in GWI (including its influence on synaptic function and aspects of neurogenesis). In this study, we used preclinical models of GW agent exposure to investigate whether 6-month-old mice exposed to CPF alone, or a combined dose of CPF, PB and PER daily for 10 days, demonstrate any notable pathological changes in hippocampal, cortical (motor, piriform) or amygdalar morphometry. We report that at an acute post-exposure time point (after 3 days), both exposures resulted in the impairment of synaptic integrity (reducing synaptophysin levels) in the CA3 hippocampal region and altered neuronal differentiation in the dentate gyrus (DG), demonstrated by a significant reduction in doublecortin positive cells. Both exposures also significantly increased astrocytic GFAP immunoreactivity in the piriform cortex, motor cortex and the basolateral amygdala and this was accompanied by an increase in (basal) brain acetylcholine (ACh) levels. There was no evidence of microglial activation or structural deterioration of principal neurons in these regions following exposure to CPF alone or in combination with PB and PER. Evidence of subtle microvascular injury was

  13. The comparative study of side effect of the two kinds of LD combined oral contraceptive pills containing Norgestimate and Levonorgestrel

    Directory of Open Access Journals (Sweden)

    Ghazizade Sh

    1998-05-01

    Full Text Available In order to compare the new generation of oral contraceptive pills containing Norgestimate (NGM with currently available pills containing levonorgestrel (LNG a clinical trial was conducted. 413 women (age 18-35 years with no contrainindication to pill use entered the study and randomly received one type of pills. Premenstrual syndrome and depression were significantly decreased in NGM group (P=0.00016, P=0.005, on the other hand, breast tenderness, mood changes and hair loss were significantly increased in LNG group (P=0.001, P=0.042, P=0.011. Comparing two groups with each other, following variables were significantly lower in NGM group: headache (P<0.05, vertigo (P<0.05, cloasma (P<0.05, acne (P<0.04, depression (P<0.05, appetite change (P<0.03. Overall patient satisfaction was similar in two groups.

  14. No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide.

    Science.gov (United States)

    de la Peña, Amparo; Cui, Xuewei; Geiser, Jeanne; Loghin, Corina

    2017-11-01

    Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of type 2 diabetes mellitus are known to delay gastric emptying (GE). The potential effect of the GLP-1 RA dulaglutide on the pharmacokinetics (PK) of four orally administered drugs and on the pharmacodynamic (PD) effect of warfarin was investigated. In four separate clinical pharmacology studies, digoxin, warfarin, atorvastatin and Ortho-Cyclen ® were orally administered to healthy subjects with and without a subcutaneous dose of dulaglutide 1.5 mg. The effect of dulaglutide coadministration was assessed based on the PK parameters of key analytes. For warfarin PD, the effect of dulaglutide on the international normalized ratio (INR) was evaluated. Areas under the concentration-time curves (AUCs) with and without dulaglutide were similar for all analytes except atorvastatin, where it was reduced by 21%. Maximum concentrations (C max ) were generally lower following coadministration with dulaglutide, with statistically significant reductions (90% confidence intervals of geometric least squares means ratios outside 0.80-1.25) for all analytes except R-warfarin. For all analytes, there was a general trend for the time to C max (t max ) to increase following coadministration with dulaglutide. For warfarin, dulaglutide coadministration had no statistically significant effect on the maximum INR (INR max ); however, a 2% increase in area under the INR curve (AUC INR ) was observed. Dulaglutide did not affect the absorption of the tested medications to a clinically relevant degree. Based on the PK and PD evaluations, no dose adjustments for digoxin, warfarin, atorvastatin and Ortho-Cyclen ® are recommended when coadministered with dulaglutide. NCT01458210, NCT01436201, NCT01432938, and NCT01250834.

  15. Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

    Science.gov (United States)

    Dilrukshi, M D S A; Ratnayake, C A P; Gnanathasan, C A

    2017-08-08

    Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had

  16. Effect of fluorescent pseudomonades and Trichoderma sp. and their combination with two chemicals on Penicillium digitatum caused agent of citrus green mold.

    Science.gov (United States)

    Zamani, M; Tehrani, A Sharifi; Ahmadzadeh, M; Abadi, A Alizadeh Ali

    2006-01-01

    Citrus green mold (Penicillium digitatum) causes economic losses. Chemical fungicides such as imazalil provide the primary means for controlling green mold decay of citrus fruits. Continuous use of fungicides has faced two major obstacles- increasing public concern regarding contamination of perishables with fungicidal residues, and proliferation of resistance in the pathogen populations. The aim of this research was to determine if the attacks of green mold on orange could be reduced by usage of biocontrol agent alone or in combination with low dosage of imazalil or sodium bicarbonate. Pseudomonas fluorescens isolate PN, P. fluorescens isolate PS and Trichoderma virens isolate TE were evaluated as potential biological agents for control of green mold of oranges caused by P. digitatum. Increasing concentration of SB decreased spore germination of P. digitatum. In laboratory tests, a cell suspension (10(8) cells per ml.) of bacterial strains reduced the incidence of green mold. On fruits surface biocontrol activity of antagonistic isolates was significantly increased when combined with low dosage of imazalil (500ppm) or sodium carbonate (5%). Effect of Trichoderma virens on controlling P. digitatum was better than others with or without these chemicals.

  17. The combination of BH3-mimetic ABT-737 with the alkylating agent temozolomide induces strong synergistic killing of melanoma cells independent of p53.

    Directory of Open Access Journals (Sweden)

    Steven N Reuland

    Full Text Available Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2 family members, has been found to enhance the efficacy of many conventional chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT-737 induced strong synergistic apoptosis in multiple human melanoma cell lines. When the drugs were used in combination in a mouse xenograft model, they drastically reduced tumor growth at concentrations where each individual drug had no significant effect. We found that TMZ treatment elevated p53 levels, and that the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells. Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT-737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer, demonstrated that p53 induction was sufficient for synergistic cell death with ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT-737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737 together induce Noxa in a p53-independent fashion. These results demonstrate that targeting anti-apoptotic Bcl-2 members is a promising method for treating metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are warranted.

  18. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: Acceptability, tolerability and impact on the genital microbiota of couples - A pilot study.

    Science.gov (United States)

    Plummer, Erica L; Vodstrcil, Lenka A; Danielewski, Jennifer A; Murray, Gerald L; Fairley, Christopher K; Garland, Suzanne M; Hocking, Jane S; Tabrizi, Sepehr N; Bradshaw, Catriona S

    2018-01-01

    Bray-Curtis score day 0 vs day 8 = 0.09 [0.04-0.17]), however this was not as pronounced at day 28 (median Bray-Curtis score day 0 vs day 28 = 0.38 [0.11-0.59]). A decrease in the prevalence and abundance of BV-associated bacteria in the cutaneous penile microbiota was observed immediately following treatment at day 8. Combined oral and topical treatment of male partners of women with BV is acceptable and well tolerated. The combined acceptability and microbiological data presented in this paper supports the need for larger studies with longer follow up to characterize the sustained effect of dual partner treatment on the genital microbiota of couples and assess the impact on BV recurrence.

  19. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: Acceptability, tolerability and impact on the genital microbiota of couples - A pilot study.

    Directory of Open Access Journals (Sweden)

    Erica L Plummer

    microbiota (median Bray-Curtis score day 0 vs day 8 = 0.09 [0.04-0.17], however this was not as pronounced at day 28 (median Bray-Curtis score day 0 vs day 28 = 0.38 [0.11-0.59]. A decrease in the prevalence and abundance of BV-associated bacteria in the cutaneous penile microbiota was observed immediately following treatment at day 8.Combined oral and topical treatment of male partners of women with BV is acceptable and well tolerated. The combined acceptability and microbiological data presented in this paper supports the need for larger studies with longer follow up to characterize the sustained effect of dual partner treatment on the genital microbiota of couples and assess the impact on BV recurrence.

  20. Interacción de los antineoplásicos orales con los alimentos: revisión sistemática Antineoplastic oral agents and drug-nutrient interactions: a sistematic review

    OpenAIRE

    N. V. Jiménez Torres; I. Romero Crespo; M. Ballester Solaz; A. Albert Marí; V. Jiménez Arenas

    2009-01-01

    Introducción: Los estudios de biodisponibilidad son parte integrante del desarrollo clínico de medicamentos para administración oral con el fin de identificar potenciales interacciones fármaco-alimento (iFA). Actualmente, para los antineoplásicos orales se empieza a reconocer su importancia clínica, aun cuando lamentablemente, la información disponible presenta variabilidad en su evidencia científica. Objetivos: Revisar la evidencia científica disponible sobre las interacciones de los aliment...

  1. Cytotoxicity and cell-cycle effects of paclitaxel when used as a single agent and in combination with ionizing radiation

    International Nuclear Information System (INIS)

    Gupta, Nalin; Hu, Lily J.; Deen, Dennis F.

    1997-01-01

    Purpose: This study aimed to determine the extent of paclitaxel-induced cytotoxicity and cell-cycle perturbations when used alone and in combination with radiation in human glioma cells. Methods and Materials: The effect of paclitaxel alone on three human glioma cells lines--SF-126, U-87 MG, and U-251 MG--was assessed after 24, 48, 72, or 96 h treatment. For experiments in combination with radiation, cells were exposed to either a long (48-h) or short (8-h) duration of paclitaxel treatment prior to irradiation. Cell survival was determined by clonogenic assay. Cell cycle perturbations were assessed by using flow cytometry to measure the proportion of cells in G 1 , S, and G 2 /M phases. Results: When cells were treated with paclitaxel alone for ≥24 h, cytotoxicity increased up to a threshold dose, after which it plateaued. When treatment duration was ≤24 h, cytotoxicity was appreciably greater in U-251 MG cells than in SF-126 and U-87 MG cells. After 24 h of paclitaxel treatment, cells in plateau phase growth had increased survival compared to cells in log phase growth. In contrast, after 8 h paclitaxel treatment, mitotic cells had reduced survival compared to cells from an asynchronous population. Cell-cycle perturbations were consistent with the presence of a mitotic block after paclitaxel treatment, although changes in other cell-cycle phase fractions varied among cell lines. For experiments in combination with radiation, cytotoxicity was increased when cells were irradiated after 48 h of paclitaxel treatment but not after 8 h of treatment. Conclusion: The duration of paclitaxel treatment and the location of cells in the cell cycle modify the degree of radiation cytotoxicity. The mechanisms of paclitaxel cytotoxicity are likely to be multifactorial because varying effects are seen in different cell lines. Furthermore, it is clear that simply increasing the number of cells in G 2 /M is insufficient in itself to increase the response of cells to radiation

  2. Synthesis and Physicochemical Characterization of a Diethyl Ester Prodrug of DTPA and Its Investigation as an Oral Decorporation Agent in Rats.

    Science.gov (United States)

    Huckle, James E; Sadgrove, Matthew P; Leed, Marina G D; Yang, Yu-Tsai; Mumper, Russell J; Semelka, Richard C; Jay, Michael

    2016-07-01

    The increasing threats of nuclear terrorism have made the development of medical countermeasures a priority for international security. Injectable formulations of diethylenetriaminepentaacetic acid (DTPA) have been approved by the FDA; however, an oral formulation is more amenable in a mass casualty situation. Here, the diethyl ester of DTPA, named C2E2, is investigated for potential as an oral treatment for internal radionuclide contamination. C2E2 was synthesized and characterized using NMR, MS, and elemental analysis. The physiochemical properties of solubility, lipophilicity, and stability were investigated in order to predict its oral bioavailability. Finally, an animal efficacy study was conducted in Sprague Dawley rats pre-contaminated by intramuscular injection with (241)Am(NO3)3 to establish effectiveness of the therapy via the oral route. Synthesis of C2E2 yielded a crystalline powder with high solubility and improved lipophilicity over DTPA. The ester was stable in both simulated gastric and intestinal fluids over the anticipated time course of absorption. Capsules containing C2E2 were demonstrated to be stable for 12 months under accelerated stability conditions. After a single dose, C2E2 enhanced the elimination of (241)Am in a dose-dependent manner. Significant improvement was seen in both total (241)Am decorporation and reduction of (241)Am liver and skeletal burden. C2E2 was concluded to be effective when orally administered to (241)Am-contaminated rats. It may therefore have potential for medical countermeasure in treating humans contaminated with (241)Am or other transuranic elements. An oral capsule or powder for reconstitution may be suitable formulations for future development based on the physiochemical properties and anticipated dose required for efficacy.

  3. SU-E-T-256: Optimizing the Combination of Targeted Radionuclide Therapy Agents Using a Multi-Scale Patient-Specific Monte Carlo Dosimetry Platform

    International Nuclear Information System (INIS)

    Besemer, A; Bednarz, B; Titz, B; Grudzinski, J; Weichert, J; Hall, L

    2014-01-01

    Purpose: Combination targeted radionuclide therapy (TRT) is appealing because it can potentially exploit different mechanisms of action from multiple radionuclides as well as the variable dose rates due to the different radionuclide half-lives. The work describes the development of a multiobjective optimization algorithm to calculate the optimal ratio of radionuclide injection activities for delivery of combination TRT. Methods: The ‘diapeutic’ (diagnostic and therapeutic) agent, CLR1404, was used as a proof-of-principle compound in this work. Isosteric iodine substitution in CLR1404 creates a molecular imaging agent when labeled with I-124 or a targeted radiotherapeutic agent when labeled with I-125 or I-131. PET/CT images of high grade glioma patients were acquired at 4.5, 24, and 48 hours post injection of 124I-CLR1404. The therapeutic 131I-CLR1404 and 125ICLR1404 absorbed dose (AD) and biological effective dose (BED) were calculated for each patient using a patient-specific Monte Carlo dosimetry platform. The optimal ratio of injection activities for each radionuclide was calculated with a multi-objective optimization algorithm using the weighted sum method. Objective functions such as the tumor dose heterogeneity and the ratio of the normal tissue to tumor doses were minimized and the relative importance weights of each optimization function were varied. Results: For each optimization function, the program outputs a Pareto surface map representing all possible combinations of radionuclide injection activities so that values that minimize the objective function can be visualized. A Pareto surface map of the weighted sum given a set of user-specified importance weights is also displayed. Additionally, the ratio of optimal injection activities as a function of the all possible importance weights is generated so that the user can select the optimal ratio based on the desired weights. Conclusion: Multi-objective optimization of radionuclide injection activities

  4. Combination therapy with biofeedback, loperamide, and stool-bulking agents is effective for the treatment of fecal incontinence in women - a randomized controlled trial.

    Science.gov (United States)

    Sjödahl, Jenny; Walter, Susanna A; Johansson, Elin; Ingemansson, Anna; Ryn, Ann-Katrine; Hallböök, Olof

    2015-08-01

    Biofeedback and medical treatments have been extensively used for moderate fecal incontinence (FI). There is limited data comparing and combining these two treatments. The objective of this study was to evaluate the effect of biofeedback and medical treatments, separately and in combination. Sixty-four consecutive female patients, referred to a tertiary centre for FI, were included. The patients were randomized to start with either biofeedback (4-6 months) or medical treatment with loperamide and stool-bulking agents (2 months). Both groups continued with a combination of treatments, i.e. medical treatment was added to biofeedback and vice versa. A two-week prospective bowel symptom diary and anorectal physiology were evaluated at baseline, after single- and combination treatments. Fifty-seven patients completed the study. Median number of leakage episodes during two weeks decreased from 6 to 3 (p biofeedback and medical treatment is effective for symptom relief in FI. The symptom improvement was associated with improved fecal consistency, reduced urgency, and increased rectal sensory thresholds.

  5. Does current oral antiplatelet agent or subtherapeutic anticoagulation use have an effect on tissue-plasminogen-activator-mediated recanalization rate in patients with acute ischemic stroke?

    Science.gov (United States)

    Ibrahim, Mohamed M; Sebastian, Joseph; Hussain, Muhammad; Al-Hussain, Fawaz; Uchino, Ken; Molina, Carlos; Khan, Khurshid; Demchuk, Andrew M; Alexandrov, Andrei V; Saqqur, Maher

    2010-01-01

    Our goal is to assess if current antiplatelet (AP) use has an effect on recanalization rate and outcome in acute stroke patients. We conducted a retrospective analysis of acute stroke patients who received intravenous (IV) recombinant tissue plasminogen activator (rt-PA) and had transcranial Doppler examination within 3 h of symptom onset. The TCD findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion or complete recanalization. Complete recanalization was defined as established Thrombolysis in Brain Ischemia 4 or 5 within 2 h of IV rt-PA. The patients were divided based on their current use of AP agents. Comparisons were made between the different groups based on recanalziation rate, reocclusion and good long-term outcome (mRS ≤ 2) using χ(2) test. Multiple regression analysis was used to identify AP use as a predictor for recanalization and outcome including symptomatic intracranial hemorrhage after controlling for age, baseline NIHSS score, time to treatment, previous vascular event, hypertension and diabetes mellitus. Two hundred and eighty-four patients were included; 154 (54%) males, 130 (46%) females, with a mean age of 69.5 ± 13 years. The median baseline NIHSS score was 16 ± 5. The median time to TCD examination was 131 ± 38 min from symptom onset. The median time to IV rt-PA was 140 ± 34 min. One hundred eighty patients were not on AP prior to their stroke, 76 were on aspirin, 15 were on clopidogrel, 2 were on aspirin-dipyridamole combination, 2 were on both aspirin and clopidogrel, and 9 patients on subtherapeutic coumadin. In patients who were naïve to AP, 68/178 (38.2%) had complete recanalization, whereas in the AP group, 25/91 (28%) had complete recanalization. Patients on aspirin alone had a lower recanalization rate (16/72) as compared to those not on AP (22 vs. 39%) (p = 0.017), while those on clopidogrel had higher rates of complete recanalization (9/19, 60

  6. Investigation on the association between breast cancer and consumption patterns of combined oral contraceptive pills in the women of Isfahan in 2011.

    Science.gov (United States)

    Ehsanpour, Soheila; Nejad, Fahime Seyed Ahmadi; Rajabi, Fariborz Mokarian; Taleghani, Fariba

    2013-05-01

    Oral contraceptive pills are among the most popular contraceptive methods, but the fear of cancer and cardiovascular disease overshadows its continuous use among women. This study aimed to define the association between consumption patterns of combined oral contraceptives among women with breast cancer. This is an analytical case-control study conducted on 175 women with breast cancer, referring to Seyed al Shohada Medical Center and private clinics in Isfahan to be treated and followed up in 2011, as well as 350 healthy women who were identical with the subjects in the study group regarding age and residential location. The data were collected using a researcher-made questionnaire. Content validity and Cronbach's alpha were employed to confirm validity and scientific reliability of the questionnaire, respectively. The data were analyzed by descriptive and analytical statistical methods through SPSS. The findings showed that there was a significant association between history of contraceptive pills' consumption and incidence of breast cancer (P pills' consumption compared to those with no history of that. It was also shown that pills' consumption for 36-72 months increased the risk of breast cancer by 2.18-fold, the age of the first use being less than 20 years increased the risk by 3.28-fold, and time since the last use of less than 25 years increased the risk by 2.63-fold. There was no significant association between duration of use, age of the first and last use, and time since the first and last use in the study and control groups. The results showed that history of pills' consumption is associated with incidence of breast cancer regardless of the consumption pattern. Use of oral contraceptives pills at any age and for any duration can increase the risk of breast cancer.

  7. Combined-modality treatment in advanced oral squamous cell carcinoma. Primary surgery followed by adjuvant concomitant radiochemotherapy

    International Nuclear Information System (INIS)

    Kreppel, Matthias; Dreiseidler, Timo; Zoeller, Joachim E.; Scheer, Martin; Drebber, Uta; Eich, Hans-Theodor; Mueller, Rolf-Peter

    2011-01-01

    The efficacy of adjuvant radiochemotherapy (RCT) in patients with advanced stage head and neck carcinoma has been proven in prospective randomized trials. However, these trials focused on different head and neck sites. Specific analyses for treatment effects in squamous cell carcinoma of the oral cavity (OSCC) are missing. We evaluated our experiences with adjuvant concomitant RCT in advanced OSCC to compare the results with other treatment schemes using adjuvant RCT. A total of 183 patients with OSCC of UICC stages II-IVb were reviewed retrospectively. All patients were treated with radical surgery followed by adjuvant, conventional fractionated concomitant RCT using carboplatin. Overall survival was plotted by Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analysis. Univariate analysis showed a significant impact of T, N, and UICC stage, histopathologic grading, surgical margins, extracapsular spread (ECS), and lymphangiosis carcinomatosa on overall survival (Table 3). Patients with stage IVa had a higher 5-year overall survival rate (42.8%) than patients with stage IVb (25.0%) (Figure 1). The differences were significant in multivariate analysis (p = 0.033) (Table 4). Adjuvant concomitant RCT is an effective treatment in patients with advanced stage OSCC. However, it remains unclear, which patients should be treated with adjuvant RCT. For patients with stage IVb, adjuvant RCT yields poor results. Prospective randomized trials are needed to confirm which patients should be treated with adjuvant RCT. (orig.)

  8. Combined Effect of Synthetic and Natural Polymers in Preparation of Cetirizine Hydrochloride Oral Disintegrating Tablets: Optimization by Central Composite Design.

    Science.gov (United States)

    Patro, Chandra Sekhar; Sahu, Prafulla Kumar

    2017-01-01

    Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs) by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS) and natural Hibiscus rosa-sinensis mucilage (HRM) as disintegrants in the formulation. Central composite design (CCD) was applied to optimize the influence of three levels each of CCS ( X 1 ) and HRM ( X 2 ) concentrations (independent variables) for investigated responses: disintegration time (DT) ( Y 1 ), % friability ( F ) ( Y 2 ), and % cumulative drug release (DR) ( Y 3 ) (dependent variables). This face-centered second-order model's reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses' sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR) and thermograms from Differential Scanning Calorimetry (DSC) demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.

  9. Combined Effect of Synthetic and Natural Polymers in Preparation of Cetirizine Hydrochloride Oral Disintegrating Tablets: Optimization by Central Composite Design

    Directory of Open Access Journals (Sweden)

    Chandra Sekhar Patro

    2017-01-01

    Full Text Available Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS and natural Hibiscus rosa-sinensis mucilage (HRM as disintegrants in the formulation. Central composite design (CCD was applied to optimize the influence of three levels each of CCS (X1 and HRM (X2 concentrations (independent variables for investigated responses: disintegration time (DT (Y1, % friability (F (Y2, and % cumulative drug release (DR (Y3 (dependent variables. This face-centered second-order model’s reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses’ sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR and thermograms from Differential Scanning Calorimetry (DSC demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.

  10. Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease

    Science.gov (United States)

    Assy, Nimer; Grozovski, Masha; Bersudsky, Ilana; Szvalb, Sergio; Hussein, Osamah

    2006-01-01

    AIM: To assess whether treatment with insulin-sensitizing agents (ISAs) in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet (MCDD) rat model of non-alcoholic fatty liver disease (NAFLD). METHODS: Rats (n = 6 per group) were treated with different drugs, including MCDD only, MCDD diet with either metformin (200 mg/kg), rosiglitazone (3 mg/kg), metformin plus rosiglitazone (M+R), ezetimibe (2 mg/kg), valsartan (2 mg/kg), or combination of all drugs for a total of 15 wk. Liver histology, lipids, parameters of oxidative stress and TNF-alpha were measured. RESULTS: Fatty liver (FL) rats demonstrated severe hepatic fatty infiltration (> 91% fat), with an increase in hepatic TG (+1263%, P < 0.001), hepatic cholesterol (+245%, P < 0.03), hepatic MDA levels (+225%, P < 0.001), serum TNF-alpha (17.8 ± 10 vs 7.8 ± 0.0, P < 0.001), but a decrease in hepatic alpha tocopherol (-74%, P < 0.001) as compared to the control rats. Combination therapy with all drugs produced a significant decrease in liver steatosis (-54%), hepatic TG (-64%), hepatic cholesterol (-31%) and hepatic MDA (-70%), but increased hepatic alpha tocopherol (+443%) as compared to FL rats. Combination therapy with ISA alone produced a smaller decrease in liver steatosis (-32% vs -54%, P < 0.001) and in hepatic MDA levels (-55% vs -70%, P < 0.01), but a similar decrease in hepatic lipids when compared with the all drugs combination. TNF-alpha levels decreased significantly in all treatment groups except in ISA group. CONCLUSION: Combination therapies have a greater effect on liver fat content as compared to monotherapy. Rosiglitazone appears to improve hepatic steatosis to a greater extent than metformin. PMID:16865780

  11. Combined treatment with oral finasteride and topical minoxidil in male androgenetic alopecia: a randomized and comparative study in Chinese patients.

    Science.gov (United States)

    Hu, Ruiming; Xu, Feng; Sheng, Youyu; Qi, Sisi; Han, Yumei; Miao, Ying; Rui, Wenlong; Yang, Qinping

    2015-01-01

    Finasteride at 1 mg/day and 5% topical minoxidil are effective in male androgenetic alopecia (MAGA). However, studies describing their effects in Chinese individuals are scarce. 450 Chinese MAGA patients were randomly assigned to receive finasteride (n = 160), minoxidil (n = 130) and combined medication (n = 160) for 12 months. The patients returned to the clinic every 3 months for efficacy evaluation. And efficacy was evaluated in 428 men at treatment end, including 154, 122, and 152 in the finasteride, 5% minoxidil, and combination groups, respectively. All groups showed similar baseline characteristics, including age at enrollment, and duration and severity of alopecia (p > 0.05). At 12 months, 80.5, 59, and 94.1% men treated with finasteride, 5% minoxidil and the combination therapy showed improvement, respectively. Adverse reactions were rare (finasteride, 1.8%; minoxidil, 6.1%), and disappeared right after drug withdrawal. In conclusion, finasteride is superior to 5% minoxidil, while the combined medication showed the best efficacy. © 2015 Wiley Periodicals, Inc.

  12. Low-cost fabrication of ternary CuInSe{sub 2} nanocrystals by colloidal route using a novel combination of volatile and non-volatile capping agents

    Energy Technology Data Exchange (ETDEWEB)

    Chawla, Parul; Narain Sharma, Shailesh, E-mail: shailesh@nplindia.org; Singh, Son

    2014-11-15

    Wet-route synthesis of CuInSe{sub 2} (CISe) nanocrystals has been envisaged with the utilization of the unique combination of coordinating ligand and non coordinating solvent. Our work demonstrates the formation of a single-phase, nearly stoichiometric and monodispersive, stable and well-passivated colloidal ternary CISe nanocrystals (band gap (E{sub g})∼1.16 eV) using a novel combination of ligands; viz. volatile arylamine aniline and non-volatile solvent 1-octadecene. The synthesis and growth conditions have been manoeuvred using the colligative properties of the mixture and thus higher growth temperature (∼250 °C) could be attained that promoted larger grain growth. The beneficial influence of the capping agents (aniline and 1-octadecene) on the properties of chalcopyrite nanocrystals has enabled us to pictorally model the structural, morphological and optoelectronic aspects of CISe nanoparticles. - Graphical abstract: Without resorting to any post-selenization process and using the colligative properties of the mixture comprising of volatile aniline and non-volatile 1-octadecene to manoeuvre the growth conditions to promote Ostwald ripening, a single phase, monodispersive and nearly stoichiometric ternary CISe nanocrystals are formed by wet-synthesis route. - Highlights: • Wet-route synthesis of CISe nanocrystals reported without post-selenization process. • Single-phase, stable and well-passivated colloidal ternary CISe nanocrystals formed. • Novel combination of capping agents: volatile aniline and non-volatile 1-octadecene. • Higher growth temperature attained using the colligative properties of the mixture. • Metallic salts presence explains exp. and theoretical boiling point difference.

  13. Utilization of a selective tumour artery catheterization technique for the intra-arterial delivery of chemotherapeutic agents and radiopharmaceuticals in a combined chemotherapy-radiotherapy clinical research programme

    International Nuclear Information System (INIS)

    Wiley, A.L. Jr.; Wirtanen, G.W.; Holden, J.E.; Polcyn, R.E.

    1977-01-01

    Combined intra-arterial chemotherapeutic agents (principally actinomycin-D) and radiation therapy has been utilized in the treatment of 35 patients with massive unresectable malignancies. The goals may be separated into three distinct categories. An attempt has been made to convert unresectable malignancies to surgical resectability, to provide a definitive therapy for massive tumours in patients who either refuse surgery or are not surgery candidates, and to provide palliation. Twelve of 15 initially unresectable tumours treated with actinomycin-D became surgically resectable (no resection was attempted in the other four because they either developed metastasis during therapy or did not complete the therapy), 4 of 6 massive tumours treated definitively have remained locally controlled from 18 to 108 months, and 7 of 9 patients treated palliatively were significantly benefited by the therapy. Impressive responses were also achieved in several patients treated with intra-arterial 5-fluorouracil and 5-iodo-2'-deoxyuridine. The authors therefore consider combined, concurrent radiation therapy and intra-arterially administered chemotherapeutic agents worthy of further clinical investigation as a means of treating massive malignancies. They also suggest that the best chance of optimizing the therapeutic ratio of such therapy is dependent primarily on a proper understanding of clinical tumour vascularity and of its subsequent effect on drug and oxygen distributions within the radiation treatment volume. Accordingly, tumour vascularity has been clinically evaluated by the use of intra-arterially administered radiopharmaceuticals. Such clinical data, in conjunction with radiobiological data, might in the future be utilized to optimize both low and high LET combined therapy by allowing for correction of the physical isodose for drug and oxygen concentration variations. (author)

  14. Effects of cytochalasin congeners, microtubule-directed agents, and doxorubicin alone or in combination against human ovarian carcinoma cell lines in vitro

    International Nuclear Information System (INIS)

    Trendowski, Matthew; Christen, Timothy D.; Acquafondata, Christopher; Fondy, Thomas P.

    2015-01-01

    Although the actin cytoskeleton is vital for carcinogenesis and subsequent pathology, no microfilament-directed agent has been approved for cancer chemotherapy. One of the most studied classes of microfilament-directed agents has been the cytochalasins, mycotoxins known to disrupt the formation of actin polymers. In the present study, we sought to determine the effects of cytochalasin congeners toward human drug sensitive and multidrug resistant cell lines. SKOV3 human ovarian carcinoma and several multidrug resistant derivatives were tested for sensitivity against a panel of nine cytochalasin congeners, as well as three clinically approved chemotherapeutic agents (doxorubicin, paclitaxel, and vinblastine). In addition, verapamil, a calcium ion channel blocker known to reverse P-glycoprotein (P-gp) mediated drug resistance, was used in combination with multiple cytochalasin congeners to determine whether drug sensitivity could be increased. While multidrug resistant SKVLB1 had increased drug tolerance (was more resistant) to most cytochalasin congeners in comparison to drug sensitive SKOV3, the level of resistance was 10 to 1000-fold less for the cytochalasins than for any of the clinically approved agents. While cytochalasins did not appear to alter the expression of ATP binding cassette (ABC) transporters, several cytochalasins appeared to inhibit the activity of ABC transporter-mediated efflux of rhodamine 123 (Rh123), suggesting that these congeners do have affinity for drug efflux pumps. Cytochalasins also appeared to significantly decrease the F/G-actin ratio in both drug sensitive and drug resistant cells, indicative of marked microfilament inhibition. The cytotoxicity of most cytochalasin congeners could be increased with the addition of verapamil, and the drug sensitivity of resistant SKVLB1 to the clinically approved antineoplastic agents could be increased with the addition of cytochalasins. As assessed by isobolographic analysis and Chou

  15. Biopsy Diagnosis of Oral Carcinoma by the Combination of Morphological and Spectral Methods Based on Embedded Relay Lens Microscopic Hyperspectral Imaging System.

    Science.gov (United States)

    Ou-Yang, Mang; Hsieh, Yao-Fang; Lee, Cheng-Chung

    Cytopathological examination through biopsy is very important for carcinoma detection. The embedded relay lens microscopic hyperspectral imaging system (ERL-MHIS) provides a morphological image of a biopsy sample and the spectrum of each pixel in the image simultaneously. Based on the ERL-MHIS, this work develops morphological and spectral methods to diagnose oral carcinoma biopsy. In morphological discrimination, the fractal dimension method is applied to differentiate between normal and abnormal tissues. In spectral identification, normal and cancerous cells are distinguished using five methods. However, the spectra of normal and cancerous cells vary with patient. The diagnostic performances of the five methods are thus not ideal. Hence, the proposed cocktail approach is used to determine the effectiveness of the spectral methods in correlating with the sampling conditions. And then we use a combination of effective spectral methods according to the sample conditions for diagnosing a sample. A total of 68 biopsies from 34 patients are analyzed using the ERL-MHIS. The results demonstrate a sensitivity of 90 ± 4.53 % and a specificity of 87.8 ± 5.21 %. Furthermore, in our survey, this system is the first time utilized to study oral carcinoma biopsies.

  16. Comparative clinical trial of artesunate suppositories and oral artesunate in combination with mefloquine in the treatment of children with acute falciparum malaria.

    Science.gov (United States)

    Sabchareon, A; Attanath, P; Chanthavanich, P; Phanuaksook, P; Prarinyanupharb, V; Poonpanich, Y; Mookmanee, D; Teja-Isavadharm, P; Heppner, D G; Brewer, T G; Chongsuphajaisiddhi, T

    1998-01-01

    A randomized pilot study to compare the safety and efficacy of artesunate suppositories (15 mg/kg/day for three days) versus oral artesunate (6 mg/kg/day for three days), both in combination with mefloquine (25 mg/kg), was conducted in 52 Thai children with uncomplicated multidrug-resistant falciparum malaria. Forty-five patients (87%) had a full 28-day follow-up in the hospital to assess efficacy and exclude reinfection. Mean [range] times to fever clearance of the two groups were similar (42 hr [15-104] versus 42 hr [6-119]). Artesunate suppositories resulted in significantly longer times to achieve 50% and 90% reductions of the initial parasite counts (17 and 26 hr versus 9 and 15 hr; P suppositories group (42 hr [14-93] versus 35 hr [16-69]), but the difference was not significant. The cure rates by days 28 were not significantly different, 92% for artesunate suppository-treated patients and 100% for oral artesunate-treated patients. Both drug regimens are safe and effective. Further studies are needed to characterize the pharmacokinetic properties and the optimum regimen of artesunate suppositories for the treatment of severe malaria.

  17. Removal of inhaled 241Am oxide particles from beagle dogs by combined treatment with lung lavage and a chelating agent

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mewhinney, J.A.; Mo, T.; Slauson, D.O.

    1978-01-01

    This experiment was performed to evaluate combined therapy of lung lavage and chelation treatments to remove inhaled particles of 241 Am oxide. Twenty-four Beagle dogs were divided into four groups of 6 dogs each. Each group was exposed to an aerosol of different-sized particles of 241 Am oxide: monodisperse particles with AD of 0.75, 1.5 or 3.0 μm; polydisperse particles with AMAD = 1.5 μm. Three dogs in each group were treated with 5 lung lavages of the right lung (day 2, 7, 14, 28 and 42), and 5 lavages of the left lung (days 2, 10, 21, 35, and 49). In addition, each of the treated dogs was given 22 μmoles of trisodium calcium diethylenetriaminepentaacetate (Na 3 Ca DTPA) by intravenous injection 18 times from day 1 to 52 after exposure. The remaining 3 dogs in each group were untreated control dogs. All of the dogs were sacrificed 64 days after exposure and tissues, excreta, and lavage fluids were analyzed for 241 Am activity. Tissue distribution of 241 Am activity at sacrifice varied with aerosol particle size. Less 241 Am activity was found in the lungs of the dogs exposed to 0.75 and 1.5 μm AD aerosols groups than in those exposed to 3.0 μm particles. Lung lavage removed from 24 to 58% of the initial lung burden (ILB). Particle size did not affect the usefulness of lung lavage but it did influence the effectiveness of Na 3 Ca DTPA treatment. Na 3 Ca DTPA enhanced urinary excretion of 241 Am; dogs exposed to 0.75 μm particles excreted 31% of the ILB, and those exposed to 3.0 μm particles excreted only 10%. This experiment showed the effectiveness of combined treatment with lung lavage and chelation therapy for the removal of 241 Am oxide in the first 64 days after exposure. (author)

  18. Severe iatrogenic bradycardia related to the combined use of beta-blocking agents and sodium channel blockers

    Directory of Open Access Journals (Sweden)

    Kawabata M

    2015-02-01

    Full Text Available Mihoko Kawabata,1 Yasuhiro Yokoyama,1 Takeshi Sasaki,1 Susumu Tao,1 Kensuke Ihara,1 Yasuhiro Shirai,1 Tetsuo Sasano,2 Masahiko Goya,1 Tetsushi Furukawa,3 Mitsuaki Isobe,4 Kenzo Hirao1 1Heart Rhythm Center, Tokyo Medical and Dental University, Tokyo, Japan; 2Department of Biofunctional Informatics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 3Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; 4Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan Purpose: Drug-induced bradycardia is common during antiarrhythmic therapy; the major culprits are beta-blockers. However, whether other antiarrhythmic drugs are also a significant cause of this, alone or in combination with beta-blockers, is not well known. Methods: We retrospectively investigated the records of all patients hospitalized at our institution for drug-related bradycardia from the years 2004 to 2012. Patients with cardiac disease and electrolytic or hormonal abnormalities that could cause bradyarrhythmias were excluded. Results: Eight patients were identified (mean age, 79±5 years; range, 71–85 years; 6 women. Three patients were taking only beta-blockers (hereafter referred to as the BB group, while five patients were on both beta-blockers and Na channel blockers (hereafter referred to as the BB + Na group. Heart rates ranged from 20~49 beats/minute on arrival. The initial electrocardiogram showed sinus bradycardia (n=6 or sinus arrest with escape beats (n=2. QRS duration was 80–100 ms. The clinical presentation of the BB + Na group was considerably worse than that of the BB group, and included cardiogenic shock and heart failure. Four of the BB + Na patients had been on their medications for over 300 days. The BB group recovered solely with drug discontinuation, while 4 of the 5 patients in the BB + Na group needed additional

  19. Oral care.

    Science.gov (United States)

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. Copyright © 2011 S. Karger AG, Basel.