WorldWideScience

Sample records for oral agent combination

  1. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

    Science.gov (United States)

    Kim, Jeong S; Jang, Sun W; Son, Miwon; Kim, Byoung M; Kang, Myung J

    2016-01-20

    The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (pIP6-containing ECT were approximately 7.9- (pIP6 for an oral therapy with the bisphosphonate for improved BA. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. 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.

  3. Combining insulins with oral antidiabetic agents: effect on hyperglycemic control, markers of cardiovascular risk and disease

    Directory of Open Access Journals (Sweden)

    Kjeld Hermansen

    2008-06-01

    Full Text Available Kjeld Hermansen, Lene Sundahl Mortensen, Marie-Louise HermansenDepartment of Endocrinology and Metabolism C, Aarhus University Hospital, DK-8000 Aarhus, DenmarkAbstract: Patients with type 2 diabetes mellitus (T2DM have an increased risk of cardiovascular disease (CVD. Unfortunately, several potential barriers exist for CVD risk management in diabetes, including the need for significant lifestyle changes, potential problems with hypoglycemia, weight gain, injection tolerability, treatment complexity with current diabetes therapies and other, unmodifiable factors. Improving glycemic control may impact CVD risk. Treatment of T2DM usually starts with lifestyle changes such as diet and exercise. When these become insufficient, pharmacotherapy is required. Various oral antidiabetic drugs (OADs are available that reduce hyperglycemia. The first line of therapy is usually metformin, since it does not increase weight and seems to have a beneficial effect on CVD mortality and risk factors. As T2DM progresses, insulin treatment becomes necessary for the majority of patients. The last few years have seen the development of long-acting, rapid-acting, and premixed insulin analog formulations. The treat-to-target algorithms of recent studies combining OADs plus insulin analogs have demonstrated that patients can reach glycemic treatment targets with low risk of hypoglycemia, greater convenience, and – with some analogs – limited weight gain vs conventional insulins. These factors may possibly have a positive influence on CVD risk. Future studies will hopefully elucidate the benefits of this approach.Keywords: diabetes mellitus, type 2 diabetes, cardiovascular disease, hyperglycemia, insulin, oral antidiabetic drugs

  4. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, together with bevacizumab, cetuximab, or panitumumab on human colorectal cancer xenografts

    OpenAIRE

    Tsukihara, Hiroshi; NAKAGAWA, FUMIO; SAKAMOTO, KAZUKI; Ishida, Keiji; TANAKA, NOZOMU; OKABE, HIROYUKI; Uchida, Junji; Matsuo, Kenichi; Takechi, Teiji

    2015-01-01

    TAS-102 is a novel oral nucleoside antitumor agent that consists of trifluridine (FTD) and tipiracil hydrochloride (TPI) at a molecular ratio of 1:0.5, and was approved in Japan in March 2014 for the treatment of patients with unresectable advanced or recurrent colorectal cancer that is refractory to standard therapies. In the present study, we used colorectal cancer xenografts to assess whether the efficacy of TAS-102 could be improved by combining it with bevacizumab, cetuximab or panitumum...

  5. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, together with bevacizumab, cetuximab, or panitumumab on human colorectal cancer xenografts.

    Science.gov (United States)

    Tsukihara, Hiroshi; Nakagawa, Fumio; Sakamoto, Kazuki; Ishida, Keiji; Tanaka, Nozomu; Okabe, Hiroyuki; Uchida, Junji; Matsuo, Kenichi; Takechi, Teiji

    2015-05-01

    TAS-102 is a novel oral nucleoside antitumor agent that consists of trifluridine (FTD) and tipiracil hydrochloride (TPI) at a molecular ratio of 1:0.5, and was approved in Japan in March 2014 for the treatment of patients with unresectable advanced or recurrent colorectal cancer that is refractory to standard therapies. In the present study, we used colorectal cancer xenografts to assess whether the efficacy of TAS-102 could be improved by combining it with bevacizumab, cetuximab or panitumumab. TAS-102 was orally administered twice a day from day 1 to 14, and bevacizumab, cetuximab and panitumumab were administered intraperitoneally twice a week for 2 weeks. Growth inhibitory activity was evaluated based on the relative tumor volume (RTV) after 2 weeks of drug administration and time taken for the relative tumor volume to increase five-fold (RTV5). Tumor growth inhibition and RTV5 with TAS-102 and bevacizumab combination treatment were significantly better than those with TAS-102 or bevacizumab alone in the SW48 and HCT116 tumor models, and the concentration of phosphorylated FTD in tumors determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was higher in the TAS-102 and bevacizumab combination group than in the TAS-102 monotherapy group. The combination of TAS-102 and cetuximab or panitumumab was also significantly more effective than either monotherapy in the SW48 tumor model. There was no significant difference in the body weight between the mice treated with TAS-102 monotherapy and any of the combination therapies on day 29. Our preclinical findings indicate that the combination therapy of TAS-102, bevacizumab and cetuximab or panitumumab is a promising treatment option for colorectal cancer.

  6. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, with irinotecan hydrochloride on human colorectal and gastric cancer xenografts.

    Science.gov (United States)

    Nukatsuka, Mamoru; Nakagawa, Fumio; Saito, Hitoshi; Sakata, Minoru; Uchida, Junji; Takechi, Teiji

    2015-03-01

    TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5. TAS-102 was approved in Japan in March 2014 for the treatment of patients with unresectable, advanced or recurrent colorectal cancer that is refractory to standard therapies. In the present study, enhancement of the therapeutic efficacy using a combination therapy of TAS-102 and irinotecan hydrochloride (CPT-11) was evaluated in a colorectal and gastric cancer xenograft-bearing nude mouse model. TAS-102 was orally administered twice a day from day 1 to 14, and CPT-11 was administered intravenously on days 1 and 8. The growth-inhibitory activity was evaluated based on the tumor volume and the growth-delay period, which was estimated based on the period required to reach a tumor volume that was five-times greater than the initial volume (RTV5). The tumor growth-inhibitory activity and the RTV5 of the group receiving TAS-102 with CPT-11 were significantly superior to those of both agents as monotherapy for mice with KM12C, KM12C/5-FU, DLD-1/5-FU, and SC-2 xenografts (p<0.01). No significant decrease in body weight was observed. The present pre-clinical findings indicated that the combination of TAS-102 and CPT-11 is a promising treatment option for colorectal or gastric cancer, not only for chemo-naïve tumors, but also for recurrent tumors after 5-fluorouracil (5-FU)-based chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Efficacy of Combination Chemotherapy Using a Novel Oral Chemotherapeutic Agent, TAS-102, with Oxaliplatin on Human Colorectal and Gastric Cancer Xenografts.

    Science.gov (United States)

    Nukatsuka, Mamoru; Nakagawa, Fumio; Takechi, Teiji

    2015-09-01

    TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine (FTD) and the thymidine phosphorylase inhibitor tipiracil hydrochloride (at a molar ratio of 1:0.5) that was approved in Japan in 2014 for the treatment of unresectable advanced or recurrent colorectal cancer. In the present study, the enhancement of therapeutic efficacy using a combination of TAS-102 and oxaliplatin was evaluated in a xenograft-bearing nude mouse model of colorectal and gastric cancer. TAS-102 was orally administered twice-a-day from day 1 to 14, and oxaliplatin was administered intravenously on days 1 and 8. The in vivo growth-inhibitory activity was evaluated based on the tumor volume and the growth-delay period, was estimated based on the period required to reach a tumor volume five-times greater than the initial volume (RTV5). The tumor growth-inhibitory activity and RTV5 in mice administered TAS-102 with oxaliplatin were significantly superior to those associated with either monotherapy in mice with colorectal (HCT 116, SW-48; p<0.001) and gastric cancer (SC-2, MKN74; p<0.001). MKN74/5FU, a 5-fluorouracil-resistant MKN74 sub-line, was sensitive to both FTD and oxaliplatin in vitro. In vivo, TAS-102 alone was effective in MKN74/5FU, and its anti-tumor activity was significantly enhanced in combination with oxaliplatin (p<0.001). No significant decrease in body weight or toxicity was observed compared to either monotherapy. The present pre-clinical findings indicate that combination of TAS-102 and oxaliplatin is a promising treatment option for colorectal or gastric cancer, and can be utilized in both chemo-naïve tumors and recurrent tumors after 5-fluorouracil treatment. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. The relevance of the pharmacologic properties of a progestational agent to its clinical effects as a combination oral contraceptive.

    OpenAIRE

    Upton, G. V.; Corbin, A

    1989-01-01

    Levonorgestrel (LNg) is known for its marked progestational/contraceptive activity. As shown in animal experiments, however, high doses of LNg are required to elicit an androgenic response; in contrast, considerably lower doses of LNg are required for antiovulatory (contraceptive) action. Thus, a large dose separation exists between androgenic and contraceptive activity. When LNg is combined with an estrogen, as in the contraceptive formulations, the androgenic response is attenuated or negat...

  9. Safety of an oral anticancer agent (trifluridine/tipiracil combination tablet) in patients with advanced and recurrent colorectal cancer.

    Science.gov (United States)

    Kimura, M; Go, M; Iwai, M; Ito, D; Asano, H; Usami, E; Teramachi, H; Yoshimura, T

    2016-04-01

    We retrospectively studied the safety of trifluridine/tipiracil combination tablet (TAS-102) monotherapy in patients with advanced and recurrent colorectal cancer. Adverse events to TAS-102 monotherapy were observed in 22 out of 23 cases (95.7%). The most frequent adverse events were neutropenia (69.6%), nausea (53.2%), and malaise (30.4%). Treatment was postponed in 54 (59.3%) out of 91 courses, and in 34 (66.7%) of these 54 courses, the delay in treatment was due to bone marrow suppression. Seven patients with peritoneal metastases suffered from nausea, whilst none of the patients without peritoneal metastases had nausea (p = 0.0139). Nausea and vomiting during a previous chemotherapy cycle was significantly associated with nausea after TAS-102 treatment (p = 0.0007), and the treatment cycles were significantly longer in patients with grade 3 or 4 neutropenia (p = 0.0061). Our results suggest that the incidence of nausea was higher in patients treated with TAS-102. Therefore, it is important to inform patients of the risk of these toxicities and to provide enhanced supportive care. Moreover, we recommend that, for patients with repeated treatment postponement due to neutropenia, the dosage should be fixed based on therapeutic efficacy and prognosis.

  10. 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 univer......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...... compared to women treated with sulphonylurea or insulin (32 vs. 7 vs. 10%, P neonatal morbidity was observed between the orally treated and insulin-treated group; no cases of severe hypoglycaemia or jaundice were seen in the orally treated groups. However, in the group of women...

  11. [Antilipemic agents in combined therapy].

    Science.gov (United States)

    Márk, László; Császár, Albert

    2002-08-25

    In the prevention of coronary heart disease the aim to achieve the target cholesterol and triglyceride levels and the maximal risk reduction leads to the combination of lipid lowering agents. The importance of the combination is supported by the fact that in monotherapy use of the high dose of the drugs, the lipid lowering effect is modest and the side effects are more frequent. The combined therapy is expected to be used more frequently despite the fact, that the improperly applied combination could have serious unfavourable effects. The authors review the advantages and drawbacks of the fibrate-statin combination, which could be used in the most frequent lipid abnormality, the high cholesterol and high triglyceride level, when the combination of micronized fenofibrate and fluvastatin is recommended. Beside the co-administration of other lipid lowering drugs (nicotine acid and resins), it is discussed the combination of statins and fibrates with a new, cholesterol absorption inhibitor, ezetimibe, a well tolerated drug with advantageous safety profile. Considering further metabolic risks the combination of lipid lowering drugs with glitazones, hormone replacement therapy, homocysteine reducing agents is as well highlighted.

  12. 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...

  13. Effect of a novel oral chemotherapeutic agent containing a combination of trifluridine, tipiracil and the novel triple angiokinase inhibitor nintedanib, on human colorectal cancer xenografts.

    Science.gov (United States)

    Suzuki, Norihiko; Nakagawa, Fumio; Matsuoka, Kazuaki; Takechi, Teiji

    2016-12-01

    Trifluridine/tipiracil (TFTD) is a combination drug that is used for the treatment of metastatic colorectal cancer and was formerly known as TAS-102. It is a combination of two active pharmaceutical compounds, trifluridine, an antineoplastic thymidine-based nucleoside analog, and tipiracil, which enhances the bioavailability of trifluridine in vivo. TFTD is used for the treatment of patients with unresectable advanced or recurrent colorectal cancer that is resistant to standard therapies. In the present study, the anticancer effects of trifluridine in combination with nintedanib, an oral triple angiokinase inhibitor, on human colorectal cancer cell lines were investigated. The cytotoxicity against DLD-1, HT-29, and HCT116 cell lines was determined by the crystal violet staining method. The combination of trifluridine and nintedanib exerted an additive effect on the growth inhibition of DLD-1 and HT-29 cells and a sub-additive effect on HCT116 cells, as determined by isobologram analyses. Subsequently, the human colorectal cancer cell lines were implanted subcutaneously into nude mice to allow the evaluation of the in vivo tumor growth inhibitory effects of TFTD and nintedanib combination therapy. TFTD (150 mg/kg/day) and/or nintedanib (40 mg/kg/day) were orally administered to the mice twice daily from day 1 to day 14. The tumor growth inhibition with combination therapy was 61.5, 72.8, 67.6 and 67.5% for the DLD-1, DLD-1/5-FU, HT-29, and HCT116 xenografts, respectively. This was significantly (P<0.05) higher than the effects of monotherapy with either TFTD or nintedanib. These results demonstrated the effectiveness of the combination of TFTD and nintedanib in the treatment of colorectal cancer xenografts. The concentration of trifluridine incorporated into DNA in the HT-29 and HCT116 tumors was determined by liquid chromatography-tandem mass spectrometry. The incorporation levels following treatment with TFTD and nintedanib for 14 consecutive days were

  14. Monitoring anticoagulant therapy with new oral agents

    Science.gov (United States)

    Ramos-Esquivel, Allan

    2015-01-01

    Thromboembolic disease is a major leading cause of mortality and morbidity in industrialized countries. Currently, the management of these patients is challenging due to the availability of new drugs with proven efficacy and security compared to traditional oral vitamin K antagonists. These compounds are characterized by a predictable pharmacokinetic profile for which blood monitoring is not routinely needed. Nevertheless, some data have suggested inter-patient variability in the anticoagulant effect of these drugs, raising concerns about their effectiveness and safety. Although mass-spectrometry is the gold standard to determine drug plasma concentrations, this method is not widely available in every-day practice and some coagulation assays are commonly used to determine the anticoagulant effect of these drugs. The present review aims to summarize the current knowledge regarding the clinical question of how and when to monitor patients with new anticoagulant oral agents. PMID:26713281

  15. 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.

  16. Effect of a novel oral chemotherapeutic agent containing a combination of trifluridine, tipiracil and the novel triple angiokinase inhibitor nintedanib, on human colorectal cancer xenografts

    OpenAIRE

    SUZUKI, Norihiko; NAKAGAWA, FUMIO; Matsuoka, Kazuaki; Takechi, Teiji

    2016-01-01

    Trifluridine/tipiracil (TFTD) is a combination drug that is used for the treatment of metastatic colorectal cancer and was formerly known as TAS-102. It is a combination of two active pharmaceutical compounds, trifluridine, an antineoplastic thymidine-based nucleoside analog, and tipiracil, which enhances the bioavailability of trifluridine in vivo. TFTD is used for the treatment of patients with unresectable advanced or recurrent colorectal cancer that is resistant to standard therapies. In ...

  17. Assessment and measurement of adherence to oral antineoplastic agents.

    Science.gov (United States)

    Spoelstra, Sandra L; Given, Charles W

    2011-05-01

    The increase in oral anticancer medications with complex regimens creates a need to assure that patients are taking therapeutic dosages as prescribed. This article reviews the assessment and measurement of adherence to oral antineoplastic agents. Research and journal articles from CINAHL and PubMed. Assessing and measuring adherence to oral antineoplastics should include three dimensions: the percentage of medications taken, the duration, and the timing of taking the medication. Clinicians need to conduct ongoing assessment and measurement of adherence to oral antineoplastic agents. This includes eliciting patient report of adherence, pill counts, drug diaries, and pharmacy or medical record audits. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. 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

    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 with the comb......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...... with the combination of the two over 5-7 years of follow-up. We also assessed comparative safety. METHODS: In a multicentre, open-label trial, 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A(1c) (HbA(1c)) of 7.9% were randomly assigned to addition of rosiglitazone (n...... were increased mainly in women randomly assigned to rosiglitazone. Mean HbA(1c) was lower in the rosiglitazone group than in the control group at 5 years. INTERPRETATION: Addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes is confirmed to increase the risk of heart...

  19. Oral Antineoplastic Agents: Assessing the Delay in Care

    OpenAIRE

    2015-01-01

    The study was undertaken to determine the length of time between when a prescription for an oral antineoplastic agent is written by the provider and when the medication is received by the patient and to identify risk factors that significantly increase time to medication receipt. First-time fill prescriptions for oral antineoplastic agents were identified. The date the prescription was written and received by the patient was determined. A retrospective review was completed to gather additiona...

  20. Gestational diabetes mellitus management with oral hypoglycemic agents.

    Science.gov (United States)

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

    2014-12-01

    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.

  1. Choosing a combined oral contraceptive pill

    OpenAIRE

    2015-01-01

    The combined oral contraceptive pill is an effective contraceptive method which can also offer other benefits. However, other contraceptive options should be discussed. If the pill is the chosen method, prescribe a pill with the lowest effective dose of oestrogen and progestogen.

  2. [Progress in study of oral biofilm dispersal-inducing agents].

    Science.gov (United States)

    Yan, Zhu; Jingmei, Yang; Dingyu, Duan; Yi, Xu

    2014-12-01

    Communities of bacteria wrapped in self-generated extracellular polymeric matrix and attached to a solid surface are known as biofilm. Biofilm formation and development can be divided into three stages: adhesion of cells to a surface, reproduction of the cells, and dispersion of cells. The procedure, which surface-attached biofilm disperses bacterial cells into the environment to colonize new sites, is defined as biofilm dispersal. Biofilm dispersal is an essential stage of biofilm life cycle. It plays an important role in the transmission of bacteria. For many pathogenic bacteria, biofilm dispersal can transform bacteria in biofilm into planktonic state and promote the spread of infection. The formation of biofilm may increase the resistance of bacteria to antimicrobial agent and host defence response compared with planktonic cells. In the oral cavity, oral microorganism can attach to the surface of oral tissue and prosthesis to form biofilm. Dental caries and periodontal disease are oral chronic infections diseases of the oral tissue. The occurrence of them has a close relationship with biofilm. The mechanism of dispersal is a hot topic in recent years. Some agents which promote dispersal might be a therapeutic potential against biofilm infections. The clinical implication of dispersal agents and potential application are promising. This article reviews the dispersal-inducing agents of oral biofilms.

  3. Therapeutic options for herpes labialis, I: Oral agents.

    Science.gov (United States)

    Elish, Diana; Singh, Fiza; Weinberg, Jeffrey M

    2004-07-01

    Given the prevalence of herpes labialis, effective therapy has the potential to affect the lives of many and presents a challenge for clinicians. Over the last several years, most of the focus of herpes research has been on the treatment of genital herpes. Recently, however, several studies have been published examining the efficacy of therapies specifically for herpes labialis. Several therapeutic agents, both prescription and over-the-counter, are available for controlling and managing the disease. In this series of articles, we review oral and topical therapeutic agents that are available in the treatment of herpes labialis and its associated symptoms. This article will review oral treatment options.

  4. Garcinia xanthones as orally active antitumor agents.

    Science.gov (United States)

    Zhang, Xiaojin; Li, Xiang; Sun, Haopeng; Wang, Xiaojian; Zhao, Li; Gao, Yuan; Liu, Xiaorong; Zhang, Shenglie; Wang, Yanyan; Yang, Yingrui; Zeng, Su; Guo, Qinglong; You, Qidong

    2013-01-10

    Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D₇.₄, aqueous solubility, and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.

  5. Oral Antineoplastic Agents: Assessing the Delay in Care

    Directory of Open Access Journals (Sweden)

    Brandi Anders

    2015-01-01

    Full Text Available The study was undertaken to determine the length of time between when a prescription for an oral antineoplastic agent is written by the provider and when the medication is received by the patient and to identify risk factors that significantly increase time to medication receipt. First-time fill prescriptions for oral antineoplastic agents were identified. The date the prescription was written and received by the patient was determined. A retrospective review was completed to gather additional information, including prescribed medication, indication, insurance coverage, patient assistance program use, dispensing pharmacy, and prior authorization requirements. The data was analyzed through multivariate statistical analysis and used to identify risk factors that may significantly increase the time to medication receipt. A total of 58 patients were included in the study. A median of 8 days elapsed between when the medication was prescribed and when it was received by the patient. Medication prescribed, absence of a Risk Evaluation Mitigation Strategies (REMS program, and insurance type are factors that increased time to medication receipt. An understanding of the median time involved, as well as factors affecting the time to delivery of prescriptions, will help healthcare providers better plan and prepare for the use of oral antineoplastic agents.

  6. Oral Antineoplastic Agents: Assessing the Delay in Care.

    Science.gov (United States)

    Anders, Brandi; Shillingburg, Alexandra; Newton, Michael

    2015-01-01

    The study was undertaken to determine the length of time between when a prescription for an oral antineoplastic agent is written by the provider and when the medication is received by the patient and to identify risk factors that significantly increase time to medication receipt. First-time fill prescriptions for oral antineoplastic agents were identified. The date the prescription was written and received by the patient was determined. A retrospective review was completed to gather additional information, including prescribed medication, indication, insurance coverage, patient assistance program use, dispensing pharmacy, and prior authorization requirements. The data was analyzed through multivariate statistical analysis and used to identify risk factors that may significantly increase the time to medication receipt. A total of 58 patients were included in the study. A median of 8 days elapsed between when the medication was prescribed and when it was received by the patient. Medication prescribed, absence of a Risk Evaluation Mitigation Strategies (REMS) program, and insurance type are factors that increased time to medication receipt. An understanding of the median time involved, as well as factors affecting the time to delivery of prescriptions, will help healthcare providers better plan and prepare for the use of oral antineoplastic agents.

  7. The effect of combined bleaching techniques on oral microbiota

    Directory of Open Access Journals (Sweden)

    Franz-Montan Michelle

    2009-01-01

    Full Text Available Aims : To evaluate the antimicrobial activity of 10% and 37% carbamide peroxide during dental bleaching in three different modes. Materials and Methods : This five-week double-blind randomized controlled trial included 32 volunteers assigned to four groups (n = 8. Each group received bleaching agents or placebo as an in-office and at-home treatment. The dental bleaching techniques were: In-office bleaching (37% carbamide peroxide: CP37; at-home bleaching (10% carbamide peroxide: CP10 and the association of both (CP37 and CP10. Saliva samples were collected right before (baseline, right after, 12 hours after, and seven days after the treatment. Counts of total microorganisms, Streptococci, and Mutans streptococci were carried out. Friedman test (α = 0.05 was used to compare the microorganism counts. Results : The number of the all oral microorganisms remained stable during all experiment. Conclusions : No bleaching agent (CP37, CP10 or the combination of both was able to reduce the oral microorganisms tested.

  8. Combination of tocolytic agents for inhibiting preterm labour.

    Science.gov (United States)

    Vogel, Joshua P; Nardin, Juan Manuel; Dowswell, Therese; West, Helen M; Oladapo, Olufemi T

    2014-07-11

    Preterm birth represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. Tocolytic agents include a wide range of drugs that can inhibit labour to prolong pregnancy. This may gain time to allow the fetus to mature further before being born, permit antenatal corticosteroid administration for lung maturation, and allow time for intra-uterine transfer to a hospital with neonatal intensive care facilities. However, some tocolytic drugs are associated with severe side effects. Combinations of tocolytic drugs may be more effective over single tocolytic agents or no intervention, without adversely affecting the mother or neonate. To assess the effects on maternal, fetal and neonatal outcomes of any combination of tocolytic drugs for the treatment of preterm labour when compared with any other treatment, no treatment or placebo. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014) and reference lists of retrieved studies. We included randomised controlled trials comparing a combination of tocolytic agents, administered by any route or any dose, for inhibiting preterm labour versus any other treatment (including other combinations of tocolytics or single tocolytics), no intervention or placebo. Two review authors independently assessed study reports for eligibility, carried out data extraction and assessed risk of bias. Eleven studies met our inclusion criteria. Two studies did not report any outcome data relevant to the review, so the results of the review are based on nine trials that contributed data. Primary outcomes were perinatal mortality, serious maternal or infant outcomes, adverse drug reactions, birth before 48 hours of trial entry, birth before 34 weeks' gestation and preterm neonates delivered without a full course of antenatal steroids completed 24 hours before birth. The quality of evidence in included trials was mixed; only three of the trials were

  9. Combined oral contraceptives: health benefits beyond contraception.

    Science.gov (United States)

    Caserta, D; Ralli, E; Matteucci, E; Bordi, G; Mallozzi, M; Moscarini, M

    2014-09-01

    It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.

  10. Insulin versus oral agents in the management of Cystic Fibrosis Related Diabetes: a case based study

    Directory of Open Access Journals (Sweden)

    Langdon Leora J

    2006-06-01

    Full Text Available Abstract Background Insulin is the recommend therapeutic agent of choice for the management of Cystic Fibrosis Related Diabetes (CFRD, despite only sub-optimal reductions in glycemic control and increased morbidity and mortality reported by centers using this agent. The newer insulin sensitizing agents demonstrated to have anti-inflammatory mechanisms may provide an alternative management option for CFRD. Methods A prospective case based therapeutic comparison between insulin, sulfonylurea, metformin and thiazolidinedione was observed over one decade with 20 CFRD patients diagnosed using American Diabetes Association guideline standards. Patients entering the study elected treatment based on risk and benefit information provided for treatment options. Patients receiving organ transplant or requiring combination diabetic medications were excluded from the study. Results No statistical advantage was achieved regarding overall glycemic control for oral agents over insulin. Additional outcome measures including changes in weight, liver function testing and FEV1 were not statistically significant. Conclusion Insulin alone may not be the only therapeutic option in managing CFRD. Oral hypoglycemic agents were equally effective in treating CFRD and may provide an alternative class of agents for patients reluctant in using insulin.

  11. 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

    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...... with an analysis of combinations of two SNP genotypes from among the 325 SNPs. Two clusters of combinations containing 95 patient specific combinations were significantly associated with oral cancer or leukoplakia. Of 373 patients with oral cancer 205 patients had a number of these 95 combinations in their genome...

  12. 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...

  13. Review of atrial fibrillation outcome trials of oral anticoagulant and antiplatelet agents.

    Science.gov (United States)

    Bassand, Jean-Pierre

    2012-03-01

    Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplatelet-vitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk.

  14. 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.

  15. Cost variation analysis of Oral Hypoglycaemic agents available in Indian market: An Economic Perspective

    Directory of Open Access Journals (Sweden)

    Salman Hussain

    2015-05-01

    Full Text Available Introduction: Diabetes, a chronic disorder and requires life-long treatment. Cost of drug treatment is a major hurdle related to medication compliance in Type2 Diabetes Mellitus. Objective: To compare the cost and percentage price variation of single and combination therapy of oral hypoglycaemic agents across the different brands available in the Indian market. Methods: India’s medical research body, particularly Indian Council of Medical Research (ICMR issue guidelines for the management of T2DM. ICMR guidelines were perused to understand the management of T2DM. Current Index of Medical Specialities (CIMS Oct.-Jan.2015 edition and Indian Drug Review (IDR Issue 1, Jan.2015 were used to capture the price of oral hypoglycaemic agents across the different brands available in the Indian market. Percentage price variations between minimum and maximum cost of drugs were computed. Results: In the single drug therapy sulfonylurea group of drugs like Glipizide 5mg shows maximum variation of 780% followed by Glimepiride 2mg formulation by 682%, while the non-sulfonylurea groups of drug say, Pioglitazone 15mg shows maximum variation of 600%. In combination therapy Glimepiride 1mg + Metformin 500mg shows maximum price variation of 533%. Positive correlation exists between the number of manufacturing companies and percentage price variation of drugs. Conclusion: There is wide variation exist between the minimum and maximum cost among single as well as combination therapy of oral hypoglycaemic agents. A maximum of 9 & 6 fold price variation was reported in single and combination therapy respectively.

  16. Long-term safety and efficacy of linagliptin as monotherapy or in combination with other oral glucose-lowering agents in 2121 subjects with type 2 diabetes: up to 2 years exposure in 24-week phase III trials followed by a 78-week open-label extension.

    Science.gov (United States)

    Gomis, R; Owens, D R; Taskinen, M-R; Del Prato, S; Patel, S; Pivovarova, A; Schlosser, A; Woerle, H-J

    2012-08-01

    Aim:  The aim of this study was to evaluate the long-term safety, tolerability and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin given either alone or in combination with other oral glucose-lowering agents in persons with type 2 diabetes. Methods:  A 78-week open-label extension study evaluated subjects who participated in one of four preceding 24-week, randomised, double-blind, placebo-controlled parent trials and who received linagliptin, linagliptin + metformin, linagliptin + metformin + a sulphonylurea or linagliptin + pioglitazone (all with linagliptin administered orally once daily). Individuals receiving one of these treatments during a previous trial continued the same treatment (n = 1532) for up to a total of 102 weeks, whereas those previously receiving placebo were switched to linagliptin (n = 589). All 2121 participants received at least one dose of the trial medication and were included in the primary safety analysis. Results:  In subjects previously receiving active treatment, the glycosylated haemoglobin A(1c) reduction achieved during the 24-week parent trials was sustained through the 78-week extension period (change from baseline to week 102: -0.8%). Drug-related adverse events were experienced by 14.3% of participants. Hypoglycaemia occurred in 13.9% of participants and was similar between those previously receiving treatment (13.6%) and those switching from placebo to linagliptin (14.6%). Hypoglycaemia occurred most frequently with the use of metformin + a sulphonylurea background therapy (11%). Overall, no clinically relevant changes in body weight were observed. Conclusion:  Long-term treatment with linagliptin was well tolerated with no change in the safety profile observed during the extension study. Sustained long-term glycaemic control was maintained for up to 102 weeks with either linagliptin monotherapy or linagliptin in combination with other oral glucose-lowering agents. © 2012

  17. The observation of curative effect of combined with insulin therapy after failure treatment with oral hypoglycemic agents for type 2 diabetes%口服降糖药治疗2型糖尿病失效联合甘精胰岛素治疗疗效观察

    Institute of Scientific and Technical Information of China (English)

    熊东林

    2013-01-01

    目的:观察口服降糖药治疗2型糖尿病失效后,联合甘精胰岛素治疗糖尿病的疗效。方法筛选68例单用口服降糖药血糖控制不理想的2型糖尿病患者,睡前(2130)加用甘精胰岛素(来得时),治疗14周,比较前后空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、空腹C肽、餐后2hC肽、体重变化及低血糖的发生。结果加用甘精胰岛素组治疗14周后,患者FPG、2hPG、HbA1c较治疗前明显下降(P<0.01),餐后2hC肽较治疗前明显升高(P<0.01),未见低血糖发生,体重指数影响不大。结论对单用口服药效果不佳的2型糖尿病,需及时加用甘精胰岛素治疗。%Objective To observe the curative effect of combined with insulin therapy after failure treatment with oral hypoglycemic agents for type 2 diabetes. Method Screening 68 cases with oral hypoglycemic agents alone with no ideal blood sugar control in type 2 diabetes, patients bedtime(9 30 pm) plus insulin glargine(Lantus) treatment with 14 weeks treatment, compared before and after FPG, 2hPG, HbA1c, fasting C peptide, 2h postprandial C-peptide, weight changes and the occurrence of low blood sugar. Results Combined with insulin treatment after 14 weeks , patients’s FPG, 2hPG, HbA1c significantly decreased than that before treatment(P<0.01), and with postprandial 2h C-peptide significantly higher(P<0.01). Conclusion It should be timely combined with insulin after failure treatment with oral hypoglycemic agents alone for type 2 diabetes.

  18. Phototoxic reaction to a combined oral contraceptive (levonorgestrel/ethinylestradiol).

    Science.gov (United States)

    Richarz, N A; Aguilera, J; Castillo, G; Fuente, M J; Ferrándiz, C; Carrascosa, J M

    2017-09-13

    We present the case of a phototoxic skin reaction due to the regular intake of a combined oral contraceptive (levonorgestrel/ethinylestradiol). Upon spectrophotometer testing, we demonstrated high absorption in the UV-B region of the solar spectrum of the combined product (Ovoplex®), especially for the estrogen compound (ethinylestradiol).

  19. Safe handling and administration considerations of oral anticancer agents in the clinical and home setting.

    Science.gov (United States)

    Lester, Joanne

    2012-12-01

    The use of hormonal, chemotherapeutic, and targeted biologic oral agents has exponentially increased since the early 2000s. Oral therapies have the advantage of persistent exposure of the cytotoxic drug to tumor cells and the tumor environment. The use of oral anticancer agents provides therapeutic drug treatment for patients with cancer in the comfort of their home or alternative settings, such as retirement homes and assisted living or extended-care facilities. Practices to ensure safe storage, handling, administration, and disposal of oral agents are necessary to prevent additional exposure of hazardous substances to the environment, professionals, patients, family members, and caretakers. Providers should consider potential barriers to adherence and compliance, and develop strategies to ensure optimal therapeutic benefit prior to initiation of oral agents.

  20. 1294张口服降糖药处方分析%Analysis of 1294 prescriptions of oral hypoglycemic agents

    Institute of Scientific and Technical Information of China (English)

    谢雅君; 吴久鸿; 王杰松; 薛克昌; 许樟荣

    2011-01-01

    Objective: To investigate the utilization of oral hypoglycemic agents in outpatient in our hospital and provide reference for clinical medication. Methods: The prescriptions of oral hypoglycemic agents in outpatient in January 2010 were retrospectively analyzed, in respect of the numbers of prescriptions, recipe quantity and drug combination. The DDDs and DUI were analyzed. Results: Oral hypoglycemic agents used with high frequency were biguanide (54.87%), sulfonylurea (34.47%) and α -glycosidase inhibitor (34.47%). Metformin and acarbose were used most. The DUI of 16 drugs was close to 1 among 20 oral hypoglycemic agents. The proportion of combined oral hypoglycemic agents accounted for 45.98% in all prescriptions. The most common combination use of oral hypoglycemic agents were biguanide and sulfonylurea, sulfonylurea and α -glycosidase inhibitor. Conclusion: The utilization of oral hypoglycemic agents in outpatient of our hospital was reasonable.%目的:了解我院门诊口服降糖药的使用情况,为临床用药提供参考.方法:回顾性分析我院门诊2010年1月份的口服降糖药处方,对处方数、处方量和联合用药等进行统计,并计算用药频度(DDDs)和药物利用指数(DUI).结果:使用频次较多的降糖药分别是双胍类(54.87%)、磺酰脲类(34.47%)和α-葡萄糖苷酶抑制剂(34.47%);格华止和拜唐苹是处方量最多的药物品种;20种口服降糖药中,有16种药物的DUI值接近1;口服降糖药联合应用占总处方数的45.98%,最常见为磺酰脲类+双胍类和磺酰脲类+α-葡萄糖苷酶抑制剂.结论:我院门诊使用降糖药物基本合理.

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

    OpenAIRE

    Maria Martinez; Dimitrios A. Tsakiris

    2015-01-01

    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 ...

  2. Management of oral Graft versus Host Disease with topical agents: A systematic review

    Science.gov (United States)

    Khan, Zahid; Poveda, Ana; Higham, Jonathan; Richards, Andrea; Monteiro, Luis; Jané-Salas, Enric; Lopez-Lopez, José; Warnakulasuriya, Saman

    2016-01-01

    Background Oral Graft-versus-Host Disease (oGvHD) is a common complication of haematopoietic stem cell transplantation. Choosing the right topical application to be used intra orally can be a challenge. Consequently, the aim of this work is to review the effectiveness and safety of topical agents currently used in the management of the inflammatory mucosal lesions encountered in oGVHD. Material and Methods We carried out electronic searches of publications up to May 2015 of the databases Pubmed, National Library of Medicine’s Medline, Embase and the Cochrane Central Register of Controlled Clinical trials to identify potentially relevant studies (keywords: “oral”, “graft”, “versus”, “host”, “disease” and “treatment”). The main inclusion criterion was the reported use of a topical agent which was not intentionally swallowed when used for the treatment of oGVHD. A 3-point grading system, described by the Swedish Council on Technology Assessment in Health Care and the Centre for Reviews and Dissemination, University of York, was used to rate the methodological quality of the papers. Results From the 902 entries identified in the search, 7 studies qualifying for inclusion were analysed. Overall, there is limited evidence with regards to the effectiveness of topical steroids for oGVHD. However, the studies showed some effect of Budesonide alone and when combined with dexamethasone. Topical tacrolimus also appears to have some effect and clobetasol propionate mouthwash had a significantly better clinical response than dexamethasone mouthwash in treating oGVHD. Conclusions As the number of clinical trials conducted is limited, there is little evidence to support the use of topical therapies to treat the inflammatory mucosal lesions found in oGVHD. High quality randomised control trials are needed in order to measure the effectiveness of any topical application for the treatment of the inflammatory mucosal lesions found in oGVHD. Key words:Oral

  3. Antitumor and anticytopenic effects of aqueous extracts of propolis in combination with chemotherapeutic agents.

    Science.gov (United States)

    Suzuki, Ikukatsu; Hayashi, Ikuo; Takaki, Takayuki; Groveman, Debra S; Fujimiya, Yoshiaki

    2002-10-01

    Using an ICR mouse model bearing a syngeneic Ehrlich ascitis carcinoma, the present study was undertaken to examine the effects of crude, water-soluble propolis (CWSP) on tumor progression, chemotherapeutic efficacy, and hematopoiesis in the peripheral blood. It was demonstrated that CWSP, administered subcutaneously, resulted in marked regression of tumor growth in mice, at the early phase after tumor inoculation (CWSP, p 0.05 vs. saline control). Peritoneal injection of CWSP into neonatal mice resulted in an increased lymphocyte/polymorphonuclear leukocyte ratio activity, indicating the potential activation of lymphoid cell lineages. These observations suggest that subcutaneously injected CWSP could regulate the development of tumors by possibly stimulating multicellular immunity. In addition, oral administration of CWSP concurrently with 5-fluorouracil (5-FU) or mitomycin C (MMC), significantly increased tumor regression as compared with the respective chemotherapy alone, illustrating the adjuvant effect of orally administered CWSP for tumor regression when combined with chemotherapeutic agents. To examine further the potential usefulness of CWSP for chemotherapeutic regimens, which induce profound multilineage hematopoietic suppression, mice that received CWSP orally in addition to a 5-FU or MMC were followed for absolute numbers of platelets and white and red blood cells. The oral administration of CWSP significantly ameliorated the cytopenia induced by 5-FU, resulting in recovery of white as well as red blood cell counts (5-FU plus CWSP, p red blood cells on day 25), but no marked effects on platelet counts was observed (5-FU plus CWSP, p > 0.05 vs. 5-FU alone or water control). On the other hand, CWSP significantly reduced all three MMC-induced cytopenias, especially at the later stage of the chemotherapeutic course (after day 30), suggesting repetitive requirements of oral administration of CWSP. In summary, subcutaneous administration of an aqueous CWSP

  4. 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.

  5. Therapeutic effects of insulin detemir combined with oral hypoglycemic agents on type 2 diabetic patients%口服降糖药联合地特胰岛素治疗2型糖尿病的临床疗效

    Institute of Scientific and Technical Information of China (English)

    宋晓敏; 王博; 蔡晓莺; 朱文

    2011-01-01

    Objective To investigate the clinical efficacy and safety of insulin detemir combined with oral hypoglycemic agents in treatment of type 2 diabetic patients. Methods 36 cases of type 2 diabetic patients treated with oral hypoglycemic agents were divided into NPH group(w=20) and insulin detemir group(n=16). The fasting blood glucose, glycated hemoglobin, lipids, blood pressure) body mass index were compared between pretreatment and posttreatment for 12 and 24 weeks. Hypoglycemia events were recorded. Results Fasting blood glucose and glycated hemoglobin were significantly decreased after treatment for 12, 24 weeks in both groups (p<0. 05). There were no significant differences in fasting blood glucose and glycated hemoglobin between the two groups after 12, 24 weeks of treatment. Hypoglycemic events were significanyly lower in insulin detemir group than in NPH group (P<0. 01). Weight gain was 0. 39kg in insulin detemir group and 0. 88kg in NPH group, there was no significant difference between two groups. Conclusion Insulin determir combined with oral hypoglycemic agents can effectively decrease blood glucose, with less incidence of hypoglycemia and less weight gain.%探讨在服用降糖药治疗的T2DM患者中,每天加用一次地特胰岛素治疗的临床疗效及安全性.单纯口服降糖药治疗、血糖控制不佳的T2DM患者36例,对照组在口服药基础上加用中效胰岛素,治疗组在其口服药基础上加用每日一次地特胰岛素,就寝前注射,比较治疗前、治疗后12周、24周空腹血糖、HbA1c、血脂、血压、BMI变化,记录低血糖发生率. 结果两组治疗后12、24周患者空腹血糖、HbA1c较治疗前均明显降低(P<0.05);治疗后12、24周两组间空腹血糖、HbA1c差异无统计学意义;地特胰岛素组低血糖发生率明显低于对照组(P<0.01);地特胰岛素组治疗24周后体重增加0.39kg,中效胰岛素组增加0.88kg,两组间差异无统计学意义. 结论 口服药

  6. The combined oral contraceptive pill -- recent developments, risks and benefits.

    Science.gov (United States)

    Dragoman, Monica V

    2014-08-01

    The introduction of the birth control pill as an effective, coitally-independent method of contraception was a public health milestone of the last century. Over time, combined oral contraception (COC) formulations and pill-taking regimens have evolved with improved safety and tolerability while maintaining contraceptive efficacy. In addition to protection against pregnancy, use of combined oral contraception confers a number of significant non-contraceptive benefits to users. COC use is also associated with well-studied risks. Common side effects are generally self-limiting and improve with increasing duration of use while serious adverse events, including venous thromboembolism, are rare among healthy COC users. Contraceptive decision-making should include consideration of both the risks and benefits of a given method versus the real consequences of unintended pregnancy.

  7. Mono- and combined antimicrobial agents efficiency in experimental wound infection

    Directory of Open Access Journals (Sweden)

    Наталія Ігорівна Філімонова

    2015-10-01

    Full Text Available Modern problems of antibiotic therapy are shown by wide range of side effects, both on organism and microbiological levels: the spread of allergies, toxic for organ systems reactions, dysbiosis development, and resistant pathogens formation and dissemination. Therefore the necessity of search for new effective drugs with significant antimicrobial activity applied for the wounds treatment arises. Development of combined remedies on the background of different origin antimicrobial agents’ derivatives is one of the fight directions against infectious diseases in the skin pathology. Recently among the existing antimicrobial agents one should focus on antiseptic drugs, due to degenerative and dysfunctional effect on microbial cell.Aim of research. The comparison of mono- and combined antimicrobial agents chemotherapeutic efficiency in the treatment of localized purulent infection under experimental conditions.Metods. The study of chemotherapeutic efficiency was carried out on the model of localized purulent Staphylococcus infection on albino mice weighting 14 – 16 g. S.aureus ATCC 25923 strains were used as infectious agents. The contamination was performed subcutaneously to the right side of mice’s skin after depilation. The animals were randomly divided into 4 groups: the 1st group – infected mice without treatment (control; the 2nd group – infected mice treated with a ciprofloxacin; the 3rd group – infected mice treated with a Ciprofloxacin and Decamethoxin combination; the 4th group – infected mice treated with a combined drug on the base of mutual prodrugs (Hexamethylenetetramine and Phenyl salicylate.Results. The efficiency of mono- and combined antimicrobial agents under experimental Staphylococcus wound infection conditions was studied. It was found that localized purulent staph center was formed more slowly in comparison with control and mono preparation use (2nd group of animals. The average index of skin lesions in comparison

  8. Adherence, compliance and persistence to oral antineoplastic therapy: a review focused on chemotherapeutic and biologic agents.

    Science.gov (United States)

    Gebbia, Vittorio; Bellavia, Giuseppe; Ferraù, Francesco; Valerio, Maria Rosaria

    2012-05-01

    To date, orally administered chemotherapy and biologic agents represent a significant percentage of all antineoplastic treatments in several types of cancer, which are most likely to increase in the near future. In this scenario, the issue of adherence and persistence to oral therapy is a key issue since poor compliance to oral antineoplastic treatments may negatively influence patients' clinical outcomes and, in turn, cause an increase in costs, number of hospitalizations and time spent in the hospital. The issue of adherence to new oral chemotherapeutic and/or biologic agents has not been deeply evaluated and data published in medical literature are quite scarce. Adherence is a multidimensional phenomenon, which may be influenced by patient- and health-care provider-related factors, anticancer therapy itself, education and socioeconomic aspects. Patients' selection plays, therefore, a key role in maximizing adherence and persistence to oral therapies. Treating health-care practitioners should first evaluate patient reliability to avoid prescribing oral treatments to patients with socioeconomic and medical conditions, which may predict poor adherence. Adherence and persistence to new oral biologic agents, which are linked to several side effects and whose use is constantly widening, should represent a main endpoint of clinical research in the nearest future.

  9. 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

  10. [Temozolomide, an oral chemotherapeutic agent with potential severe toxicity

    NARCIS (Netherlands)

    Soetekouw, P.M.M.B.; Gijtenbeek, J.M.M.; Maazen, R.W.M. van der; Kappelle, A.C.; Herpen, C.M.L. van

    2007-01-01

    Two patients, a 58-year-old man and a 55-year-old woman, both under treatment for glioblastoma multiforme, were admitted with fever and neutropenia a few weeks after starting to take the oncolytic agent temozolomide. The man died of a cerebral haemorrhage against a background of severe thrombocytope

  11. 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.

  12. Management of oral Graft versus Host Disease with topical agents: A systematic review

    OpenAIRE

    Albuquerque, Rui; Khan, Zahid; Poveda, Ana; Higham, Jonathan; Richards, Andrea; Monteiro,Luís Silva; Jane Salas, Enric; López López, José, 1958-; Warnakulasuriya, Saman

    2015-01-01

    Background Oral Graft-versus-Host Disease (oGvHD) is a common complication of haematopoietic stem cell transplantation. Choosing the right topical application to be used intra orally can be a challenge. Consequently, the aim of this work is to review the effectiveness and safety of topical agents currently used in the management of the inflammatory mucosal lesions encountered in oGVHD. Material and Methods We carried out electronic searches of publications up to May 2015 of the databases Pubm...

  13. The role of diet on the clinical pharmacology of oral antineoplastic agents.

    Science.gov (United States)

    Ruggiero, Antonio; Cefalo, Maria G; Coccia, Paola; Mastrangelo, Stefano; Maurizi, Palma; Riccardi, Riccardo

    2012-02-01

    The number of oral anticancer agents has greatly increased in recent years. It is a well-known fact that food intake can induce significant variations in the bioavailability of these drugs. The aim of this review is to describe the interactions between diet and oral anticancer drugs in terms of the possible effects of such interactions on reducing the antineoplastic activity of the drug or increasing its side effects. This was an analytical study of the numerous mechanisms leading to changes in the bioavailability of oral antineoplastic agents due to diet. Food-drug interactions can induce a delay, decrease or increase in the absorption of the oral chemotherapeutic agent. The concomitant intake of food and antineoplastic drugs influence the pharmacokinetic and pharmacodynamic drug processes depending on the composition of the food consumed and the specific interactions of the food with transport mechanisms (p-glycoprotein, multidrug resistance proteins) and intestinal enzymatic systems (cytochrome P450). In prescribing an oral anticancer agent, clinicians must consider the possibility that the consumption of specific food items has the potential to interfere with the pharmacokinetics and pharmacodynamics of the prescribed drug.

  14. Combination therapy with leflunomide and genetic engineering biological agents

    Directory of Open Access Journals (Sweden)

    Nataliya Vladimirovna Chichasova

    2011-06-01

    Full Text Available The paper gives data on the use of a combination of genetic engineering biological agents (GEBAs and leflunomide in patients with rheumatoid arthritis (RA. In accordance with the international guidelines, the majority of GEBAs should be given in a combination with methotrexate (MTX, which increases the efficacy of a number of GEBAs (tumor necrosis factor-α inhibitors, rituximab and affects tolerability (remikeid, humira. However, MTX cannot be always used in real practice. The data given in the paper on the efficiency and safety of the coadministration of leflunomide and a GEBA in patients with active RA, which are based on the results of randomized studies and national registers, including the Russian one, point to the compatibility of the results of treatment with this and GEBA-MTX combinations.

  15. 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

    Association of Supportive Care in Cancer/International Society for Oral Oncology. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation......, suggestion, and no guideline possible. RESULTS: A total of 49 papers across 15 interventions were examined. A new suggestion was developed in favor of systemic zinc supplements administered orally in the prevention of oral mucositis in oral cancer patients receiving radiation therapy or chemoradiation (Level......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...

  16. Female sexual dysfunction with combined oral contraceptive use.

    Science.gov (United States)

    Lee, Jean Jasmin M L; Tan, Thiam Chye; Ang, Seng Bin

    2017-06-01

    Combined oral contraceptive pills (COCs) remain one of the most popular forms of contraception to prevent unwanted pregnancy in women. While it is known that COCs can cause sexual dysfunction in women, there is currently no recommendation to screen for sexual function before and after initiation of COCs. We propose that, based on the evidence available, assessment of sexual function should be done at initiation of COCs, as well as at regular intervals thereafter. This would allow COC-related sexual dysfunction to be managed early, such as by switching the patient to newer-generation COCs or other forms of contraception. Copyright: © Singapore Medical Association.

  17. Oxidative Stress in Female Athletes Using Combined Oral Contraceptives

    OpenAIRE

    Cauci, S; Buligan, C; Marangone, M; Francescato, Mp.

    2016-01-01

    Background Oxidative stress in female athletes is understudied. We investigated oxidative stress in sportswomen of different disciplines according to combined oral contraceptive (OC) use and lifestyle/alimentary habits. Methods Italian sportswomen (n?=?144; mean age 23.4???4.2?years; body mass index 21.2???2.2?kg?m?2; sport activity 9.2???4.1?h?week?1) were analyzed; 48?% were volleyball players, 12.5?% soccer players, 10.4?% track-and-field sports, and followed by other disciplines? athletes...

  18. 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.

  19. Assessing the risk of birth defects associated with exposure to fixed-dose combined antituberculous agents during pregnancy in rats.

    Science.gov (United States)

    Awodele, O; Patrick, E B; Oluwatoyin Agbaje, Esther; Oremosu, A A; Gbotolorun, S C

    2012-01-01

    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 (P ≤ 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 (P ≤ 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 significantly

  20. 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

  1. Interactions between oral antineoplastic agents and concomitant medication: a systematic review.

    Science.gov (United States)

    Carcelero, Esther; Anglada, Helena; Tuset, Montse; Creus, Natalia

    2013-05-01

    In recent years, the number of oral antitumoral agents has considerably increased. Oral administration increases the risk of interactions, because most oral anticancer drugs are taken on a daily basis. Interactions can increase exposure to antitumoral agents or cause treatment failure. Many antitumoral drugs undergo enzymatic metabolism by cytochrome P450. As some act as inducers or inhibitors of one or more isoenzymes, they can lead to decreases or increases in plasma concentrations of concomitant drugs. Hence, cytostatic drugs can act not only as victims but also as perpetrators. P-glycoprotein, an efflux transporter, can also be involved in pharmacokinetic interactions. A Medline search was performed to summarize the available evidence of the most clinically relevant interactions between oral chemotherapy agents and other drugs. The search covered the period from 1966 until August 2012 for each antitumoral drug using the medical subject headings 'Drug Interactions' OR 'Pharmacokinetics'. While the present review is not exhaustive, it aims to increase clinicians' awareness of potential drug-drug interactions. As cancer patients are often polymedicated and treated by different physicians, the risk of drug interactions between antitumoral agents and other medications is high. More clinical interaction studies are encouraged to ensure appropriate antineoplastic pharmacokinetics in clinical practice.

  2. Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Nicolatou-Galitis, Ourania; Sarri, Triantafyllia; Bowen, Joanne; Di Palma, Mario; Kouloulias, Vassilios E.; Niscola, Pasquale; Riesenbeck, Dorothea; Stokman, Monique; Tissing, Wim; Yeoh, Eric; Elad, Sharon; Lalla, Rajesh V.

    2013-01-01

    Purpose The aim of this project was to review the available literature and define clinical practice guidelines for the use of anti-inflammatory agents for the prevention and treatment of oral mucositis in cancer patients. Materials and methods A systematic review was conducted by the Mucositis Study

  3. Melanoma: A model for testing new agents in combination therapies

    Directory of Open Access Journals (Sweden)

    Streicher Howard Z

    2010-04-01

    Full Text Available Abstract Treatment for both early and advanced melanoma has changed little since the introduction of interferon and IL-2 in the early 1990s. Recent data from trials testing targeted agents or immune modulators suggest the promise of new strategies to treat patients with advanced melanoma. These include a new generation of B-RAF inhibitors with greater selectivity for the mutant protein, c-Kit inhibitors, anti-angiogenesis agents, the immune modulators anti-CTLA4, anti-PD-1, and anti-CD40, and adoptive cellular therapies. The high success rate of mutant B-RAF and c-Kit inhibitors relies on the selection of patients with corresponding mutations. However, although response rates with small molecule inhibitors are high, most are not durable. Moreover, for a large subset of patients, reliable predictive biomarkers especially for immunologic modulators have not yet been identified. Progress may also depend on identifying additional molecular targets, which in turn depends upon a better understanding of the mechanisms leading to response or resistance. More challenging but equally important will be understanding how to optimize the treatment of individual patients using these active agents sequentially or in combination with each other, with other experimental treatment, or with traditional anticancer modalities such as chemotherapy, radiation, or surgery. Compared to the standard approach of developing new single agents for licensing in advanced disease, the identification and validation of patient specific and multi-modality treatments will require increased involvement by several stakeholders in designing trials aimed at identifying, even in early stages of drug development, the most effective way to use molecularly guided approaches to treat tumors as they evolve over time.

  4. Topical Hemostatic Agents: What the Oral and Maxillofacial Surgeon Needs to Know.

    Science.gov (United States)

    Vezeau, Patrick J

    2016-11-01

    Hemostasis is a key step in safe and predictable surgery. Knowledge of normal blood clotting mechanisms and abnormal diathesis is necessary to anticipate potential problems during and after surgery. As an adjunct to bleeding control, topical hemostatic agents have long been used in all surgical disciplines. This article provides a brief review of hemostasis and a topical summary of different classes of topical hemostatic agents useful to oral and maxillofacial surgery, including indications and potential complications/side effects. This rapidly evolving field promises to yield future agents with increased efficacy, cost efficiency, and decreased complications. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. 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.

  6. Persistent and recurrent tinea corporis in children treated with combination antifungal/ corticosteroid agents.

    Science.gov (United States)

    Alston, Sharonda J; Cohen, Bernard A; Braun, Marisa

    2003-01-01

    Combination antifungal/corticosteroid preparations are widely used by nondermatologists in the treatment of superficial fungal infections in patients of all ages. Over half of the prescriptions written for the most commonly used combination agent clotrimazole 1%/betamethasone diproprionate 0.05% cream (Lotrisone, Schering, Kenilworth, NJ) were prescribed for children younger than 4 years old. Our pediatric dermatology division has recently encountered a series of children with recurrent or persistent tinea corporis, especially tinea faciei, treated initially with combination antifungal/corticosteroid cream. All children evaluated for tinea corporis in a university hospital pediatric dermatology clinic from January through June 2001 were identified from the clinic registry for a retrospective chart review. Response to therapy was confirmed by telephone survey and/or follow-up visits at least 1 month after clearing of infection. Six children ranging in age from 4 to 11 years were evaluated for tinea corporis in a pediatric dermatology clinic at our institution during the 6-month period. All 6 children were diagnosed clinically by their pediatrician with tinea corporis and initially treated with clotrimazole 1%/betamethasone diproprionate 0.05% cream for 2 to 12 months. In our pediatric dermatology clinic, patients had their diagnosis confirmed with a positive potassium hydroxide preparation and were treated with one of several oral or topical antifungal agents with clearing of all tinea infections. The use of combination clotrimazole 1% cream/betamethasone diproprionate 0.05% cream (Lotrisone) for the treatment of tinea corporis may be associated with persistent/recurrent infection.

  7. Comparative study of the effects of two bleaching agents on oral microbiota.

    Science.gov (United States)

    Alkmin, Yara Tardelli; Sartorelli, Renata; Flório, Flávia Martão; Basting, Roberta Tarkany

    2005-01-01

    This study evaluated the in vivo effects of bleaching agents containing 10% carbamide peroxide (Platinum/Colgate) or 7.5% hydrogen peroxide (Day White 2Z/Discus Dental) on mutans Streptococcus during dental bleaching. The products were applied on 30 volunteers who needed dental bleaching. In each volunteer, one of the two bleaching agents was used on both dental arches one hour a day for three weeks. Analysis of the bacterial counts was made by collecting saliva before (baseline values), during (7 and 21 days) bleaching treatments and 14 days posttreatment. The Friedman non-parametric analysis (alpha=0.05) found no differences in microorganism counts at different times for each group for both agents (p>0.05). The Mann Whitney nonparametric test (alpha=0.05) showed no differences in micro-organism counts for both agents (p>0.05). Different bleaching agents did not change the oral cavity mutans Streptococcus counts.

  8. 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.

  9. 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

    : A total of 32 papers across 10 interventions were examined. New suggestions were developed against the use of systemic pilocarpine administered orally for prevention of OM during RT in head and neck cancer patients and in patients receiving high-dose chemotherapy, with or without total body irradiation......, prior to hematopoietic stem cell transplantation. A suggestion was also made against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed due to inadequate and...

  10. 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…

  11. Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation.

    Science.gov (United States)

    Moore, S Jo; West Greenlee, M Heather; Kondru, Naveen; Manne, Sireesha; Smith, Jodi D; Kunkle, Robert A; Kanthasamy, Anumantha; Greenlee, Justin J

    2017-10-01

    Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated (n = 20), orally inoculated (n = 19), and noninoculated (n = 9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled ("market weight" groups). The remaining pigs ("aged" groups) were allowed to incubate for up to 73 months postinoculation (mpi). Tissues collected at necropsy were examined for disease-associated prion protein (PrP(Sc)) by Western blotting (WB), antigen capture enzyme immunoassay (EIA), immunohistochemistry (IHC), and in vitro real-time quaking-induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC, and/or WB. By RT-QuIC, PrP(Sc) was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. The bioassay was positive in four out of five pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrP(Sc)) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months

  12. 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)

  13. [Reflections around the performance of community health agents in oral health strategies].

    Science.gov (United States)

    de Holanda, Ana Larissa Fernandes; Barbosa, Aldenísia Alves de Albuquerque; Brito, Ewerton William Gomes

    2009-10-01

    The Community Health Agent (CHA) has traditionally been linked to doctors and nurses, being considered exclusive 'property' of these professionals. Historically, oral health tended to operate isolated, disconnecting the mouth from the rest of the body and the individual from his environment. The Family Health Program (FHP) points to important changes in the organization of services as well as in the work process. One of the differences is the teamwork joining different professionals, including oral health which was previously excluded. The objective of the study is to show the experience of the CHA qualifying course, which allowed the entrance of different professional categories into teaching. The course included three odontologists as lecturers, and CHA recognized other individuals as health team members, as well as expand the view of its role within oral health. The professors also had their practices modified, given that they could understand the often ignored suffering and limitations of the CHAs.

  14. Herbal oral gel induced contact stomatitis along with desquamative gingivitis due to a coloring agent

    Directory of Open Access Journals (Sweden)

    Baljeet Singh

    2015-01-01

    Full Text Available Report of a rare case of contact stomatitis manifesting as irregular erosions partially covered with pseudomembrane along with desquamative gingivitis in a 32-year-old female patient is presented. The patient was otherwise healthy and not taking any medication. She gave the history of using curcumin-based oral gel 2 days back. Allergy test to curcumin oral gel was found to be positive, which on detailed allergy testing proved to be the coloring agent, erythrosine present in the gel. Contrary to the popular belief some folk medicine preparations can lead to unwanted side effects due to the antigenic potential of ingredients present in them. In addition, every clinician, during differential diagnosis of oral lesions must bear in mind unwanted reactions to any local ointment.

  15. Herbal oral gel induced contact stomatitis along with desquamative gingivitis due to a coloring agent.

    Science.gov (United States)

    Singh, Baljeet; Sharma, Alka; Garg, Avnika

    2015-01-01

    Report of a rare case of contact stomatitis manifesting as irregular erosions partially covered with pseudomembrane along with desquamative gingivitis in a 32-year-old female patient is presented. The patient was otherwise healthy and not taking any medication. She gave the history of using curcumin-based oral gel 2 days back. Allergy test to curcumin oral gel was found to be positive, which on detailed allergy testing proved to be the coloring agent, erythrosine present in the gel. Contrary to the popular belief some folk medicine preparations can lead to unwanted side effects due to the antigenic potential of ingredients present in them. In addition, every clinician, during differential diagnosis of oral lesions must bear in mind unwanted reactions to any local ointment.

  16. Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents

    OpenAIRE

    Dawed AY; Zhou K.; Pearson ER

    2016-01-01

    Adem Yesuf Dawed, Kaixin Zhou, Ewan Robert Pearson  Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, Scotland, UK Abstract: Type 2 diabetes is one of the leading causes of morbidity and mortality, consuming a significant proportion of public health spending. Oral hypoglycemic agents (OHAs) are the frontline treatment approaches after lifestyle changes. However, huge interindividual variation in response to OHAs resu...

  17. 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.

  18. Use of oral anti-diabetic agents in pregnancy: A pragmatic approach

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    Bharti Kalra

    2015-01-01

    Full Text Available Insulin is the gold standard for treatment of hyperglycemia during pregnancy, when lifestyle measures do not maintain glycemic control during pregnancy. However, recent studies have suggested that certain oral hypoglycemic agents (metformin and glyburide may be safe and be acceptable alternatives. There are no serious safety concerns with metformin, despite it crossing the placenta. Neonatal outcomes are also comparable, with benefit of reductions in neonatal hypoglycemia, maternal hypoglycemia and weight gain, and improved treatment satisfaction. Glibenclamide is more effective in lowering blood glucose in women with gestational diabetes, and with a lower treatment failure rate than metformin. Although generally well-tolerated, some studies have reported higher rates of pre-eclampsia, neonatal jaundice, longer stay in the neonatal care unit, macrosomia, and neonatal hypoglycaemia. There is also paucity of long-term follow-up data on children exposed to oral agents in utero. This review aims to provide an evidence-based approach, concordant with basic and clinical pharmacological knowledge, which will help medical practitioners use oral anti-diabetic agents in a rational and pragmatic manner. Pubmed search was made using Medical Subject Headings (MESH terms "Diabetes" and "Pregnancy" and "Glyburide"; "Diabetes" and "Pregnancy" and "Metformin". Limits were randomized controlled trials (RCTs and meta-analysis. The expert reviews on the topic were also used for discussion. Additional information (studies/review pertaining to discussion under sub-headings like safety during breastfeeding; placental transport; long-term safety data were searched (pubmed/cross-references/expert reviews.

  19. 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)

  20. Haematotoxic and reproductive toxicity of fixed dose combined anti-tuberculous agents: protective role of antioxidants in rats.

    Science.gov (United States)

    Awodele, O; Osunkalu, V O; Adejumo, I A; Odeyemi, A A; Ebuehi, O A T; Akintonwa, A

    2013-01-01

    Tuberculosis (TB) is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS. The major problem militating against the management of tuberculosis is the lack of compliance to medication by the infected patients as a result of multidrug needed to be taking daily leading to resistance. Occurrences of hepatic toxicity, teratogenicity, sperm quality damage, haematotoxicity and meningeal congestion of individual anti-tuberculous agents have been reported. The study is aimed to determine the reproductive and haematological toxicity of combined antituberculous agents and the modulatory role of antioxidants using animal model. Fifty rats (10 per group) were randomly allotted to five groups, consisting of the control, the fixed dose combined anti TB agents treated group, the fixed dose combined anti TB agents plus vitamin C treated group, the fixed dose combined anti TB agents plus vitamin E treated group and the fixed dose combined anti TB agents plus vitamin C plus vitamin E treated group. Therapeutic doses of the fixed dose combined anti TB agents (25 mg/kg/day), vitamin E (5 mg/kg) and vitamin C (8 mg/kg) were administered to the animals via oral gavage, daily over 28 days. After 28days, rats were sacrificed for internal macroscopic and histological examination of the organs, sperm analysis and haematological investigations were carried out. The results showed a significant increase (p < or = 0.05) in the levels of white blood cells (WBC), red blood cell (RBC) and haemoglobin (HB) of the combined anti-TB plus vitamins C or E treated groups compared with combined anti-TB treated group alone (56.34 +/- 0.11) that decreased the haematological parameters. A significant decrease (p < or = 0.05) in the sperm counts (22.26 +/- 0.02; 35.40 +/- 0.02) and motility (77.03 +/- 0.02; 94.50 +/- 0.01) of the combined anti-TB treated rats as compared with the control group were observed. The combined anti-TB plus

  1. Combination of Telmisartan with Cisplatin Controls Oral Cancer Cachexia in Rats

    Science.gov (United States)

    Patel, Bhoomika M.; Damle, Deepak

    2013-01-01

    The objective of the present investigation was to study the effect of combination of telmisartan with cisplatin in oral cancer cachexia induced by applying 0.5% 4-nitroquinoline-1-oxide (4-NQO) in propylene glycol to tongue, thrice a week for 8 weeks. From 8th to 22nd week, cisplatin (0.23 mg/kg, i.v.) was administered once in three weeks and telmisartan (5 mg/kg/day, p.o.) was administered daily. 4-NQO produced significant decrease in food intake, body weight, hyperglycemia, dyslipidemia, hypertension, and bradycardia, worsened hemodyanamics, increased cachexia markers like insulin, C-reactive protein, and interleukin-6, and increased tumor markers like lactate dehydrogenase and γ-glutamyl transferase.Treatment with combination of telmisartan with cisplatin produced significant increase in food intake and body weight and controlled hyperglycaemia and dyslipidemia, preserved hemodynamic function, and decreased the cachexia markers while cisplatin alone did not produce any increase in food intake and body weight. Further, the combination of telmisartan with cisplatin significantly reduced tumor marker levels. Combination of telmisartan with cisplatin prevented 4-NQO induced oxidative stress, hyperplasia and hyperkeratosis, premalignant dysplasia, and invasive squamous cell carcinoma in the tongue. Our data suggests that combination of telmisartan with cisplatin treatment is beneficial in controlling cancer cachexia. Telmisartan can be used as an add-on therapy with cisplatin or other traditional chemotherapeutic agents. PMID:24381940

  2. Difficult to swallow: issues affecting optimal adherence to oral anticancer agents.

    Science.gov (United States)

    Cheung, Winson Y

    2013-01-01

    The number of anticancer drugs currently available in oral formulation has increased dramatically over the past 15 to 20 years, especially with the recent development of new hormonal and targeted therapies. At present, approximately 25% of all cancer drugs are available in oral formulation, with numbers expected to increase exponentially in the coming years. The convenience associated with the self-administration of oral therapy, the requirement of fewer trips to the physician's office, and the lack of infusion reactions are all benefits for patients, allowing them to potentially maintain their relative independence while undergoing active anticancer treatment. On the other hand, there are growing concerns regarding patients' poor adherence to oral therapy as well as the challenges of monitoring patient compliance when treatment administration does not occur in the presence of health care professional (HCPs). More importantly, poor adherence to proven therapies may detrimentally affect the patients' clinical outcomes, such as survival. Thus, there is an urgent need to identify more effective strategies to measure and monitor adherence to oral anticancer agents in an effort to maximize their therapeutic benefits.

  3. Oral Contraceptive Pills: Combinations, Dosages and the Rationale behind 50 Years or Oral Hormonal Contraceptive Development

    Directory of Open Access Journals (Sweden)

    Rabe T

    2011-01-01

    symptoms, but also to find new compounds and formulas intended to replace those at the end of their patent lifespan. Methods of Good Clinical Practice have been established and large-scale epidemiological studies initiated (i.e. Study of the Royal College of General Practitioners, 1974 [566]. Several general approaches to OC development can be followed. Synthetic or natural estrogens provide a reliable cycle control and prevent estrogen deficiency symptoms due to the decreased secretion of endogenous estrogen from growth follicles. More selective, highly specific progestins have been developed with pharmacological properties similar to natural progesterone, some with antiandrogenic properties and suitable for transvaginal, transdermal, subdermal or intrauterine application. Furthermore, these new progestins produce fewer undesired effects on the breast and other reproductive organs and exhibit low carcinogenicity. Various additives have been tested for their additional non-contraceptive benefits (i.e. iron, folate, DHEA either by preventing certain undesired side effects of estrogens and progestins or by improving the general health status. Combinations of estrogen and progestin have evolved from monophasic to multiphasic formulations. Combination products require lower doses of steroids and provide a clinical profile similar to the normal menstrual cycle. New regimens (21 + 7, 22 + 6, 24 + 4, 84 + 7 with and without placebo pills or continuous administration have been used to maintain the contraceptive efficacy of the higher dose products and to achieve a stable bleeding pattern at lower doses. To date only Ortho-McNeil, Bayer HealthCare, MSD and Pfizer have been able to afford scientific research in the field of contraception and develop new products. The loss of patent lawsuits on their part, however, has allowed for the production of generic alternatives of oral contraceptives by other companies thus making it difficult for them to continue research in this specific

  4. 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.

  5. Headache induced by the use of combined oral contraceptives.

    Science.gov (United States)

    Allais, Gianni; Gabellari, Ilaria Castagnoli; Airola, Gisella; Borgogno, Paola; Schiapparelli, Paola; Benedetto, Chiara

    2009-05-01

    Although combined oral contraceptives (COCs) are a safe and highly effective method of birth control, they may also give rise to problems of clinical tolerability in migraine patients. Indeed, headache is among the most common side effects reported with the use of COCs, frequently leading to their being discontinued. The latest International Classification of Headache Disorders identified at least two entities evidently related to the use of COCs, i.e., exogenous hormone-induced headache and estrogen-withdrawal headache. As to the former, the newest formulations of COCs are generally well tolerated by migraine without aura patients, but can worsen headache in migraine with aura patients. Headache associated with COCs, generally, tends to improve as their use continues. However, although it is not yet clear if there is an association between headache and the composition of COCs (both in the type and amount of hormones), it has been observed that the incidence of headache during COC use seems greater if migraine is associated with menstrual trigger. The estrogen-withdrawal headache is a headache that generally appears within the first 5 days after cessation of estrogen use and resolves within 3 days, even if in some cases it may appear on the sixth or seventh day after pill suspension and lasts more than 3 days.

  6. 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.

  7. Adherence and patients' experiences with the use of oral anticancer agents.

    Science.gov (United States)

    Timmers, Lonneke; Boons, Christel C L M; Kropff, Femke; van de Ven, Peter M; Swart, Eleonora L; Smit, Egbert F; Zweegman, Sonja; Kroep, Judith R; Timmer-Bonte, Johanna N H; Boven, Epie; Hugtenburg, Jacqueline G

    2014-02-01

    A rapidly growing number of oral anticancer agents has become available in oncology and hematology. Though these introductions have several benefits, medication adherence is an issue of concern. Little is known about the factors influencing adherence to treatment with oral anticancer agents in daily practice. Material and methods. In this observational, multicenter study including 216 patients, carried out between October 2010 and March 2012, the use of oral anticancer drugs was assessed by means of a telephonic pill count, a questionnaire and a review of the patient's medical file and pharmacy medication records. Parameters collected were patients' demographics, treatment characteristics, beliefs and attitude towards disease and medicines, self-reported adherence, side effects, quality of life and satisfaction about information. Patients off treatment filled out a questionnaire about the reasons for discontinuation. Optimal adherence was defined as ≥ 95%-≤ 105%. Results. The mean adherence rate (AR) (n = 177) was 99.1% with 20.3% of patients having a sub-optimal AR ( 105%) consisting both of under- and over-adherence. Multivariate analyses showed that being on a cyclic dosing regimen (rather than a continuous regimen), not living alone and being highly educated increased the chances of optimal adherence (ORs = 4.88, 4.59 and 2.53, respectively). In addition, optimal adherence was found to be less common in patients reporting treatment control (OR = 0.77). One third of 79 patients off treatment reported their experienced side effects as one of the reasons for discontinuation. Discussion. Although most patients are fully adherent to oral anticancer agents, there is a substantial number tending to non-adherence. Patients living alone and those on a continuous dosing regimen are most likely to adhere sub-optimally. Interventions to improve adherence should specifically address these patients and be tailored to the needs of the individual patient.

  8. 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.

  9. 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.

  10. Oxidative Stress in Female Athletes Using Combined Oral Contraceptives.

    Science.gov (United States)

    Cauci, Sabina; Buligan, Cinzia; Marangone, Micaela; Francescato, Maria Pia

    2016-12-01

    Oxidative stress in female athletes is understudied. We investigated oxidative stress in sportswomen of different disciplines according to combined oral contraceptive (OC) use and lifestyle/alimentary habits. Italian sportswomen (n = 144; mean age 23.4 ± 4.2 years; body mass index 21.2 ± 2.2 kg m(-2); sport activity 9.2 ± 4.1 h week(-1)) were analyzed; 48 % were volleyball players, 12.5 % soccer players, 10.4 % track-and-field sports, and followed by other disciplines' athletes. Oxidative stress was evaluated by free oxygen radical test (FORT) assessing blood hydroperoxides and free oxygen radical defense (FORD) assay evaluating antioxidant capacity in OC users (n = 42) compared to non-OC users. Elevated oxidative stress levels (≥310 FORT units) were found in 92.9 % of OC users and in 23.5 % of non-OC users (crude OR = 42, 95 % CI 12-149, p correlated to hydroperoxides. In non-OC users only, hydroperoxide values were positively correlated with weight and BMI and inversely correlated with chocolate and fish consumption. The markedly elevated oxidative stress we revealed in OC-user athletes could be detrimental to physical activity and elevate cardiovascular risk (as thromboembolism). Further research is needed to extend our results, to clarify the biochemical pathways leading to increased hydroperoxides (mainly lipid peroxides) and reduced antioxidant defense, and to elucidate the potential effects on athletic performance. OC use should be considered when developing gender-focused strategies against oxidative stress.

  11. Pineapple juice as a negative oral contrast agent in magnetic resonance cholangiopancreatography: a preliminary evaluation.

    Science.gov (United States)

    Riordan, R D; Khonsari, M; Jeffries, J; Maskell, G F; Cook, P G

    2004-12-01

    The quality of magnetic resonance cholangiopancreatography (MRCP) images is frequently degraded by high signal from the gastrointestinal tract. The aim of this study is to evaluate pineapple juice (PJ) as an oral negative contrast agent in MRCP. Preliminary in vitro evaluation demonstrated that PJ shortened T(2) relaxation time and hence decreased T(2) signal intensity on a standard MRCP sequence to a similar degree to a commercially available negative contrast agent (ferumoxsil). Electrothermal atomic absorption spectrometry assay demonstrated a high manganese concentration in PJ of 2.76 mg dl(-1), which is likely to be responsible for its T(2) imaging properties. MRCP was subsequently performed in 10 healthy volunteers, before and at 15 min and 30 min following ingestion of 400 ml of PJ. Images were assessed blindly by two Consultant Radiologists using a standard grading technique based on contrast effect (degree of suppression of bowel signal), and image effect (diagnostic quality). There were statistically significant improvements in contrast and image effect between pre and post PJ images. There was particularly significant improvement in visualization of the pancreatic duct, but no significant difference between 15 min and 30 min post PJ images. Visualization of the ampulla, common bile duct, common hepatic and central intrahepatic ducts were also significantly improved at 15 min following PJ. Our results demonstrate that PJ, may be used as an alternative to commercially available negative oral contrast agent in MRCP.

  12. Effect of combination antiretroviral therapy on the frequency of oral candidiasis in HIV/AIDS patient

    Directory of Open Access Journals (Sweden)

    Sayuti Hasibuan

    2007-03-01

    Full Text Available Oral candidiasis is one of the most common opportunistic infections in HIV/AIDS patients. It serves as important markers of HIV infection, viral load, and CD4 cells count in the blood and predict disease progression to AIDS. The development of oral candidiasis in HIV/AIDS patients associated by imbalances between Candida and impaired host immune defenses that caused by decreased of CD4 cell counts and the increased of plasma HIV-viral load. Since the introduction of antiretroviral therapy combination, commonly known as Highly Active Antiretroviral Therapy (HAART, it has been observed that certain oral lesions, such as oral candidiasis as declined. The aim of this paper is to review the mechanism of combination antiretroviral therapy influenced the frequency of oral candidiasis in HIV/AIDS patient. We conclude that combination antiretroviral therapy generally reduced the frequency and severity of oral candidiasis in HIV/AIDS patient.

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

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    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.

  14. Combined oral contraceptive pills for treatment of acne.

    Science.gov (United States)

    Arowojolu, Ayodele O; Gallo, Maria F; Lopez, Laureen M; Grimes, David A

    2012-07-11

    Acne is a common skin disorder among women. Although no uniform approach to the management of acne exists, combination oral contraceptives (COCs), which contain an estrogen and a progestin, often are prescribed for women. To determine the effectiveness of combined oral contraceptives (COCs) for the treatment of facial acne compared to placebo or other active therapies. In January 2012, we searched for randomized controlled trials of COCs and acne in the computerized databases of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, and LILACS. We also searched for clinical trials in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) (Aug 2011). For the initial review, we wrote to researchers to seek any unpublished or published trials that we might have missed. We considered randomized controlled trials reported in any language that compared the effectiveness of a COC containing an estrogen and a progestin to placebo or another active therapy for acne in women. We extracted data on facial lesion counts, both total and specific (i.e., open or closed comedones, papules, pustules and nodules); acne severity grades; global assessments by the clinician or the participant, and discontinuation due to adverse events. Data were entered and analyzed in RevMan. For continuous data, we calculated the mean difference (MD) and 95% confidence interval (CI). For dichotomous data, we calculated the Peto odds ratio (OR) and 95% CI. The review includes 31 trials with 12,579 participants. Of 24 comparisons made, 6 compared a COC to placebo, 17 different COCs, and 1 compared a COC to an antibiotic. Of nine placebo-controlled trials with data for analysis, all showed COCs reduced acne lesion counts, severity grades and self-assessed acne compared to placebo. A levonorgestrel-COC group had fewer total lesion counts (MD -9.98; 95% CI -16.51 to -3.45), inflammatory and non-inflammatory lesion counts, and were more likely to

  15. Warfarin and Newer Agents: What the Oral Surgeon Needs to Know.

    Science.gov (United States)

    Steed, Martin B; Swanson, Matthew T

    2016-11-01

    The new direct oral anticoagulants-dabigatran etexilate, rivaroxaban, and apixaban- have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many surgeons are wary of these drugs, as there is limited evidence on how to manage bleeding in patients taking them, and only recently has a specific antidote been developed to reverse their anticoagulant effect. Management of the newer agents requires careful adherence to primary measures of bleeding care, knowledge of their mechanism of action, and familiarity with the unapproved and untested reversal strategies that may be required in patients with life-threatening bleeding. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Why develop antidotes and reversal agents for non-vitamin K oral anticoagulants?

    Science.gov (United States)

    Washam, Jeffrey B; Piccini, Jonathan P

    2016-02-01

    Over the past several years, non-vitamin K oral anticoagulants (NOACs) have been introduced into clinical practice for the treatment of venous thromboembolism and prevention of stroke in patients with nonvalvular atrial fibrillation. Clinical trials have shown these agents to have similar or less risk of major bleeding as compared to warfarin therapy. Moreover, when patients do experience a major bleeding event administration of advanced factor products is rare, and post-bleed outcomes are similar in those receiving a NOAC compared to those receiving warfarin. However, there are situations where urgent reversal of NOAC anticoagulation would be desirable. The following review focuses on the outcomes and management strategies for patients experiencing a major bleed with warfarin or NOAC agents and describes the rationale for the development of therapies capable of targeted NOAC-reversal.

  17. Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review

    Directory of Open Access Journals (Sweden)

    Takahiro Eitsuka

    2016-09-01

    Full Text Available Tocotrienol (T3, unsaturated vitamin E, is gaining a lot of attention owing to its potent anticancer effect, since its efficacy is much greater than that of tocopherol (Toc. Various factors are known to be involved in such antitumor action, including cell cycle arrest, apoptosis induction, antiangiogenesis, anti-metastasis, nuclear factor-κB suppression, and telomerase inhibition. Owing to a difference in the affinity of T3 and Toc for the α-tocopherol transfer protein, the bioavailability of orally ingested T3 is lower than that of Toc. Furthermore, cellular uptake of T3 is interrupted by coadministration of α-Toc in vitro and in vivo. Based on this, several studies are in progress to screen for molecules that can synergize with T3 in order to augment its potency. Combinations of T3 with chemotherapeutic drugs (e.g., statins, celecoxib, and gefitinib or dietary components (e.g., polyphenols, sesamin, and ferulic acid exhibit synergistic actions on cancer cell growth and signaling pathways. In this review, we summarize the current status of synergistic effects of T3 and an array of agents on cancer cells, and discuss their molecular mechanisms of action. These combination strategies would encourage further investigation and application in cancer prevention and therapy.

  18. Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review

    Science.gov (United States)

    Eitsuka, Takahiro; Tatewaki, Naoto; Nishida, Hiroshi; Nakagawa, Kiyotaka; Miyazawa, Teruo

    2016-01-01

    Tocotrienol (T3), unsaturated vitamin E, is gaining a lot of attention owing to its potent anticancer effect, since its efficacy is much greater than that of tocopherol (Toc). Various factors are known to be involved in such antitumor action, including cell cycle arrest, apoptosis induction, antiangiogenesis, anti-metastasis, nuclear factor-κB suppression, and telomerase inhibition. Owing to a difference in the affinity of T3 and Toc for the α-tocopherol transfer protein, the bioavailability of orally ingested T3 is lower than that of Toc. Furthermore, cellular uptake of T3 is interrupted by coadministration of α-Toc in vitro and in vivo. Based on this, several studies are in progress to screen for molecules that can synergize with T3 in order to augment its potency. Combinations of T3 with chemotherapeutic drugs (e.g., statins, celecoxib, and gefitinib) or dietary components (e.g., polyphenols, sesamin, and ferulic acid) exhibit synergistic actions on cancer cell growth and signaling pathways. In this review, we summarize the current status of synergistic effects of T3 and an array of agents on cancer cells, and discuss their molecular mechanisms of action. These combination strategies would encourage further investigation and application in cancer prevention and therapy. PMID:27669218

  19. Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents

    Directory of Open Access Journals (Sweden)

    Dawed AY

    2016-04-01

    Full Text Available Adem Yesuf Dawed, Kaixin Zhou, Ewan Robert Pearson  Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, Scotland, UK Abstract: Type 2 diabetes is one of the leading causes of morbidity and mortality, consuming a significant proportion of public health spending. Oral hypoglycemic agents (OHAs are the frontline treatment approaches after lifestyle changes. However, huge interindividual variation in response to OHAs results in unnecessary treatment failure. In addition to nongenetic factors, genetic factors are thought to contribute to much of such variability, highlighting the importance of the potential of pharmacogenetics to improve therapeutic outcome. Despite the presence of conflicting results, significant progress has been made in an effort to identify the genetic markers associated with pharmacokinetics, pharmacodynamics, and ultimately therapeutic response and/or adverse outcomes to OHAs. As such, this article presents a comprehensive review of current knowledge on pharmacogenetics of OHAs and provides insights into knowledge gaps and future directions. Keywords: pharmacogenetics, type 2 diabetes, oral hypoglycemic agents, pharmacokinetics, pharmacodynamics, response

  20. 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

  1. 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

  2. Orally Active and Selective Tubulin Inhibitors as Anti-Trypanosome Agents.

    Directory of Open Access Journals (Sweden)

    Vishal Nanavaty

    Full Text Available There is an urgent need to develop a safe, effective, orally active, and inexpensive therapy for African trypanosomiasis due to the drawbacks of current drugs. Selective tubulin inhibitors have the potential to be promising drug candidates for the treatment of this disease, which is based on the tubulin protein structural difference between mammalian and trypanosome cells. We propose to identify novel tubulin inhibitors from a compound library developed based on the lead compounds that selectively target trypanosomiasis.We used Trypanosoma brucei brucei as the parasite model, and human normal kidney cells and mouse microphage cells as the host model. Growth rates of both trypanosomes and mammalian cells were determined as a means to screen compounds that selectively inhibit the proliferation of parasites. Furthermore, we examined the cell cycle profile of the parasite and compared tubulin polymerization dynamics before and after the treatment using identified compounds. Last, in vivo anti-parasite activities of these compounds were determined in T. brucei-infected mice.Three compounds were selected that are 100 fold more effective against the growth of T. brucei cells than mammalian cells. These compounds caused cell cycle progression defects in T. brucei cells. Western analyses indicated that these compounds decreased tubulin polymerization in T. brucei cells. The in vivo investigation revealed that these compounds, when admitted orally, inhibited T. brucei cell proliferation in mouse blood. However, they were not potent enough to clear up the infection completely.These compounds are promising lead compounds as orally active agents for drug development of anti-trypanosome agents. A more detail structure activity relationship (SAR was summarized that will be used to guide future lead optimization to improve the selectivity and potency of the current compounds.

  3. 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.

  4. 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.

  5. Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shanshan Chen; Shun Lu 

    2015-01-01

    As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-smal cel lung cancer (NSCLC) and has proven ef ective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in com-bination with first-line chemotherapy for non-squamous NSCLC. Smal-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not al other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

  6. Pharmacokinetic interaction study between riociguat and the combined oral contraceptives levonorgestrel and ethinylestradiol in healthy postmenopausal women.

    Science.gov (United States)

    Frey, Reiner; Unger, Sigrun; van der Mey, Dorina; Becker, Corina; Saleh, Soundos; Wensing, Georg; Mück, Wolfgang

    2016-03-01

    Female patients requiring treatment for pulmonary arterial hypertension (PAH) are advised to avoid pregnancy because of the high associated mortality rate. Oral contraception is one of the main methods of preventing pregnancy in this context, mandating pharmacokinetic and safety studies for new agents in this setting. Riociguat is a soluble guanylate cyclase stimulator approved for treatment of PAH and inoperable and persistent or recurrent chronic thromboembolic pulmonary hypertension. This single-center, randomized, nonblinded study involving healthy postmenopausal women investigated the effect of riociguat on plasma concentrations of levonorgestrel (0.15 mg) and ethinylestradiol (0.03 mg) in a combined oral contraceptive. Treatment A was a single oral tablet of levonorgestrel-ethinylestradiol. In treatment B, subjects received 2.5 mg riociguat 3 times daily for 12 days. On the eighth day, they also received a single oral tablet of levonorgestrel-ethinylestradiol. Subjects received both regimens in a crossover design. There was no change in area under the plasma concentration-time curves of levonorgestrel or ethinylestradiol or maximum concentration in plasma (C max) of levonorgestrel during combined administration versus levonorgestrel-ethinylestradiol alone. A 20% increase in the C max of ethinylestradiol was noted during coadministration; this is not anticipated to adversely impact the contraceptive efficacy or to require any dose adjustment for ethinylestradiol. Plasma concentrations and exposures of riociguat were within the expected range and were not influenced by coadministration with levonorgestrel-ethinylestradiol. Combined treatment was safe and well tolerated. In conclusion, riociguat did not change the exposure to levonorgestrel or ethinylestradiol relative to oral contraceptive administered alone.

  7. Helical CT of the abdomen: whole milk as a low-density oral contrast agent; Tomografia helicoidal do abdome: avaliacao do leite integral como contraste oral de baixa densidade

    Energy Technology Data Exchange (ETDEWEB)

    Collares, Felipe Birchal; Diniz, Renata Lopes Furletti Caldeira; Motta, Emilia Guerra Pinto Coelho; Moreira, Wanderval; Ribeiro, Marcelo Almeida [Hospital Mater Dei, Belo Horizonte, MG (Brazil). Dept. de Radiologia

    2000-08-01

    We evaluated 90 abdominal helical computed tomography scans from patients who received 1% iodine solution, whole milk or no oral contrast agent before scanning. Four parameters were evaluated: gastrointestinal distension, mural visualization, pancreas-duodenum discrimination and bowel loop discrimination. Better results were obtained with the use of whole milk compared to iodine contrast or no oral contrast agent. Whole milk is an effective low density oral contrast agent. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Se Hyo; Cho, June Sik; Shin, Kyung Sook; Jeong, Ki Ho; Park, Jin Yong; Yu, Ho Jun; Kim, Young Min; Jeon, Kwang Jin [College of Medicine, Chungnam National University, Taejon (Korea, Republic of)

    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

  9. Antinociceptive synergy, additivity, and subadditivity with combinations of oral glucosamine plus nonopioid analgesics in mice.

    Science.gov (United States)

    Tallarida, Ronald J; Cowan, Alan; Raffa, Robert B

    2003-11-01

    Glucosamine (2-amino-2-deoxy-d-glucose) and glucosamine-containing products have been reported to have efficacy in the treatment of various musculoskeletal disorders. Glucosamine's efficacy, including reduction of pain, is attributed to disease-modifying properties, specifically to cartilage-rebuilding associated with modulation of interleukin-1-induced activation of chondrocytes and to inhibition of proinflammatory effects of the nuclear factor-kappaB pathway. However, glucosamine has not been shown to have direct analgesic activity. We report here that commercial glucosamine (90.4% glucosamine sulfate + 9.6% excipients) administered as the sole agent (up to 500 mg/kg p.o.) was inactive in the mouse abdominal irritant test but that certain combinations of glucosamine with nonopioid analgesics at the oral doses and ratios tested resulted in a synergistic (ibuprofen and ketoprofen), additive (diclofenac, indomethacin, naproxen, and piroxicam), or subadditive (aspirin and acetaminophen) antinociceptive interaction. In the specific case of ibuprofen, the racemate (standard ibuprofen) produced dose-related antinociception with ED50 = 26.1 +/- 3.4 mg/kg. Combinations containing racemic ibuprofen and glucosamine in greater than 1:1 ratio (glucosamine/ibuprofen) were synergistic in the test (e.g., ED50 = 11.0 +/- 2.1 for the 9:1 ratio; p < 0.01, analysis of variance). Combinations containing glucosamine and ibuprofen (2:1 and 9:1) yielded plasma levels of ibuprofen that were no different from administration of ibuprofen alone. The possibility that combinations containing certain fixed ratios of glucosamine and certain nonsteroidal anti-inflammatory drugs (NSAIDs) might enhance pain relief in patients with pain or might achieve acceptable levels of pain relief with lower doses of NSAIDs (reduced adverse effects) is presently being pursued in clinical trials.

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

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights ... Hypoglycaemic Agents in Type 2 Diabetes Mellitus Patients ... levels induced by several OHA cobmination regimens were documented. ... highlighting the important benefits conferred by the use of multiple OHAs.

  11. 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.

  12. 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...

  13. Efficacy of Black Tea as a Negative Oral Contrast Agent for MR Cholangiopancreatography (MRCP

    Directory of Open Access Journals (Sweden)

    Amir Hossein Jalali

    2010-05-01

    Full Text Available Background/Objective: Evaluation of the use of black tea as negative oral contrast agent in MR cholangiopancreatography (MRCP."nPatients and Methods: Thirty-five patients (mean age, 50.3±19.2 years, who were referred for MRCP, entered in this study. MRCP was performed before, after 5 minutes and after 15 minutes following consumption of 300 ml of black tea. Depiction of the gall bladder, cystic duct, proximal and distal parts of the common bile duct (CBD, intra hepatic ducts, ampula of Vater, main pancreatic duct (MPD and signal loss of the stomach and three different segments of the duodenum were investigated according to VAS and Lickert scores."nResults: Regarding visibility of seven different anatomical parts of the pancreatobiliary tree (gall bladder, cystic duct, CBD, common hepatic duct, intrahepatic duct, ampula of Vater and MPD, the post procedure images were better visualized only in the distal part of CBD, ampula of vater and MPD both in Lickert and VAS scoring (all Ps≤0.001."nThere was no significant difference between the images 5 and 15 minutes after tea consumption. Regarding the obliteration of high signal in the stomach and three different parts of the duodenum, all post tea images of the mentioned parts showed significant disappearance of high signal in Lickert and VAS scoring systems (all Ps≤0.001. "nConclusion: Black tea is an affordable, cheap, available, safe, and efficient oral negative contrast agent for MRCP which reduces the signal intensity of fluids in the gastrointestinal tract and is also efficient for better depiction of MPD, distal part of CBD and ampula.

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

    Energy Technology Data Exchange (ETDEWEB)

    Watarai, Jiro; Itagaki, Takatomo; Akutsu, Thoru; Yamaguchi, Kouichi; Kato, Isao (Yamagata Univ. (Japan))

    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.

  15. Direct oral anticoagulants and antiplatelet agents. Clinical relevance and options for laboratory testing.

    Science.gov (United States)

    Sibbing, D; Spannagl, M

    2014-01-01

    Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for antiplatelet treatment.

  16. Dabigatran and other oral antithrombotic agents for the prevention of stroke in patients with atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Testai F

    2011-06-01

    Full Text Available Fernando D Testai, Venkatesh AiyagariSection of Neurological Critical Care and Stroke, Department of Neurology and Rehabilitation, Center for Stroke Research, University of Illinois College of Medicine, Chicago, IL, USAAbstract: Atrial fibrillation (AF is considered to be one of the most prevalent abnormal heart rhythm disorders and a leading cause of cerebral ischemia. The risk of stroke in AF is associated with vascular risk factors including advancing age, hypertension, congestive heart disease, diabetes mellitus, vascular disease, and prior history of stroke or transient ischemic attack. The classic management of patients with AF at risk of suffering stroke includes the use of warfarin. The use of this medication in clinical practice is, however, limited owing to its narrow therapeutic window, multiple drug and food interactions, prolonged half-life, and the need for periodic anticoagulation monitoring. Recently, newer oral anticoagulants with better pharmacokinetic and pharmacodynamic profiles have been developed and compared to warfarin in phase III trials for the prevention of stroke and systemic embolism in patients with AF. Dabigatran stands out from these studies as a safe and efficacious alternative to warfarin for treating patients with AF at risk of stroke. In this article we review classic and novel approaches for stroke prevention in AF with special emphasis on dabigatran.Keywords: oral anticoagulants, vitamin K antagonists, antiplatelet agents, stroke prevention, atrial fibrillation

  17. Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners' Oral Contraception Study.

    Science.gov (United States)

    Iversen, Lisa; Sivasubramaniam, Selvaraj; Lee, Amanda J; Fielding, Shona; Hannaford, Philip C

    2017-06-01

    Oral contraceptives have been used by hundreds of millions of women around the world. Important questions remain regarding the very long-term cancer risks that are associated with oral contraception. Despite previous research, important questions remain about the safety of these contraceptives: (1) How long do endometrial, ovarian, and colorectal cancer benefits persist? (2) Does combined oral contraceptive use during the reproductive years produce new cancer risks later in life? (3) What is the overall balance of cancer among past users as they enter the later stages of their lives? The purpose of this study was to examine the very long-term cancer risks or benefits associated with the use of combined oral contraceptives, including the estimated overall life-time balance. The 46,022 women who were recruited to the UK Royal College of General Practitioners' Oral Contraception Study in 1968 and 1969 were observed for up to 44 years. Directly standardized rates of specific and any cancer were calculated for "ever" and "never" users of combined oral contraceptives; data were standardized for age, parity, social class, and smoking. Attributable risk and preventive fraction percentages were calculated. Poisson regression that adjusted for the same variables was used to estimate incidence rate ratios between ever and never users and to examine effects by time since last oral contraceptive use. There were 4661 ever users with at least 1 cancer during 884,895 woman-years of observation and 2341 never users with at least 1 cancer during 388,505 woman-years of observation. Ever use of oral contraceptives was associated with reduced colorectal (incidence rate ratio, 0.81; 99% confidence interval, 0.66-0.99), endometrial (incidence rate ratio, 0.66; 99% confidence interval, 0.48-0.89), ovarian (incidence rate ratio, 0.67; 99% confidence interval, 0.50-0.89), and lymphatic and hematopoietic cancer (incidence rate ratio, 0.74; 99% confidence interval, 0.58-0.94). An increased

  18. Small Bowel Obstruction Following Computed Tomography and Magnetic Resonance Enterography Using Psyllium Seed Husk As an Oral Contrast Agent

    Directory of Open Access Journals (Sweden)

    Yingming Amy Chen

    2014-01-01

    Full Text Available The authors report a case series describing four patients who developed small bowel obstruction following the use of psyllium seed husk as an oral contrast agent for computed tomography or magnetic resonance enterography. Radiologists who oversee computed tomography and magnetic resonance enterography should be aware of this potential complication when using psyllium seed husk and other bulking agents, particularly when imaging patients with known or suspected small bowel strictures or active inflammation.

  19. Small bowel obstruction following computed tomography and magnetic resonance enterography using psyllium seed husk as an oral contrast agent.

    Science.gov (United States)

    Chen, Yingming Amy; Cervini, Patrick; Kirpalani, Anish; Vlachou, Paraskevi A; Grover, Samir C; Colak, Errol

    2014-01-01

    The authors report a case series describing four patients who developed small bowel obstruction following the use of psyllium seed husk as an oral contrast agent for computed tomography or magnetic resonance enterography. Radiologists who oversee computed tomography and magnetic resonance enterography should be aware of this potential complication when using psyllium seed husk and other bulking agents, particularly when imaging patients with known or suspected small bowel strictures or active inflammation.

  20. 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.

  1. Analysis of FHS community health agents knowledge about oral health - doi: 10.4025/actascihealthsci.v35i2.11723

    Directory of Open Access Journals (Sweden)

    Nicole Patricia de Lima Vinagre

    2013-06-01

    Full Text Available The community health agents (CHA are considered health promoters in Brazilian communities teaching them about health promotion and disease prevention, including oral health. According to the Ministry of Health, CHAs must know about seven major oral health issues in Brazil. Thus, the objective of this study was to evaluate the oral health knowledge level of CHAs in the city of Belem, Pará State, Brazil. The study was based on a self-guided script, through a pre-prepared questionnaire containing 16 multiple-choice questions related to oral health knowledge. The survey was conducted with 94 agents from seven Family Health stations featuring oral health teams in Belem. It was concluded that community agents should be better prepared about oral care, as not all oral health issues were known by the CHAs oral health teams in Belem.

  2. Use of biologic agents in combination with other therapies for the treatment of psoriasis.

    Science.gov (United States)

    Cather, Jennifer C; Crowley, Jeffrey J

    2014-12-01

    Psoriasis is a chronic inflammatory skin disorder, which is associated with a significant negative impact on a patient's quality of life. Traditional therapies for psoriasis are often not able to meet desired treatment goals, and high-dose and/or long-term use is associated with toxicities that can result in end-organ damage. An improved understanding of the involvement of cytokines in the etiology of psoriasis has led to the development of biologic agents targeting tumor necrosis factor (TNF)-α and interleukins (ILs)-12/23. While biologic agents have improved treatment outcomes, they are not effective in all individuals with psoriasis. The combination of biologic agents with traditional therapies may provide improved therapeutic options for patients who inadequately respond to a single drug or when efficacy may be increased with supplementation of another treatment. In addition, combination therapy may reduce safety concerns and cumulative toxicity, as lower doses of individual agents may be efficacious when used together. This article reviews the current evidence available on the efficacy and safety of combining biologic agents with systemic therapies (methotrexate, cyclosporine, or retinoids) or with phototherapy, and the combination of biologic agents themselves. Guidance is provided to help physicians identify situations and the characteristics of patients who would benefit from combination therapy with a biologic agent. Finally, the potential clinical impact of biologic therapies in development (e.g., those targeting IL-17A, IL-17RA, or IL-23 alone) is analyzed.

  3. 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

  4. The effect of structured education to patients receiving oral agents for cancer treatment on medication adherence and self-efficacy

    Directory of Open Access Journals (Sweden)

    Gamze Tokdemir

    2017-01-01

    Full Text Available Objective: This study was conducted to examine the effect of structured education on medication adherence and self-efficacy through the use of the MASCC Oral Agent Teaching Tool (MOATT for patients receiving oral agents for cancer treatment. Methods: This quasi-experimental study has been conducted at two hospitals; 41 patients were included in the study. Data were obtained using a questionnaire, medication adherence self-efficacy scale (MASES, memorial symptom assessment scale, and a follow-up form (diary. Patients were educated through the use of the MOATT at a scheduled time; drug-specific information was provided along with a treatment scheme and follow-up diary. Phone interviews were completed 1 and 2 weeks after the educational session. At the next treatment cycle, the patients completed the same questionnaires. Results: Majority of the patients were receiving capecitabine (90.2%; n = 37 as an oral agent for breast (51.2%; n = 21 and stomach cancer (24.6%; n = 10 treatment. About 90.2% of patients (n = 37 stated that they did not forget to take their medication and experienced medication-related side effects (78%; n = 32. The total score of MASES was increased after the education (66.39 vs. 71.04, P < 0.05. Conclusions: It was shown that individual education with the MOATT and follow-up for patients receiving oral agents for cancer treatment increased patient medication adherence self-efficacy.

  5. 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 con

  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. Deep vein thrombosis in a woman taking oral combined contraceptive pills

    OpenAIRE

    2011-01-01

    Oral combined contraceptive pill (OCCP) is popular as birth control pills. Like all other drugs, they are not free from risks. Women taking certain types of OCCP have higher risk of developing deep vein thrombosis (DVT). A 29 year old married woman had taken OCCP for 3.5 months, developed deep vein thrombosis of left leg. Hereditary and acquired causes of DVT were excluded. She was treated with parenteral and oral anticoagulants simultaneously and was advised to discontinue OCCP. Initially th...

  8. Deep vein thrombosis in a woman taking oral combined contraceptive pills

    OpenAIRE

    Kiran G Piparva; Buch, Jatin G.

    2011-01-01

    Oral combined contraceptive pill (OCCP) is popular as birth control pills. Like all other drugs, they are not free from risks. Women taking certain types of OCCP have higher risk of developing deep vein thrombosis (DVT). A 29 year old married woman had taken OCCP for 3.5 months, developed deep vein thrombosis of left leg. Hereditary and acquired causes of DVT were excluded. She was treated with parenteral and oral anticoagulants simultaneously and was advised to discontinue OCCP. Initially th...

  9. Combined and sequential treatment of oral and maxillofacial malignancies: an evolving concept and clinical protocol

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jia-wei; QIU Wei-liu; ZHANG Zhi-yuan

    2008-01-01

    Objective To introduce the concept and rational regimens and present the latest development of combined treatment of oral and maxillofacial malignancies.Data sources The related published literature was searched through the CNKI database and MEDLINE using the terms of oral cancer, oral and maxillofacial malignancies, combined and sequential therapy, multidisciplinary approach.Study selection The available related literature was read and evaluated. Studies that met the inclusion criteria were selected.Results The results show that oral and maxillofacial malignancies diagnosed at an eady stages (stages Ⅰ and Ⅱ) can be well treated with surgery alone and/or radiotherapy with optimal outcome, but advanced or recurrent diseases should be treated with rational combined and sequential treatment modalities. The use of concomitant chemoradiotherapy,taxane-containing, three-drug induction regimens and Cetuximab in combination with chemotherapy or radiotherapy demonstrated favorable results in previously untreated patients with head and neck squamous cell carcinoma.Conclusions The concept of combined and sequential treatment of advanced oral and maxillofacial malignancies should be widely accepted, and the rational regimen for individual and each type of entity should be determined based on the anatomical site and the patient's performance status.

  10. 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.

  11. Hepatoprotective role of neutrosecR on hepatic damage induced by combination of zidovudine and combined anti-tuberculous agents in rats.

    Science.gov (United States)

    Awodele, Olufunsho; Agbaje, Esther O; Adesina, Enitan A; Akintonwa, Alade

    2011-07-20

    Advent of the HIV/AIDS pandemic has led to a dramatic increase in the number of TB cases worldwide. Availability of highly active antiretroviral therapy (HAART) has significantly improved the outcome of HIV/AIDS, in terms of prevention of opportunistic infections (OIs) as well as mortality however; liver toxicity is one of the most relevant adverse effects of antiretroviral therapy (ART). In view of the inevitable use of zidovudine (a common ART) and antituberculous fixed-dose combination therapy (FDCs) in the management of HIV-TB co-infection and the resultant hepatotoxicity, this study was aimed to investigate the hepatoprotective role of neutrosec (a combination of aminoacid and vitamins) on the hepatotoxicity induced by co-administration of zidovudine and combined fixed dose antituberculous agents. Twenty four rats were randomly allotted to four groups, consisting of the control, zidovudine plus fixed dose combined anti TB agents treated group, zidovudine plus fixed dose combined anti TB agents plus neutrosec treated group and neutrosec alone treated group. Therapeutic doses of zidovudine (8.5 mg/kg/day), fixed dose combined anti TB agents (25 mg/kg/day) and neutrosec (0.4 ml/kg/day) were administered to the animals via oral gavage, daily over 60 days. After 60 days, rats were sacrificed for internal macroscopic and histological examination of the liver. The liver enzyme parameters (AST, ALP, Total bilirubin, Total protein, Albumin) were determined using fully automated clinical chemistry analyzer (Hitachi 912, Boehringer Mannheim, Germany). Antioxidant enzymes activity and lipid peroxidation were determined according to standard procedures. The AST results showed a significant (p ≤ 0.05) decreased in the zidovudine plus anti-TB plus neutrosec treated group (125.50 ± 22.71) compared with zidovudine plus anti-TB treated group (399. 10 ± 0.45). It further showed non-significant decreased (p ≥ 0.05) in the ALP levels between the zidovudine plus anti TB

  12. Insulin versus an oral antidiabetic agent as add-on therapy in type 2 diabetes after failure of an oral antidiabetic regimen: a meta-analysis

    OpenAIRE

    Gamble, JM; Simpson, Scot H.; Brown, Lauren C.; Johnson, Jeffrey A

    2008-01-01

    Background Although evidence-based guidelines for the treatment of type 2 diabetes mellitus provide clear recommendations for initial therapy, evidence on an optimal treatment strategy after secondary failure is unclear. Purpose To compare the efficacy of add-on therapy using basal insulin versus an additional oral antidiabetic agent in patients with type 2 diabetes and secondary failure. Data sources We searched the following electronic databases from inception until June 2007: MEDLINE; EMBA...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-07-01

    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 {sup 10}B(n,a){sup 7}Li reaction products is very short, 10-14 {mu}m 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 {sup 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 {sup 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)

  14. Use of combination of leflunomide with biological agents in treatment of rheumatoid arthritis.

    NARCIS (Netherlands)

    Kalden, J.R.; Antoni, C.; Alvaro-Gracia, J.M.; Combe, B.; Emery, P.; Kremer, J.M.J.; Strand, C.V.; Riel, P.L.C.M. van; Smolen, J.S.

    2005-01-01

    An Expert Panel Meeting was held in May 2004 to assess experience with combination therapy with leflunomide and biological agents in the treatment of rheumatoid arthritis (RA), to identify both optimal use of such combinations and precautions for use. Eleven published prospective or retrospective st

  15. A COMPARISON OF MIDAZOLAM AND KETAMINE PLUS MIDAZOLAM COMBINATION AS AN ORAL PREMEDICANT IN PAEDIATRIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Krishna Prabu

    2014-08-01

    Full Text Available INTRODUCTION: Effective premedication in pediatric patients posted for elective surgeries allays patients’ anxiety and reduces risk of post-operative behavioral problems. Oral midazolam and oral ketamine are tried in different doses as pediatric premedicant, but addition of 3mg/kg of oral ketamine with 0.5 mg/kg of oral midazolam resulted in better premedication when compared to oral midazolam 0.5mg/kg or oral ketamine 6mg/kg given alone. MATERIAL AND METHODS: 60 healthy children under 1-8 yrs. age group posted for elective surgeries chosen for this study were randomly divided into two groups of 30 each. Double blinding was done using sealed envelope technique to prevent observer bias. Children with other co-existing illnesses were excluded from the study. Group KM received Ketamine 3 mg/kg and midazolam 0.5 mg/kg + atropine 20 µg/kg (oral route and Group M received midazolam 0.5 mg/kg and atropine 20 µg/kg (oral route 30 minutes before proposed induction time. Sedation score, anxiolysis score, parental separation and mask tolerance was assessed in all the patients 30 minutes after administration of the drug. RESULTS: The data collected was analyzed using SPSS statistical software. There was a statistically significant increase in sedation score at 15 and 30 minutes in group KM compared to group M. Parental separation at 30 minutes is peaceful in 30 children (100% in group KM compared to 24 children (80% in group M. CONCLUSION: The oral ketamine and midazolam combination produces significantly better anxiolysis, sedation, parental separation and mask tolerance, without hemodynamic alteration, when compared to oral midazolam (0.5mg/kg given alone.

  16. Acute oral toxicity and histopathological study of combination of endosulfan and cypermethrin in wistar rats.

    Science.gov (United States)

    Raj, Jaya; Mohineesh; Ray, Ruma; Dogra, T D; Raina, Anupuma

    2013-01-01

    Endosulfan, a neurotoxic organochlorine insecticide and cypermethrin, a synthetic pyrethroid insecticide used to control pests in domestic, industrial, and agricultural situations. The present study was carried out to investigate the acute oral toxicity, behavioral and histopathological changes of combination of endosulfan and cypermethrin in albino rats. According to Miller and Tainter analysis method, at 48 h, LD50 value of combination of endosulfan and cypermethrin (ratio 1:1) in rats was found to be 691.83 mg/kg bw by oral gavage. When combination of both these pesticides was administered orally at concentration of 103.72 mg/kg bw, 172.95 mg/kg bw and 207.50 mg/kg bw, respectively, as a single dose, no significant changes in behavior of rats was observed, neither in dosed nor in control group of rats. Combination of endosulfan- and cypermethrin-treated rats showed mild histopathological changes in liver and kidney in group IV (207.50 mg/kg BW) as compared to the control. However, no significant changes were observed in brain and small intestine at either dose of combination of endosulfan and cypermethrin with respect to control. Thus, the present study, first of its kind in India, demonstrated the oral toxicity, behavioral, and histo-architectual alterations after induction of combination of endosulfan and cypermethrin at acute doses in Wistar rats.

  17. Therapeutic efficacy of the combination of intratympanic methylprednisolone and oral steroid for idiopathic sudden deafness.

    Science.gov (United States)

    Gundogan, Onur; Pinar, Ercan; Imre, Abdulkadir; Ozturkcan, Sedat; Cokmez, Ozge; Yigiter, Ali Cihan

    2013-11-01

    The purpose of this study was to compare the efficacy of systemic steroid alone and combined with intratympanic methylprednisolone in the treatment of patients with idiopathic sudden sensorineural hearing loss. Prospective, randomized controlled trial. Settings Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey. Seventy-nine patients who met the inclusion criteria for idiopathic sudden sensorineural hearing loss were included in this study. Patients were randomly divided into 2 groups according to treatment: group A received combination therapy (intratympanic methylprednisolone + oral steroid) and group B received oral steroid alone. Of the 79 patients included, 6 patients missed the 1-month follow-up visit. Overall, 73 patients (37 combination group, 36 oral steroid group) who completed the 1-month follow-up and study intervention were included in the per-protocol analysis. Both the relationship between certain prognostic factors and the clinical outcome after treatment were analyzed. Combination therapy showed significant hearing improvement and speech discrimination scores compared with the use of systemic steroids alone (P < .05). In hearing outcomes in patients with severe hearing loss, combination therapy had statistically significant hearing improvement compared with oral steroid alone (P < .05). We recommend that combination therapy can be considered as initial treatment especially for patients with severe hearing loss.

  18. Use of combined oral contraceptive pills among teenage girls in Calabar, Nigeria

    Directory of Open Access Journals (Sweden)

    Iklaki CU

    2012-07-01

    Full Text Available Christopher U Iklaki,1 John E Inaku,2 John E Ekabua,1 Patience O Odusolu,1 Charles O Njoku11Department of Obstetrics and Gynaecology, University of Calabar, Calabar, Nigeria; 2Department of Obstetrics and Gynaecology, University of Calabar Teaching Hospital, Calabar, NigeriaAbstract: The objective of this study was to find out about the use of combined oral contraceptive pills by women in Calabar, Nigeria, with a particular interest in single nulliparous teenage women. During the period from 2006 to 2010, a total of 1980 women seen in the University of Calabar Teaching Hospital's family planning unit used various methods of contraception. Of these, 316 (15.96% used combined oral contraceptive pills. Twenty girls aged between 13 and 19 years accounted for 6.3% of those who used combined oral contraceptive pills. There were 296 (93.6% women between the ages of 20 and 34 years who accounted for the remaining users. Of these women, 195 (61.5% were educated to the secondary level, and 34 (10.8% were educated to primary level. No women without formal education used combined oral contraceptive pills during the period of study. The majority of the users were nulliparous (128; 40.4%; the rest had parity values of at least one to more than four. One hundred thirty-seven (43.4% of the users were single, 112 (35.4% were married, and the remaining 67 (21.1% were separated, divorced, or widowed. There is a growing need to educate young Nigerian women about the use of combined oral contraceptive pills; this medication is suitable and effective for most young women, and it also has additional noncontraceptive health benefits.Keywords: combined, oral, contraception, pills

  19. Poor adherence with ACE inhibitors is a risk factor of CVA with oral hypoglycemic agents in diabetic patients.

    Science.gov (United States)

    Aftab, Muhammad Tariq; Dharamshi, Hasnain Abbas; Faraz, Ahmed; Shakeel, Saba; Shakeel, Osama

    2017-03-01

    Poor adherence with medicine declines the clinical outcome of pharmacotherapy. It may carry serious sequelae especially in case of antihypertensive drugs like cerebrovascular accident (CVA). This study has been planned to find the association of poor adherence with anti-hypertensive with CVA in diabetic and non- diabetic patients. One hundred CVA patients who were admitted through Emergency in Abbasi Shaheed hospital, a tertiary care hospital in Karachi, were recruited from Jun 2013 till Dec 2013. The criteria of inclusion was, diagnosed case of CVA, with primary hypertension, availability of patient's therapeutic record, consent of the patient or legal successor/heir. The criteria of exclusion was, secondary hypertension, newly diagnosed primary hypertensive patients and complete adherence with medication. Morisky medication adherence scale was applied. Therapeutic record was accessed. The mean age was 62.15 years with 3:1 male to female ratio. Adherence to medicine was graded 0.05) was seen in any combination (p>0.05). Thus it is concluded that poor adherence with ACE inhibitors may be a risk factor of CVA in diabetic patients using oral hypoglycemic agents.

  20. In silico attempt for adduct agent(s) against malaria: Combination of chloroquine with alkaloids of Adhatoda vasica.

    Science.gov (United States)

    Swain, Shasank S; Sahu, Mahesh C; Padhy, Rabindra N

    2015-10-01

    With the aim of controlling drug resistant Plasmodium falciparum, a computational attempt of designing novel adduct antimalarial drugs through the molecular docking method of combining chloroquine with five alkaloids, individually is presented. These alkaloids were obtained from the medicinal plant, Adhatoda vasica. From the obtained individual docking values of important derivatives of quinine and chloroquine, as well as, individual alkaloids and adduct agents of chloroquine with Adhatoda alkaloids as ligands, it was discernible that the 'adduct agent-1 with chloroquine and adhatodine' combination had the minimum energy of interaction, as the docking score value of -11.144 kcal/mol against the target protein, triosephosphate isomerase (TIM), the key enzyme of glycolytic pathway. Drug resistance of P. falciparum is due to a mutation in the polypeptide of TIM. Moratorium of mutant TIM would disrupt the metabolism during the control of the drug resistant P. falciparum. This in silico work helped to locate the 'adduct agent-1 with chloroquine and adhatodine', which could be taken up by pharmacology for further development of this compound as a new drug against drug resistant Plasmodium.

  1. Use of pharmacy dispensing data to measure adherence and identify nonadherence with oral hypoglycemic agents.

    Science.gov (United States)

    Sodihardjo-Yuen, Fong; van Dijk, Liset; Wensing, Michel; De Smet, Peter A G M; Teichert, Martina

    2017-02-01

    A framework for calculation of adherence for oral hypoglycemic agents (OHAs) based on data from health-insurance claims is available. Pharmacy dispensing data aid identification of nonadherent patients in pharmacy practices. However, use of these data for calculation of OHA adherence requires additional methodological categories. We examined the impact of different methodological choices on estimation of OHA adherence using pharmacy dispensing data. Four methodological categories were added to the framework available to be used for adherence calculation with pharmacy dispensing data. Three adherence measures were defined to supply pharmacists with significant information on OHA use of their patients: (i) percentage of days covered by use periods of dispensed medication (PDC), (ii) mean rate of adherent patients with a PDC ≥80 % (MRAP80), and (iii) mean number of nonadherent patients (MNNP80) per pharmacy with a PDC pharmacies in the Netherlands. For the basic scenario, mean PDC for OHA was 88.3 %. MRAP80 was 80.3 %, which corresponded to an average of 69 nonadherent patients per pharmacy. Different choices for parameter values resulted in score variations for PDC of 85.0-91.8 %, for MRAP80 of 75.3-86.1 %, and between 49 and 92 MNNP80 per pharmacy. Sixteen methodological categories specified calculation of OHA adherence based on pharmacy dispensing data. Adherence scores expressed as percentages were relatively robust to variation in parameter values, but differed substantially for the absolute numbers of nonadherent patients per pharmacy.

  2. [Effect of new oral antimicrobial agents in outpatient treatment of pneumonia in children].

    Science.gov (United States)

    Ouchi, Kazunobu; Sunakawa, Keisuke

    2014-06-01

    In November 2004, "Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan" was published ahead of the rest of the world, by Japanese Society of Pediatric Pulmonology/Japanese Society for Pediatric Infectious Diseases, based on the data on causative organisms in the lower respiratory tract. In its 2011 version, classification of the severity of pneumonia was renewed based on the latest information. As a result, many types of pneumonia in children are now classified as mild or moderate. This means that many patients who might have conventionally required hospital treatment can now be managed on an outpatient basis. The reason for realization of the wider range of outpatient treatment is the availability of two new oral antimicrobial agents, tebipenem pivoxil and tosufloxacin tosilate hydrate, for the treatment of infections in children. Analysis of data on medical expenses shows a decreased rate of hospitalization due to pneumonia year by year after launch of these two drugs, suggesting that these drugs have contributed to wider range of outpatient treatment. This manuscript discusses the effect of tebipenem pivoxil and tosufloxacin tosilate hydrate in the treatment of pneumonia.

  3. Comparative adherence to oral hormonal agents in older women with breast cancer.

    Science.gov (United States)

    Cheung, Winson Y; Lai, Edward Chia-Cheng; Ruan, Jenny Y; Chang, Jennifer T; Setoguchi, Soko

    2015-07-01

    We aim to (1) compare compliance of anastrozole, letrozole, exemestane, and tamoxifen in women and (2) identify clinical factors associated with medication non-adherence and non-persistence. Female Medicare beneficiaries who were new users of anastrozole, letrozole, exemestane, or tamoxifen between 2007 and 2010 were analyzed. Multivariate-modified Poisson and Cox regression models were constructed to compare non-adherence and non-persistence, respectively, across the different oral agents. A total of 5,150 women were included: mean age was 76.4 years, 2352 initiated anastrozole, 1401 letrozole, 248 exemestane, and 1149 tamoxifen. Non-adherence and non-persistence were 41 and 49% respectively, with exemestane being associated with the worst non-adherence and non-persistence (RR 1.57, 95% CI 1.37-1.80, p adherence (RR 0.89, 95 % CI 0.82-0.96, p = 0.002 and RR 0.84, 95 % CI 0.76-0.92, p adherence) and persistence (HR 0.86, 95 % CI 0.79-0.94, p adherence and persistence in older women with breast cancer.

  4. The novel microtubule targeting agent BAL101553 in combination with radiotherapy in treatment-refractory tumor models.

    Science.gov (United States)

    Sharma, Ashish; Broggini-Tenzer, Angela; Vuong, Van; Messikommer, Alessandra; Nytko, Katarzyna J; Guckenberger, Matthias; Bachmann, Felix; Lane, Heidi A; Pruschy, Martin

    2017-09-01

    Resistance to microtubule targeting agents (MTA) represents a major drawback in successful cancer therapy with MTAs. Here we investigated the combined treatment modality of the novel MTA BAL101553 in combination with radiotherapy in paclitaxel and epothilone-resistant tumor models. Multiple regimens of BAL101553, or its active moiety BAL27862 for in vitro experiments, were probed in combination with radiotherapy in P-glycoprotein-overexpressing, human colon adenocarcinoma cells (SW480) and in tubulin-mutated human NSCLC cells (A549EpoB40) and tumors thereof. BAL27862 reduced the proliferative activity of SW480 and A549EpoB40 tumor cells with similar potency as in A549 wildtype cells. Combined treatment of BAL27862 with ionizing radiation in vitro resulted in an additive reduction of clonogenicity. Moreover, treatment of paclitaxel- and epothilone-resistant tumors with fractionated irradiation and different regimens of BAL101553 (a single i.v. bolus vs. oral daily) suppressed tumor growth and resulted in an extended additive tumor growth delay with strong reduction of tumor proliferation and mean tumor vessel density. BAL101553 is a promising alternative in taxane- and epothilone-refractory tumors as part of a combined treatment modality with ionizing radiation. Its potent antitumor effect is not only tumor cell-directed but also targets the tumor microenvironment. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Effects of combination oral care on oral health, dry mouth and salivary pH of intubated patients: A randomized controlled trial.

    Science.gov (United States)

    Jang, Chun Sun; Shin, Yong Soon

    2016-10-01

    Intubated patients are at risk of oral health problems. Although a variety of oral care regimens for intubated patients have been studied, there is a lack of research on the effects of combination oral care that includes tooth brushing, chlorhexidine and cold water. This open-labelled, randomized, controlled trial aimed to evaluate the effects of combination oral care on oral health status. Participants aged 20 years and older were recruited on the first day after intubation through convenience sampling in a medical intensive care unit. Random assignment was performed using an internet randomization service. The primary outcome was oral health status. Data were collected during May and June 2013. Participants were randomized to one of two groups (23 intervention and 21 control). The final analysis included 18 patients with combination oral care and 17 in the control group. The intervention group had better oral health (effect size = 1.56), less dry mouth and higher salivary pH than the control group. Any additional burden of providing combination oral care to patients who are mechanically ventilated is worthwhile in terms of clinical outcomes.

  6. Efektifitas Astaxanthin Oral disertai Gel Astaxanthin Dibandingkan dengan Astaxanthin Oral disertai Krim Triple Combination (Hidrokuinon 4%, Tretinoin 0,05%, Fluosinolon Asetonid 0,01%) dalam Pengobatan Melasma

    OpenAIRE

    Lubis, Faridah Israwaty

    2011-01-01

    Background : Melasma is a common acquired symmetrical hypermelanosis that occurs on sun-exposed facial areas. Melasma is frequently observed among women. Many modalities of treatment are available but none is satisfactory. Aim : To compare the efficacy and safety of oral astaxanthin combined with astaxanthin gel and oral astaxanthin combined with triple combination cream in the treatment of melasma. Subject and methods : A double blind, randomize, clinical trial design study was condu...

  7. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2011-01-01

    Full Text Available Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

  8. Realizing the Potential of Vascular Targeted Therapy: The Rationale for Combining Vascular Disrupting Agents and Anti-Angiogenic Agents to Treat Cancer.

    Science.gov (United States)

    Siemann, D W; Chaplin, D J; Horsman, M R

    2017-09-14

    Vascular targeted therapies (VTTs) are agents that target tumor vasculature and can be classified into two categories: those that inhibit angiogenesis and those that directly interfere with established tumor vasculature. Although both the anti-angiogenic agents (AAs) and the vascular disrupting agents (VDAs) target tumor vasculature, they differ in their mechanism of action and therapeutic application. Combining these two agents may realize the full potential of VTT and produce an effective therapeutic regimen. Here, we review AAs and VDAs (monotherapy and in combination with conventional therapies). We also discuss the rationale of combined VTT and its potential to treat cancer.

  9. Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive : II. Clinical effects

    NARCIS (Netherlands)

    Zimmerman, Y.; Foidart, J. M.; Pintiaux, A.; Minon, J. M.; Fauser, B. C J M; Cobey, K.; Coelingh Bennink, H. J T

    2015-01-01

    Objectives Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that 'co-administration' of dehydroepiandrosterone (DHEA) to a drospirenone (DRSP)-containing COC

  10. Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive : I. Endocrine effects

    NARCIS (Netherlands)

    Zimmerman, Y.; Foidart, J. M.; Pintiaux, A.; Minon, J. M.; Fauser, B. C J M; Cobey, K.; Coelingh Bennink, H. J T

    2015-01-01

    Objectives Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). Study design In this randomized, double-blind, placebo-controlled study

  11. [DVT and combined oral contraceptives: update of the pluridisciplinary CNGOF-FNCGM-GEHT-SFMV group].

    Science.gov (United States)

    Chabbert-Buffet, N; Guigues, B; Trillot, N; Biron, C; Morange, P; Pernod, G; Scheffler, M; Brugere, S; Hedon, B

    2013-06-01

    Thrombotic risk among combined oral contraceptives (COC) users has recently been debated following a court action initiated by a patient. Recent epidemiological data, as well as accumulating biological data underlying these data, have led French Health authorities to modify COC prescription and reimbursement modalities. A short synthesis is proposed by a multidisciplinary group of experts from four French societies (CGOF, FNCGM, GHT, and SFMV).

  12. 甘精胰岛素联合口服降糖药物对血糖控制不佳的2型糖尿病患者的疗效观察%Efficacy of insulin glargine combined with oral hypoglycemic agent in type 2 diabetic patients with poor glycemic control

    Institute of Scientific and Technical Information of China (English)

    徐迎侠; 刘洪英

    2011-01-01

    Objective To investigate the efficacy and safety of insulin glargine(lantus(R))combined with metformin and pioglitazone in type 2 diabetic patients whose blood glucose levels Were inadequately controlled by oral antidiabetic drugs(OAD).Methods 78 type 2 diabetic patients with poor glycemic control of OAD were randomly divided into group A and B.Patients in group A and B received insulin glargine and NPH insulin respectively in addition to OAD of metformin and pioglitazone.Fasting blood glucose(FBG),2-bour postprandial blood glucose(2 hVG),glycosylated hemoglobin(Hb)A1c and the increase of weight,as well as hypoglycemia rate were abserved after therapy.Results Levels of FBG,2 hPG and HbA1c were lower in group A than those in group B(P0.05).Conclusion The treatment of insulin glargine with metformin and piglitazone in type 2 diabetic patients with poor glycemic control is more efficient.As the basic insulin treatment,glarglne Was more efficient than NPH insulin.%目的 评价甘精胰岛素(来得时(R))与盐酸吡格列酮和二甲双胍联合应用治疗口服降糖药物控制不佳的2型糖尿病患者的有效性和安全性.方法 采用随机法将78例口服降糖药物控制不佳的2型糖尿病患者分为A、B两组.A组为甘精胰岛素(来得时(R))组,B组为精蛋白锌胰岛素(诺和灵N)组,两组均口服吡格列酮和二甲双胍,观察治疗后空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(Hb)A1c水平,以及体重增加值和低血糖发生率.结果 A组FBG、2 hPG及HbA1c水平均低于B组(P均0.05).结论 口服降糖药物疗效差的2型糖尿病患者应用甘精胰岛素联合吡咯列酮和二甲双胍治疗,有更显著的降糖效果;作为基础胰岛素治疗,甘精胰岛素优于精蛋白锌胰岛素.

  13. Pharmacoeconomic comparison of ziprasidone with other atypical oral antipsychotic agents in schizophrenia

    Directory of Open Access Journals (Sweden)

    Andrea Fagiolini

    2011-03-01

    Full Text Available Objective: to comparatively investigate – by means of computer simulations – the economic cost and clinical outcomes of five atypical oral antipsychotic agents (ziprasidone, olanzapina, risperidone, paliperidone and aripiprazolo.Methods: a cyclical stochastic model representing patient evolution, taking into account main adverse reactions (akathisia, weight gain and extra-pyramidal ARs, drug efficacy on psychosis stabilization and probability of relapse, was developed. Ten different scenarios were compared, each starting with one of the considered antipsychotics, prescribed either at home or in a hospital setting. Switching to another medication was allowed until no untried drugs were available, in which case clozapine treatment or admission to a Psychiatric Therapeutic Rehabilitation Center were irreversibly assigned. Model inputs were probabilities of ARs, probabilities of stabilization and probabilities of destabilization (assumed equal for all; as well as costs attributable to drugs, hospitalization, outpatient care and costs adverse reactions in terms of concomitant medications. Sources for the inputs were the trials reported in the most recent literature (from the year 2000, selected based on the homogeneity of the observational period and antipsychotic dosage used.Results: in each scenario, the hospitalization cost represented the highest component of the overall cost (approximately 67%. Assuming equal drug effectiveness, ziprasidone fared better than all other considered competitors, showing the lowest average annual costs per patient (and also the lowest average annual hospitalization costs as well as the largest numbers of controlled months without adverse reactions, independently of the initial setting. Conclusions: the most important determinant of total cost appears to be hospitalization, whose cost is about 600% higher than the medications cost. Medication effectiveness and tolerability remain however of utmost importance for

  14. Cardiovascular disease and oral agent glucose-lowering therapies in the management of type 2 diabetes.

    Science.gov (United States)

    Home, Philip

    2012-06-01

    Although glucose-lowering oral agents have been available for clinical use for over 60 years, the formal evidence base supporting their advantage and safety in regard of cardiovascular (CV) outcomes remains less than optimal. However, a synthesis of the evidence results in a high probability of benefit. For metformin, the United Kingdom Prospective Diabetes Study (UKPDS) substudy is convincing for a definite effect in reducing myocardial infarction (MI), but the quantitative extent of that is uncertain. For sulfonylureas, support for reduction in MI comes from the UKPDS extension study, where the central estimate for risk reduction remains the same as in the original planned end to the study, but the greater number of events was statistically significant for the sulfonylurea/insulin arm. Other studies do not support the view that metformin and sulfonylureas differ with respect to MI or indeed CV outcomes more generally. The data available for acarbose, an α-glucosidase inhibitor, are weak but not of concern, although some positive substudy data are available for people with impaired glucose tolerance. For peroxisome proliferator-activated receptor-γ agonists the CV data are more controversial, but the purpose-designed randomized controlled trials are clear that pioglitazone is advantageous to placebo (except for heart failure [HF]), whereas rosiglitazone is indistinguishable from metformin/sulfonylureas (even when including HF data). Lower-quality data do, however, lead to significant concerns for MI with rosiglitazone. Early and somewhat low-quality data for the dipeptidyl peptidase inhibitors show they are safe and hold promise for cardiovascular advantage, with major randomized controlled trials being underway. Preliminary CV data are available for one sodium/glucose cotransporter 2 inhibitor and look reassuring.

  15. N-succinyl chitosan as buccal penetration enhancer for delivery of herbal agents in treatment of oral mucositis.

    Science.gov (United States)

    Dhawan, Neha; Kumar, Krishan; Kalia, A N; Arora, Saahil

    2014-01-01

    Oral mucositis is one of the major side effects of cancer chemotherapy (30-76%) and radiotherapy (over 50%). Current palliative treatments of oral mucositis include specialized agents like pelifermin, platelet derived factors etc. or oral hygienic agents which suffered from various drawbacks like systemic side effect, least effect owing to fast wash out of buccal mucosa, patient unfriendly delivery systems, and mere symptomatic relief. In this research work, N-succinyl chitosan gel delivery system of microemulsified eugenol, honey and sodium hyaluronate was prepared to explore their multiple and synergistic effects on various pathological factors of oral mucositis. N-succinyl chitosan was synthesized in our laboratory and loaded with microemulsified eugenol (10% v/v), honey (10% v/v) and sodium hyaluronate (0.2% w/v) to prepare orogel with optimum pH, spreadability, mucoadhesion strength, and viscosity. In vitro eugenol release from N-succinyl chitosan gel after 8 hours in PBS (pH-6.4) was found to be 87.45±0.14%, which was better in comparison to that released from chitosan gel. Ex vivo penetration studies using rat buccal mucosal tissue also suggested better J-efflux of eugenol through N-succinyl chitosan in comparison to chitosan gel with enhancement ratio (ER) of 1.71. The antimicrobial effect of N-succinyl chitosan based orogel against S. aureus and C. albicans efficacy was found to be statistically high in comparison to chitosan based orogel as well as marketed formulation of chlorhexidine (pgel formulation within 15 days. The formulation was successful in elevating the survival and reducing the inflammation in the oral mucosa of animals compared to disease control (p<0.05) and hence suggesting the potential of N-succinyl chitosan orogel in the treatment of oral mucositis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Joergensen, Jan Troest [Research and Development, CMC Contrast AB, Scion DTU, Lyngby (Denmark)], email: jtj@cmc-contrast.dk; Rief, Matthias; Wagner, Moritz [Dept. of Radiology, Charite - Universitaetsmedizin Berlin, Berlin (Germany); Brismar, Torkel B.; Albiin, Nils [Dept. of Radiology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden)

    2012-09-15

    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.

  17. A new manganese-based oral contrast agent (CMC-001) for liver MRI: pharmacological and pharmaceutical aspects.

    Science.gov (United States)

    Jørgensen, Jan Trøst; Rief, Matthias; Brismar, Torkel B; Wagner, Moritz; Albiin, Nils

    2012-09-01

    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 D(3), 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.

  18. Combined oral and local therapy for the dissolution of urinary calculi.

    Science.gov (United States)

    Götz, F; Frang, D; Hübler, J; Nagy, Z

    1982-01-01

    The factors underlying the formation of Ca-phosphate and struvite calculi, as well as the present possibilities for oral and local therapy, their advantages and drawbacks are discussed in the light of published evidence. In this context a clinical case of multiple injuries is reported in which practically complete chemolitholysis has been achieved by combined oral and local therapy. The rapid growth of the calculi and their alarming tendency to recurrence in case of inadequate treatment is emphasized. The therapeutic method used in this case is regarded as suitable for practical purposes.

  19. 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.

  20. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

    Energy Technology Data Exchange (ETDEWEB)

    Ataman, Ozlem U., E-mail: ouataman@hotmail.com [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Sambrook, Sally J. [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Wilks, Chris [Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Lloyd, Andrew [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Taylor, Amanda E. [Yellow Delaney Communications Ltd, Wilmslow, Cheshire (United Kingdom); Wedge, Stephen R. [Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom)

    2012-11-15

    Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that

  1. Enhanced bioavailability of a poorly water-soluble weakly basic compound using a combination approach of solubilization agents and precipitation inhibitors: a case study.

    Science.gov (United States)

    Li, Shu; Pollock-Dove, Crystal; Dong, Liang C; Chen, Jing; Creasey, Abla A; Dai, Wei-Guo

    2012-05-07

    Poorly water-soluble weakly basic compounds which are solubilized in gastric fluid are likely to precipitate after the solution empties from the stomach into the small intestine, leading to a low oral bioavailability. In this study, we reported an approach of combining solubilization agents and precipitation inhibitors to produce a supersaturated drug concentration and to prolong such a drug concentration for an extended period of time for an optimal absorption, thereby improving oral bioavailability of poorly water-soluble drugs. A weakly basic compound from Johnson and Johnson Pharmaceutical Research and Development was used as a model compound. A parallel microscreening precipitation method using 96-well plates and a TECAN robot was used to assess the precipitation of the tested compound in the simulated gastric fluid (SGF) and the simulated intestinal fluid (SIF), respectively, for lead solubilizing agents and precipitation inhibitors. The precipitation screening results showed vitamin E TPGS was an effective solubilizing agent and Pluronic F127 was a potent precipitation inhibitor for the tested compound. Interestingly, the combination of Pluronic F127 with vitamin E TPGS resulted in a synergistic effect in prolonging compound concentration upon dilution in SIF. In addition, HPMC E5 and Eudragit L100-55 were found to be effective precipitation inhibitors for the tested compounds in SGF. Furthermore, optimization DOE study results suggested a formulation sweet spot comprising HPMC, Eudragit L 100-55, vitamin E TPGS, and Pluronic F127. The lead formulation maintained the tested compound concentration at 300 μg/mL upon dilution in SIF, and more than 70% of the compound remained solubilized compared with the compound alone at <1 μg/mL of its concentration. Dosing of the solid dosage form predissolved in SGF in dogs resulted in 52% of oral bioavailability compared to 26% for the suspension control, a statistically significant increase (p = 0.002). The enhanced

  2. 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

  3. 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.

  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. 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.

  6. 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.)

  7. Factors Associated with Long-Term Oral Hypoglycemic Agent Responsiveness in Korean Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Bo-Yeon Kim

    2011-06-01

    Full Text Available BackgroundThis study was performed to determine the factors associated with long-term oral hypoglycemic agent (OHA responsiveness in Korean type 2 diabetic patients.MethodsTwo groups of patients were selected among the type 2 diabetic patients who were followed for more than two years at a university hospital diabetes clinic. The OHA responsive group consisted of 197 patients whose HbA1c levels were maintained at ≤7% with OHA for more than two years. The OHA failure group consisted of 180 patients whose HbA1c levels were >8% in spite of optimal combined OHA therapy or patients who required insulin therapy within the two years of the study.ResultsThe OHA failure group had higher baseline values of fasting and postprandial glucose, HbA1c, and lower fasting, postprandial, and delta C-peptide compared to those of the OHA responsive group. The OHA failure group also had a higher proportion of female patients, longer diabetic duration, and more family history of diabetes. There were no significant differences in body mass index (BMI or insulin resistance index between the two groups. Multiple logistic regression analysis showed that the highest quartile of baseline fasting, postprandial glucose, and HbA1c and the lowest quartile of postprandial and delta C-peptide were associated with an increased odds ratio of OHA failure after adjustment for age, sex, body mass index, and family history of diabetes.ConclusionLower baseline values of postprandial and delta C-peptide and elevated fasting glucose and HbA1c are associated with long-term OHA responsiveness in Korean patients with type 2 diabetes mellitus.

  8. 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.

  9. Treatment of oral malodour. Medium-term efficacy of mechanical and/or chemical agents: a systematic review

    NARCIS (Netherlands)

    Slot, D.E.; van der Geest, S.; van der Weijden, F.A.; Quirynen, M.

    2015-01-01

    Focused question What is the effect of a dentifrice (DF), a mouthwash (MW), tongue cleaning (TC), or any combination of these as adjunct to toothbrushing on intra-oral malodour and tongue coating as compared to toothbrushing alone in systemically healthy patients, when used for a minimum follow-up p

  10. Childhood vitiligo : Response to methylprednisolone oral minipulse therapy and topical fluticasone combination

    Directory of Open Access Journals (Sweden)

    Majid Imran

    2009-01-01

    Full Text Available Background: Childhood vitiligo is always a challenge to treat, especially when the disease is progressing rapidly in such a patient. Oral minipulse with betamethasone has been tried in childhood vitiligo and also in some other immune mediated skin disorders with good results. Aims: The aim of the present study was to see the overall efficacy of methylprednisolone oral minipulse therapy in combination with topical fluticasone in progressive childhood vitiligo. The combination was tried to achieve a significant amount of repigmentation of vitiligo lesions already present at the initial visit. Materials and Methods: Four hundred children with progressive vitiligo were enrolled for this study and were prescribed oral methylprednisolone on two consecutive days every week in a minipulse form for a period of six months. In addition, the patients were instructed to apply fluticasone ointment topically once a day on their vitiligo lesions. The patients were assessed for the remission achieved as well as the extent of repigmentation of their already existent lesions. Results: More than 90% of patients went into complete remission after the start of the therapy. Moreover, about 65% (two-thirds of patients achieved good to excellent repigmentation of lesions at the end of six months of therapy. The therapy was also well tolerated and the side effects seen were almost negligible. Conclusions: Oral minipulse treatment with methylprednisolone is an effective treatment option for controlling the disease spread in childhood vitiligo and with the addition of topical fluticasone the extent of repigmentation achieved is also quite significant.

  11. 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.

  12. In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood.

    Science.gov (United States)

    Chang, S C; Chen, Y C; Luh, K T; Hsieh, W C

    1995-11-01

    In vitro activities of 15 antimicrobial agents against 90 strains of Acinetobacter baumannii isolated from blood cultures from hospitalized patients were determined using the agar dilution method. Imipenem, ofloxacin, and ciprofloxacin had the best antimicrobial activity with minimum inhibitory concentrations (MIC50s) of 0.25 mu g/ml and MIC90s of 0.5-1 mu g/ml. beta-lactam antibiotics other than imipenem had poor activity, with MIC50s ranging from 8 to 64 mu g/ml and MIC90s from 32 to > or = 256 mu g/ml. The checkerboard titration method was used to study the effects of combination of two antimicrobial agents. Combinations of ceftazidime, aztreonam, imipenem, or ciprofloxacin with amikacin showed either synergistic effects or partial synergistic effects for 40.9%-86.4% of 22 tested strains. The best in vitro activity was observed with the combination of imipenem and amikacin. No antagonistic effects were observed with the combination of imipenem and amikacin. Synergistic effects were confirmed by time-kill curve studies. In conclusion, imipenem, ofloxacin, and ciprofloxacin were the three most active agents against human blood isolates of A. baumannii. The combination of a beta-lactam or ciprofloxacin with amikacin was synergistic for some of the isolates.

  13. Antimicrobial activity of clinically used antiseptics and wound irrigating agents in combination with wound dressings.

    Science.gov (United States)

    Hirsch, Tobias; Limoochi-Deli, Simin; Lahmer, Armin; Jacobsen, Frank; Goertz, Ole; Steinau, Hans-Ulrich; Seipp, Hans-Martin; Steinstraesser, Lars

    2011-04-01

    A primary strategy for preventing and treating wound infection in chronic wounds is the use of topical antiseptics and wound irrigating agents. However, their interaction with commonly used wound dressings has not yet been investigated. In this study, the authors analyzed the antimicrobial activity of antiseptics and wound irrigating agents used with commercially available wound dressings. Five clinically used antiseptics and wound irrigating agents (Prontosan, Lavasept, Braunol, Octenisept, and Betaisodona) were tested in the presence or absence of 42 wound dressings against Staphylococcus aureus. The determination of antibacterial activity was performed by disk diffusion assay. Povidone-iodine-based products showed sufficient antimicrobial activity in 64 to 78 percent of the combinations assessed (p > 0.01). The octenidine derivate Octenisept showed sufficient antimicrobial activity in 54 percent of combinations. Polyhexamethylene biguanide derivatives demonstrated sufficient antimicrobial activity in 32 percent of the combinations. This study revealed that commonly used wound dressings dramatically reduce antibacterial activity of clinically used antiseptics and wound irrigating agents in vitro.

  14. Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary

    OpenAIRE

    Ryoko Takahashi; Seiji Mabuchi; Mahiru Kawano; Tomoyuki Sasano; Yuri Matsumoto; Hiromasa Kuroda; Katsumi Kozasa; Kae Hashimoto; Kenjiro Sawada; Tadashi Kimura

    2016-01-01

    Objective The objective of this study was to evaluate the antitumor effects of lurbinectedin as a single agent or in combination with existing anticancer agents for clear cell carcinoma (CCC) of the ovary, which is regarded as an aggressive, chemoresistant, histological subtype. Methods Using human ovarian CCC cell lines, the antitumor effects of lurbinectedin, SN-38, doxorubicin, cisplatin, and paclitaxel as single agents were assessed using the MTS assay. Then, the antitumor effects of comb...

  15. Preschool teachers as agents of oral health promotion: an intervention study in Sri Lanka.

    Science.gov (United States)

    Fernando, S; Kanthi, R D F C; Johnson, N W

    2013-09-01

    According to National Oral Health Survey reports and research, Early Childhood Caries has been identified as a serious public health problem in Sri Lanka. More than 65% of preschool-aged children have dental decay and only 2% of them have had treatment. With proper interventions and commitment from public health personnel and responsible community leaders this should be a largely preventable disease. An intervention study was conducted among preschool teachers in the District of Colombo, Sri Lanka, to assess their influence on oral health promotion in the school environment. All the available 52 preschools and all 72 teachers registered under a local government authority were involved in the study. Preschools were divided into intervention group and control group based on geographically defined areas. The intervention included training preschool teachers using a manual covering health education, health promotion, incorporation of oral-health-friendly activities into the preschool curriculum, and hands-on experience of oral examination. Pre- and post- assessments were conducted with a 6 month interval. After 6 months, the median oral health knowledge score of the intervention group improved from 55 to 72 (p = 0.005) and the mean score for oral health related practices from 32 to 35 (p = 0.032). The variables: oral-health-friendly preschool environment (p = 0.02), availability of brushing facilities (p = 0.005) and availability of information, education and communication materials related to oral health (p = 0.004) were significantly different between the two groups after 6 months. Oral health promotion activities can be effectively instilled in a pre-school environment by the education of teachers.

  16. [Biochemical composition of oral rehydration solutions and their combinations suggested for use in Venezuela].

    Science.gov (United States)

    Goyo-Rivas, J J; Rendón, F

    1989-03-01

    We studied the electrolyte composition, pH and osmolality of six solutions for oral rehydration available in drug stores in Venezuela, and also their combinations with whole milk in a dilution of 6.6%. The solutions such as Pedialyte, Hidramilac and Hidramines showed an acid pH (4.30-5.10) in direct relationship to the concentration of carbohydrates (5% or more). Also, Pedialyte and Hidramilac had greater osmolalities (360-365 mOsm/kg) than plasma. Some of the levels of sodium and potassium in the solutions were found to be under the concentrations given by the producers. The combination of whole milk with oral solutions diminishes the concentrations of sodium and potassium in the mixture, changing the sodium-glucose relationship, pH and osmolality. The therapeutic implications for the use of oral rehydration solutions with low concentrations of sodium, acid pH, large content of glucose and elevated osmolality are discussed. It is concluded that the combination of whole milk with Sueroral (WHO) is not adequate for the optimum absorption of sodium and therefore to prevent dehydration. Therefore, except for the WHO solution and Oralite, other solutions are not adequate for the correction of the electrolytic and acid-base alterations present in infants with dehydration secondary to acute diarrhea.

  17. Study of combination treatment effect of the {sup 166}Ho and anticancer agents in-vitro

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, S. M.; Choi, S. J.; Park, K. B. [KAERI, Taejon (Korea, Republic of)

    2003-10-01

    For the development of new controlled drug delivery systems, the application of combination therapy using radioisotopes and tumor static agents has drawn great attention. This study was designed to estimate the treatment effect of the combination therapy with Holmium ({sup 166}Ho) and tumor static agents. Ho-166 was produced at the KAERI using HANARO reactor. The drugs applied were Sunpla, Methotrexate and Doxorubicin. Human glioblastoma (T98G), adenocarcinoma (MKN45), hepatocellular (Hep3B), lung carcinoma (Calu6), ovary adenocarcinoma (NIH:OVCAR- 3) and rat glioma (C6) were used. The cell cytotoxicity on the tumor cell lines determined by MTT assay. In the case where the chemotherapeutic agent was solely applied to the cell lines, the IC{sub 50} values wer e 2.4x10{sup -5}M of the Sunpla for MKN45 and 4.23x10{sup -6}M of the Doxorubicin for Calu6. The radioactivity of Ho-166 occurring 20% apoptosis was 10{mu}Ci. As for Sunpla and Doxorubicin, the value of IC20 was dependent on the cell lines used. The combination treatment of {sup 166}Ho and drug was to improve therapeutic success rate in T98G, MKN45, Hep3B, and Calu6. From this in vitro study it can be concluded that combining 166Ho radionuclide therapy and chemotherapy could enhance the effect of each in eliminating proliferating tumor cells.

  18. 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.

  19. Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer-bearing dogs.

    Science.gov (United States)

    Allstadt Frazier, S; McKemie, D S; Guerrero, T A; LaChapelle, H; Skorupski, K A; Kass, P H; Rodriguez, C O

    2014-03-01

    Rosiglitazone is an FDA-approved peroxisome proliferator-activated receptor gamma (PPARγ) agonist and antidiabetic agent in humans that has been investigated for its ability to reduce tumor cell growth. The purpose of this study was to determine the maximally tolerated dose, peak plasma concentrations and side effect profile of oral rosiglitazone when combined with carboplatin in dogs with cancer. Rosiglitazone was administered at 6 and 8 mg/m(2) to seven dogs. Carboplatin was administered at 240-300 mg/m(2) in combination with rosiglitazone. For toxicity evaluation, the toxicity data for the seven dogs in this study were combined with the toxicity data from three dogs previously reported in a methodology study. Peak plasma rosiglitazone concentrations varied with dose. The dose-limiting toxicity was hepatic at a dose of 8 mg/m(2). Three dogs had mild to moderate alanine aminotransferase elevations but no changes in total bilirubin, alkaline phosphatase, blood glucose or γ-glutamyltranspeptidase values were noted.

  20. Combined use of renin-angiotensin-aldosterone system-acting agents: a cross-sectional study.

    Science.gov (United States)

    Farcas, Andreea; Leucuta, Daniel; Bucsa, Camelia; Mogosan, Cristina; Dumitrascu, Dan

    2016-12-01

    Background Due to recent EU warnings and restrictions on the combined use of renin-angiotensin-aldosterone system (RAAS)-acting agents, and the seriousness of the associated harm, we analyzed the prescription of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) as dual therapy or associated with spironolactone. Setting An administrative claims database of a regional hospital in Romania. Methods We retrospectively included all adult patients hospitalized during 18 months in 2013-2014, discharged with a prescription of a RAAS-acting agent. Main outcome measures Counts of ACEIs and ARBs co-prescription, of ACEIs or ARBs combined with spironolactone, co-morbidities, co-medication, creatinine, and electrolytes assessment and values. Results Out of 1697 patients with a prescription of a RAAS-acting agent, 24 (1.4 %) were co-prescribed ACEIs and ARBs, and 416 (24.5 %) ACEIs or ARBs with spironolactone. Patients prescribed dual ACEI/ARB therapy and the ones with ACEI or ARB-spironolactone combination had significantly higher prevalence of increased creatinine level before discharge, compared to the ACEI and ARB monotherapy groups (48 and 31 % compared to 17 and 27 %). Subjects with diabetes, heart failure, ischaemic heart disease, or urea ≥40 mg/dL had higher odds of having ACEI or ARB-spironolactone combination compared to monotherapy, while hypertension and renal disease subjects had lower odds. Similar findings were comparing dual ACEI/ARB therapy to monotherapy except heart failure (not statistically significant). Conclusion Overall, the prevalence of use of dual therapy was low. The combined use of RAAS-acting agents was higher in patients with known risk factors for further renal function deterioration, compared to the ones without.

  1. In vitro potency and combination testing of antimicrobial agents against Neisseria gonorrhoeae.

    Science.gov (United States)

    Bharat, Amrita; Martin, Irene; Zhanel, George G; Mulvey, Michael R

    2016-03-01

    Antimicrobial resistant Neisseria gonorrhoeae is a major concern to public health due to decreased susceptibility to frontline antimicrobials. To find agents that are active against N. gonorrhoeae, we tested antimicrobials alone or in combination by Etest gradient strips. The potencies (as assessed by minimum inhibitory concentrations) of twenty-five antimicrobials were evaluated against nine reference strains of N. gonorrhoeae (WHO F, G, K, L, M, N, O, P and ATCC 49226). Potency was greatest for netilmicin, quinupristin-dalfopristin, ceftriaxone, ertapenem and piperacillin-tazobactam. Combinations of azithromycin, moxifloxacin, or gentamicin with ceftriaxone, doripenem, or aztreonam were tested against reference isolates and the fractional inhibitory concentration index (FICI) was calculated. All nine combinations resulted in indifference (>0.5 FICI ≤ 4). Combinations with FICI gonorrhoeae. These data on antimicrobials with higher potency and combinations that did not show antagonism can help to guide larger scale susceptibility studies for antimicrobial resistant N. gonorrhoeae.

  2. 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

  3. Antioxidant agents: a future alternative approach in the prevention and treatment of radiation-induced oral mucositis?

    Science.gov (United States)

    de Freitas Cuba, Letícia; Salum, Fernanda Gonçalves; Cherubini, Karen; de Figueiredo, Maria Antonia Zancanaro

    2015-01-01

    Radiotherapy is a therapeutic modality frequently employed for patients with head and neck cancer (HNC). It destroys tumor cells, but it is not selective, also affecting healthy tissues and producing adverse effects. One that stands out is oral mucositis because of the morbidity that it is capable of causing. This lesion is characterized by the presence of erythema, ulcerations, pain, opportunistic infections, and weight loss. These side effects can lead to serious situations that require the interruption of the antineoplastic treatment and can result in hospitalization and even death. The complex mechanisms linked to the pathogenesis of oral mucositis were recently established, and since then, the control of oxidative stress (OS) has been tied to the prevention and management of this disease. The authors have carried out a review of the literature about the use of antioxidant agents in the prevention and treatment of radiation-induced oral mucositis, using the PubMed database. This review has shown that the research on use of antioxidants (AOX) has proved insufficient to justify suggesting the products in treatment protocols. Results are promising, however, and AOX may represent a future alternative in the prevention and treatment of oral mucositis.

  4. Analysis of in vitro chemoprevention of genotoxic damage by phytochemicals, as single agents or as combinations.

    Science.gov (United States)

    Abraham, Suresh K; Eckhardt, Alexander; Oli, Rajaraman G; Stopper, Helga

    2012-05-15

    Cancer chemoprevention with low-dose combinations of bioactive phytochemicals instead of single agents has been suggested to induce less toxicity and improve efficacy. In this study, we selected four plant food-based phytochemicals, viz. chlorogenic acid (CLA), pelargonidin (PEL), resveratrol (RES) and epigallocatechin gallate (EGCG) to evaluate the in vitro chemoprevention of genotoxic damage in HL-60 cells. These agents were tested either individually or as a combination at two concentrations (with a 10-fold difference) against the genotoxins mitomycin C (MMC), diepoxybutane (DEB) and patulin (PAT). Our preliminary ferric reducing antioxidant power (FRAP) assay demonstrated additive effects when PEL, CLA, RES and EGCG were combined. Results of the cytokinesis-block micronucleus test showed significant protection against genotoxic damage induced by PAT, DEB and MMC when CLA, PEL, RES and EGCG were tested individually. This protective effect of the phytochemicals was not concentration-related. Both low- and high-concentration combinations of CLA, PEL, RES and EGCG showed significant reducing effects on the frequencies of micronuclei induced by PAT, DEB and MMC. However, the micronucleus test did not provide indications of additive or synergistic effects with this combination of phytochemicals. In conclusion, the chemo-preventive effects of PEL, CLA, RES and EGCG against genotoxic damage induced by MMC, DEB and PAT are indicative of a 'saturation effect' when higher concentrations and combinations of these phytochemicals are used.

  5. Influence of mycotoxins and a mycotoxin adsorbing agent on the oral bioavailability of commonly used antibiotics in pigs.

    Science.gov (United States)

    Goossens, Joline; Vandenbroucke, Virginie; Pasmans, Frank; De Baere, Siegrid; Devreese, Mathias; Osselaere, Ann; Verbrugghe, Elin; Haesebrouck, Freddy; De Saeger, Sarah; Eeckhout, Mia; Audenaert, Kris; Haesaert, Geert; De Backer, Patrick; Croubels, Siska

    2012-04-01

    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.

  6. Discovery of wall teichoic acid inhibitors as potential anti-MRSA β-lactam combination agents.

    Science.gov (United States)

    Wang, Hao; Gill, Charles J; Lee, Sang H; Mann, Paul; Zuck, Paul; Meredith, Timothy C; Murgolo, Nicholas; She, Xinwei; Kales, Susan; Liang, Lianzhu; Liu, Jenny; Wu, Jin; Santa Maria, John; Su, Jing; Pan, Jianping; Hailey, Judy; Mcguinness, Debra; Tan, Christopher M; Flattery, Amy; Walker, Suzanne; Black, Todd; Roemer, Terry

    2013-02-21

    Innovative strategies are needed to combat drug resistance associated with methicillin-resistant Staphylococcus aureus (MRSA). Here, we investigate the potential of wall teichoic acid (WTA) biosynthesis inhibitors as combination agents to restore β-lactam efficacy against MRSA. Performing a whole-cell pathway-based screen, we identified a series of WTA inhibitors (WTAIs) targeting the WTA transporter protein, TarG. Whole-genome sequencing of WTAI-resistant isolates across two methicillin-resistant Staphylococci spp. revealed TarG as their common target, as well as a broad assortment of drug-resistant bypass mutants mapping to earlier steps of WTA biosynthesis. Extensive in vitro microbiological analysis and animal infection studies provide strong genetic and pharmacological evidence of the potential effectiveness of WTAIs as anti-MRSA β-lactam combination agents. This work also highlights the emerging role of whole-genome sequencing in antibiotic mode-of-action and resistance studies.

  7. Efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus: comparison with other oral antihyperglycaemic agents.

    Science.gov (United States)

    Derosa, Giuseppe

    2010-10-22

    Diabetes mellitus is a debilitating disease that is estimated to affect 366 million people by the year 2030. Type 2 diabetes mellitus (T2DM) is characterized by a progressive decline in pancreatic β-cell function and increased insulin resistance, and accounts for approximately 90% of people with diabetes. Oral antihyperglycaemic agents are extensively used in the treatment of T2DM. Thiazolidinediones are insulin sensitizers developed specifically for T2DM, which act via activation of peroxisome proliferator-activated receptors (PPARs). Pioglitazone is a thiazolidinedione that displays high affinity for PPARγ(1) and PPARγ(2), which are predominately expressed in adipose tissue. This review examines the published literature comparing the efficacy and tolerability of pioglitazone with other oral antihyperglycaemic agents in the treatment of patients with T2DM. Glycosylated haemoglobin, fasting glucose, insulin parameters and β-cell function are all improved with pioglitazone treatment, with efficacy similar to third-generation sulfonylureas, metformin and dipeptidyl peptidase-4 inhibitors. Pioglitazone reduces vascular risk and inflammatory markers, and improves carotid intima media thickness independent of its glycaemic effect. When compared with rosiglitazone, pioglitazone is associated with a reduction in the risk of hospitalization for acute myocardial infarction. Blood pressure is reduced and lipid profiles are favourably improved with pioglitazone; however, an increased risk for the development/exacerbation of heart failure, which is related to the increased incidence of oedema due to fluid retention, and fractures remain a concern. A low incidence of hypoglycaemia is observed with pioglitazone, especially compared with sulfonylureas. In conclusion, pioglitazone is an effective oral antihyperglycaemic agent with additional cardiovascular and lipid benefits that allows for the successful management of patients with T2DM.

  8. Antitumor activity of a combination of trastuzumab (Herceptin) and oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2-overexpressing pancreatic cancer.

    Science.gov (United States)

    Saeki, Hiroyuki; Yanoma, Shunsuke; Takemiya, Shouji; Sugimasa, Yukio; Akaike, Makoto; Yukawa, Norio; Rino, Yasushi; Imada, Toshio

    2007-08-01

    The cytotoxic effect of trastuzumab in combination with oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2 (HER2)-overexpressing human pancreatic cancer cell line TRG in vitro and in vivo was investigated. HER2 expression in TRG was analyzed by RT-PCR and flow cytometry. For in vitro experiments, 5-fluorouracil (5-FU) was used instead of S-1. In vivo studies were conducted with TRG xenografts in athymic mice. Trastuzumab (10 mg/kg) was administered intraperitoneally once a week for 4 weeks. S-1 (10 mg/kg) was administered orally 5 days a week for 4 weeks. The results showed that TRG cells were positive for HER2 mRNA and overexpressed HER2 protein. Either trastuzumab or 5-FU concentration-dependently inhibited the growth of TRG cells. The combination of trastuzumab and 5-FU resulted in a significant inhibition of growth of TRG cells compared to either agent alone (P<0.001). Incubation of TRG cells with peripheral blood mononuclear cells after treatment with trastuzumab enhanced the antiproliferative effect of trastuzumab, which could be the result of antibody-dependent cellular cytotoxicity. The combination of trastuzumab and S-1 resulted in a significant reduction in xenograft volume compared to each agent alone (P<0.0001). In conclusion, this study showed that combination therapy with trastuzumab and S-1 may be effective for HER2-overexpressing pancreatic cancer patients.

  9. 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.

  10. Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans

    OpenAIRE

    Cui, Jinhui; Ren, Biao; Tong, Yaojun; Dai, Huanqin; Zhang, Lixin

    2015-01-01

    Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of d...

  11. Optical clearing agent perfusion enhancement via combination of microneedle poration, heating and pneumatic pressure

    OpenAIRE

    Damestani, Y; Melakeberhan, B; Rao, MP; Aguilar, G.

    2014-01-01

    Background and Objective Optical clearing agents (OCAs) have shown promise for increasing the penetration depth of biomedical lasers by temporarily decreasing optical scattering within the skin. However, their translation to the clinic has been constrained by lack of practical means for effectively perfusing OCA within target tissues in vivo. The objective of this study was to address this limitation through combination of a variety of techniques to enhance OCA perfusion, including heating of...

  12. Multidrug Delivery Systems Based on Human Serum Albumin for Combination Therapy with Three Anticancer Agents.

    Science.gov (United States)

    Qi, Jinxu; Zhang, Yao; Gou, Yi; Lee, Philbert; Wang, Jun; Chen, Shifang; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong

    2016-09-06

    When administering several anticancer drugs within a single carrier, it is important to regulate their spatial distribution so as to avoid possible mutual interference and to thus enhance the drugs' selectivity and efficiency. To achieve this, we proposed to develop human serum albumin (HSA)-based multidrug delivery systems for combination anticancer therapy. We used three anticancer agents (an organic drug [5-fluorouracil, or 5FU], a metallic agent [2-benzoylpyridine thiosemicarbazide copper II, or BpT], and a gene agent [AS1411]) to treat liver cancer and confirm our hypothesis. The structure of the HSA-palmitic acid (PA)-5FU-BpT complex revealed that 5FU and BpT, respectively, bind to the IB and IIA subdomains of HSA. Our MALDI-TOF-MS spectral data show that one AS1411 molecule is conjugated to Cys-34 of the HSA-5FU-BpT complex via a linker. Compared with unregulated three-drug combination therapy, the HSA-5FU-BpT-AS1411 complex enhances cytotoxicity in Bel-7402 cells approximately 7-fold in vitro; however, in normal cells it does not raise cytotoxicity levels. Importantly, our in vivo results demonstrate that the HSA-5FU-BpT-AS1411 complex is superior to the unregulated three-drug combination in enhancing targeting ability, inhibiting liver tumor growth, and causing fewer side effects.

  13. Antibacterial properties of the Vietnamese cajeput oil and ocimum oil in combination with antibacterial agents.

    Science.gov (United States)

    Jedlicková, Z; Mottl, O; Serý, V

    1992-01-01

    Main antibacterially active agents obtained from plants-Cajeput essential oil--1,8 cineol, linalool, alpha-terpineol and terpinen-4-ol, for example from Melalleuce leucadendron (Myrtaceae) as well as essential oil from Ocimum gratissimum (Labiatae) were combined in tests in vitro with selected antibiotics. Above mentioned plant products were found to be effective medicaments for local application in modern medical practice. Combinations with antibiotics potentiated their therapeutical action. On the basis of tests in vitro the synergistic action of these two kinds of medicaments, i.e., preparations traditionally used for a few last decades--antibiotics--might be well applied for therapeutical needs.

  14. A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours.

    Science.gov (United States)

    Wilson, Richard H; Evans, Tr Jeffry; Middleton, Mark R; Molife, L Rhoda; Spicer, James; Dieras, Veronique; Roxburgh, Patricia; Giordano, Heidi; Jaw-Tsai, Sarah; Goble, Sandra; Plummer, Ruth

    2017-03-28

    This study evaluated safety, pharmacokinetics, and clinical activity of intravenous and oral rucaparib, a poly(ADP-ribose) polymerase inhibitor, combined with chemotherapy in patients with advanced solid tumours. Initially, patients received escalating doses of intravenous rucaparib combined with carboplatin, carboplatin/paclitaxel, cisplatin/pemetrexed, or epirubicin/cyclophosphamide. Subsequently, the study was amended to focus on oral rucaparib (once daily, days 1-14) combined with carboplatin (day 1) in 21-day cycles. Dose-limiting toxicities (DLTs) were assessed in cycle 1 and safety in all cycles. Eighty-five patients were enrolled (22 breast, 15 ovarian/peritoneal, and 48 other primary cancers), with a median of three prior therapies (range, 1-7). Neutropenia (27.1%) and thrombocytopenia (18.8%) were the most common grade ⩾3 toxicities across combinations and were DLTs with the oral rucaparib/carboplatin combination. Maximum tolerated dose for the combination was 240 mg per day oral rucaparib and carboplatin area under the curve 5 mg ml(-1) min(-1). Oral rucaparib demonstrated dose-proportional kinetics, a long half-life (≈17 h), and good bioavailability (36%). Pharmacokinetics were unchanged by carboplatin coadministration. The rucaparib/carboplatin combination had radiologic antitumour activity, primarily in BRCA1- or BRCA2-mutated breast and ovarian/peritoneal cancers. Oral rucaparib can be safely combined with a clinically relevant dose of carboplatin in patients with advanced solid tumours (Trial registration ID: NCT01009190).

  15. Impact of brief exposure to antifungal agents on the post-antifungal effect and hemolysin activity of oral Candida albicans

    Directory of Open Access Journals (Sweden)

    Arjuna Nishantha ELLEPOLA

    2015-08-01

    Full Text Available AbstractPost-antifungal effect (PAFE of Candida and its production of hemolysin are determinants of candidal pathogenicity. Candida albicans is the foremost aetiological agent of oral candidosis, which can be treated with polyene, azole, and echinocandin antifungals. However, once administered, the intraoral concentrations of these drugs tend to be subtherapeutic and transient due to the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intra-orally, Candidamay undergo a brief exposure to antifungal drugs.Objective Therefore, the PAFE and hemolysin production of oral C. albicans isolates following brief exposure to sublethal concentrations of the foregoing antifungals were evaluated.Material and Methods A total of 50 C. albicans oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to sublethal concentrations of nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole for 60 min. Thereafter, the drugs were removed and the PAFE and hemolysin production were determined by previously described turbidometric and plate assays, respectively.Results Nystatin, amphotericin B, caspofungin and ketoconazole induced mean PAFE (hours of 2.2, 2.18, 2.2 and 0.62, respectively. Fluconazole failed to produce a PAFE. Hemolysin production of these isolates was suppressed with a percentage reduction of 12.27, 13.47, 13.33, 8.53 and 4.93 following exposure to nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole, respectively.Conclusions Brief exposure to sublethal concentrations of antifungal drugs appears to exert an antifungal effect by interfering with the growth as well as hemolysin production of C. albicans.

  16. A Randomized, Controlled Trial to Assess the Efficacy of Arthroscopic Debridement in Combination with Oral Medication Versus Oral Medication in Patients with Gouty Knee Arthritis.

    Science.gov (United States)

    Wang, Xin; Wanyan, Pingping; Wang, Jian Min; Tian, Jin Hui; Hu, Long; Shen, Xi Ping; Yang, Ke Hu

    2015-12-01

    Gouty knee arthritis refers to a form of inflammatory diseases caused by deposits of needle-like crystals of uric acid in knee joint. The aim of this study was to assess the efficacy and safety of arthroscopic debridement in combination with oral medication versus oral medication alone for the treatment of gouty knee arthritis. A total of 60 patients with gouty knee arthritis were randomized to receive either arthroscopic surgery in combination with oral medication or oral medication alone. Efficacy was assessed with the angle of motion, functions, and visual analog scale (VAS). These indices were measured prior to treatment and at 2, 4, 12, 24, and 48 weeks posttreatment. Surgery- and medication-related complications were observed. Significant differences in flexion and extension of the knee joint, lymphoma scores, and VAS were detected between the two groups at 2, 4, and 12 weeks posttreatment (P  0.05) . Significant differences in these indices were detected at different time points in each group (P  0.05). Arthroscopic surgery in combination with oral medication is superior to single oral medication in the flexion and extension of the knee joint, lymphoma scores, and pain relief (VAS) before 24 weeks, although no statistical differences were detected in the efficacy after 24 weeks, and in medication-related safety between the two groups. Although arthroscopic debridement cannot replace systemic uric acid-lowering treatments such as medication and dietary control, it is still an effective approach.

  17. Deep vein thrombosis in a woman taking oral combined contraceptive pills.

    Science.gov (United States)

    Piparva, Kiran G; Buch, Jatin G

    2011-07-01

    Oral combined contraceptive pill (OCCP) is popular as birth control pills. Like all other drugs, they are not free from risks. Women taking certain types of OCCP have higher risk of developing deep vein thrombosis (DVT). A 29 year old married woman had taken OCCP for 3.5 months, developed deep vein thrombosis of left leg. Hereditary and acquired causes of DVT were excluded. She was treated with parenteral and oral anticoagulants simultaneously and was advised to discontinue OCCP. Initially the risk of blood clot was believed to be due to dose of estrogen but recent study relates it to the type of progesterone involved in OCCP. Thus, it is still a matter of debate, whether to associate risk of DVT to the amount of estrogen alone or also to the type of progestin. Apart from careful selection of patients, one should also look for the risk of venous thromboembolism irrespective of type of OCCP prescribed.

  18. 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.

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

    Science.gov (United States)

    Uehara, Masataka; Ohya, Ryouichi; Kodama, Masaaki; Shiraishi, Takeshi; Asahina, Izumi; Tominaga, Kazuhiro

    2015-01-01

    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.

  20. Deep vein thrombosis in a woman taking oral combined contraceptive pills

    Directory of Open Access Journals (Sweden)

    Kiran G Piparva

    2011-01-01

    Full Text Available Oral combined contraceptive pill (OCCP is popular as birth control pills. Like all other drugs, they are not free from risks. Women taking certain types of OCCP have higher risk of developing deep vein thrombosis (DVT. A 29 year old married woman had taken OCCP for 3.5 months, developed deep vein thrombosis of left leg. Hereditary and acquired causes of DVT were excluded. She was treated with parenteral and oral anticoagulants simultaneously and was advised to discontinue OCCP. Initially the risk of blood clot was believed to be due to dose of estrogen but recent study relates it to the type of progesterone involved in OCCP. Thus, it is still a matter of debate, whether to associate risk of DVT to the amount of estrogen alone or also to the type of progestin. Apart from careful selection of patients, one should also look for the risk of venous thromboembolism irrespective of type of OCCP prescribed.

  1. Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naive atrial fibrillation patients

    DEFF Research Database (Denmark)

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

    2015-01-01

    the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and another 20% were started on either rivaroxaban or apixaban. Rivaroxaban and apixaban users generally had a higher predicted risk of stroke and bleeding compared with warfarin and dabigatran users....... Older age, female gender, and prior stroke were some of the factors associated with NOAC use vs. warfarin, whereas chronic kidney disease, myocardial infarction, and heart failure showed the opposite association. CONCLUSION: Among oral anticoagulation-naïve AF patients initiated on oral anticoagulation...

  2. Dosage and Dose Schedule Screening of Drug Combinations in Agent-Based Models Reveals Hidden Synergies.

    Science.gov (United States)

    Barros de Andrade E Sousa, Lisa C; Kühn, Clemens; Tyc, Katarzyna M; Klipp, Edda

    2015-01-01

    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.

  3. 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.

  4. Management of Bleeding With Non-Vitamin K Antagonist Oral Anticoagulants in the Era of Specific Reversal Agents.

    Science.gov (United States)

    Ruff, Christian T; Giugliano, Robert P; Antman, Elliott M

    2016-07-19

    Vitamin K antagonists are commonly used by clinicians to provide anticoagulation to patients who have or are at risk of having thrombotic events. In addition to familiarity with the dosing and monitoring of vitamin K antagonists, clinicians are accustomed to using vitamin K if there is a need to reverse the anticoagulant effect of vitamin K antagonists. There are now 4 new non-vitamin K antagonist oral anticoagulants (NOACs) that are attractive alternatives to vitamin K antagonists. Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur with NOACs and to reverse the pharmacological effect of these agents if needed. Important steps in minimizing bleeding risks with NOACs include dose adjustment of the agents in the setting of renal dysfunction and avoidance of the concomitant use of other antithrombotic agents if feasible. Laboratory measurement of the anticoagulant effect of NOACs is best accomplished with specialized assays, although some of the more widely available coagulation tests can provide information that is potentially useful to clinicians. Nonspecific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa can be used to reverse the effect of NOACs. More specific reversing agents include the approved humanized monoclonal antibody fragment idarucizumab for reversing the effects of dabigatran, the investigational factor Xa decoy andexanet alfa, and the synthetic small molecule ciraparantag. Both andexanet and ciraparantag have been reported to reverse the effects of the anti-Xa NOACs (rivaroxaban, apixaban, and edoxaban), and a number of other anticoagulant agents in common clinical use, as well.

  5. 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.

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

    Science.gov (United States)

    Dasgupta, Tina; Haas-Kogan, Daphne A

    2013-01-01

    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 pediatric gliomas is being exploited with the use of specific targeted inhibitors. These agents are additionally being combined with XRT to increase the efficacy and duration of local control. In this review, we discuss novel agents targeting three different pathways in gliomas, and their potential combination with XRT. BRAF is a serine/threonine kinase in the RAS/RAF/MAPK kinase pathway, which is integral to cellular division, survival, and metabolism. Two-thirds of pilocytic astrocytomas, a low-grade pediatric glioma, contain a translocation within the BRAF gene called KIAA1549:BRAF that causes an overactivation of the MEK/MAPK signaling cascade. In vitro and in vivo data support the use of MEK or mammalian target of rapamycin (mTOR) inhibitors in low-grade gliomas expressing this translocation. Additionally, 15-20% of high-grade pediatric gliomas express BRAF V600E, an activating mutation of the BRAF gene. Pre-clinical in vivo and in vitro data in BRAF V600E gliomas demonstrate dramatic cooperation between XRT and small molecule inhibitors of BRAF V600E. Another major signaling cascade that plays a role in pediatric glioma pathogenesis is the PI3-kinase (PI3K)/mTOR pathway, known to be upregulated in the majority of high- and low-grade pediatric gliomas. Dual PI3K/mTOR inhibitors are in clinical trials for adult high-grade gliomas and are poised to enter studies of pediatric tumors. Finally, many brain tumors express potent stimulators of angiogenesis that render them refractory to treatment. An analog of thalidomide, CC-5103 increases the secretion of critical cytokines of the tumor

  7. Imaging liver metastases with a new oral manganese-based contrast agent.

    NARCIS (Netherlands)

    Chabanova, E.; Logager, V.; Moller, J.M.; Dekker, H.M.; Barentsz, J.O.; Thomsen, H.S.

    2006-01-01

    RATIONALE AND OBJECTIVES: The purpose of the study was a preliminary evaluation of a new oral, manganese-based, liver-specific contrast medium (CMC-001; CMC Contrast AB, Malmoe, Sweden) for magnetic resonance imaging (MRI) in patients with liver metastases. MATERIALS AND METHODS: The study included

  8. Imaging liver metastases with a new oral manganese-based contrast agent.

    NARCIS (Netherlands)

    Chabanova, E.; Logager, V.; Moller, J.M.; Dekker, H.M.; Barentsz, J.O.; Thomsen, H.S.

    2006-01-01

    RATIONALE AND OBJECTIVES: The purpose of the study was a preliminary evaluation of a new oral, manganese-based, liver-specific contrast medium (CMC-001; CMC Contrast AB, Malmoe, Sweden) for magnetic resonance imaging (MRI) in patients with liver metastases. MATERIALS AND METHODS: The study included

  9. Fabrication and evaluation of oral tablets using natural mucoadhesive agent from seeds of Caesalpinia pulcherrima (L. SW

    Directory of Open Access Journals (Sweden)

    Jeevanandham S

    2010-01-01

    Full Text Available Oral mucoadhesive sustained drug delivery systems of salbutamol sulfate were formulated using an isolated natural agent from the seeds of Caesalpinia pulcherrima. The isolated material was evaluated for various parameters, such as, melting point, viscosity, pH, elemental analysis, swelling index, phytochemical constituents, and solubility studies. The mucoadhesive characters of the isolated substance were identified by a comparative study with hydroxyl propyl cellulose and sodium alginate, by various in vitro methods, such as, Shear stress measurement, Wilhelmy′s method, Falling sphere method, and Detachment force measurement. Formulation and evaluation of mucoadhesive oral tablets of salbutamol sulfate (100 mg, using isolated natural materials in different proportions, and in vitro release studies, were carried out for three different formulations according to the U.S.P apparatus two (paddle method. Each 100 mg tablet was taken in 900 ml of acid buffer 1.2 and maintained at 37˚C. After two hours the filtrate was collected and replaced in buffer 7.4. In vitro releases of three different formulations for nine hours were studied, which showed the sustained action of drug release with increasing the concentration of the isolated natural mucoadhesive agent in the formulations.

  10. ORMELOXIFEN HCL VS. COMBINED ORAL CONTRACEPTIVE PILL IN TREATMENT OF DUB

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    Veena

    2014-01-01

    Full Text Available INTRODUCTION : DUB is defined as a state of abnormal uterine bleeding without any clinically detectable organic pelvic pathology - tumor , inflammation or pregnancy. The present study was conducted to compare the effect of ormeloxifene HCL ( SERM and combined oral contraceptive pills in medical treatment of DUB. MATERIAL & METHOD: This study is based on 100 cases of DUB from age group of 20 to 50 years , out of which fifty cases were prescribed Ormeloxifen HCL (Drug A and another 50 cases were given Combined Contrac eptive pills. (Drug B Ormeloxifen HCL was given in doses of 60mg biweekly for 12 weeks and from 13 th week one tablet weekly for another 12 weeks. CC pills (Levonorgestrel 0.15mg & Ethinyloestradiol 0.03mg – One tablet from 5th day of menses for 21 days g iven cyclically for six months. Regular cyclic follow - up was done to assess response , compliance tolerance and recurrence of the symptoms and side effects of every patient. RESULT : The study revealed marked decrease in PBAC score 82% vs. 35% , reduction in percentage of bleeding 100%vs 68% , regularization of menstrual cycle100%vs74% , recurrence of symptoms in the form of excessive bleeding 4% vs. 64% and irregular cycle 0%vs 68% in drug A vs. drug B and side effects were comparable in both the groups. CONCL USION : Ormeloxifen HCL is more effective , well tolerated with superior compliance than combined oral contraceptive pills in medical treatment of DUB.

  11. [Effect of combined hormonal oral contraception on the somatic and psychic status of women of reproductive age].

    Science.gov (United States)

    Vertkin, A L; Nosova, A V

    2012-01-01

    The paper is devoted to the topical problem of maintaining somatic and psychic health of the women of reproductive age by rational pregnancy planning and prevention of abortions by modern methods of contraception including combined oral hormonal contraception. Unfortunately, this approach is rarely employed in this country (5-6%). Results of retrospective analysis of medical documentation, clinical efficacy and safety of modern combined oral hormonal contraception are presented.

  12. 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....

  13. Noncontraceptive benefits of the estradiol valerate/dienogest combined oral contraceptive: a review of the literature

    Directory of Open Access Journals (Sweden)

    Nappi RE

    2014-08-01

    Full Text Available Rossella E Nappi,1 Marco Serrani,2 Jeffrey T Jensen3 1Department of Obstetrics and Gynecology, Research Centre for Reproductive Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy; 2Global Medical Affairs Women's Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany; 3Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA Abstract: Combined oral contraceptives formulated to include estradiol (E2 have recently become available for the indication of pregnancy prevention. A combined estradiol valerate and dienogest pill (E2V/DNG, designed to be administered using an estrogen step-down and a progestin step-up regimen over 26 days of active treatment followed by 2 days of placebo (26/2-day regimen, has also undergone research to assess the potential for additional noncontraceptive benefits. Randomized, placebo-controlled studies have demonstrated that E2V/DNG is an effective treatment for heavy menstrual bleeding – a reduction in median menstrual blood loss approaching 90% occurs after 6 months of treatment. To date, E2V/DNG is the only oral contraceptive approved for this indication. Comparator studies have also demonstrated a reduction in hormone withdrawal-associated symptoms in users of E2V/DNG compared with a conventional 21/7-day regimen of ethinylestradiol/levonorgestrel. Other potential noncontraceptive benefits associated with E2V/DNG, like improvement in dysmenorrhea, sexual function, and quality of life, are comparable with those associated with other combined oral contraceptives and are discussed further in this review. Keywords: heavy menstrual bleeding, hormone withdrawal-associated symptoms, quality of life

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

    Science.gov (United States)

    Oghabian, Zohreh; Mehrpour, Omid

    2016-01-01

    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-year-old 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. PMID:27606117

  15. 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.

  16. Serum Level and 24hr. Excretion Pattern of Potassium Following the Intake of Combined Oral Contraceptives

    Directory of Open Access Journals (Sweden)

    S. Kamyab

    1978-01-01

    Full Text Available Serum level and 24hr urinary excretion pattern of potassium have been studied in 104 healthy women, aged 18-44 years, using combinedoral contraceptives for a period of 3-48 months, and results h av e been compared with those obtained from 21 healthy controls of the same clinic. aged 19-40 years, using IUD. There was no sign ificant change observed in s erum potassium level, but 24hr urinary excretion pattern of potassium decreased significantly in 90% of the individuals equivalent to 2. &- 78 . 3% of the mean control, possibly due to a retention of potas sium in the cells.

  17. Preclinical Investigations of PM01183 (Lurbinectedin as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary.

    Directory of Open Access Journals (Sweden)

    Ryoko Takahashi

    Full Text Available The objective of this study was to evaluate the antitumor effects of lurbinectedin as a single agent or in combination with existing anticancer agents for clear cell carcinoma (CCC of the ovary, which is regarded as an aggressive, chemoresistant, histological subtype.Using human ovarian CCC cell lines, the antitumor effects of lurbinectedin, SN-38, doxorubicin, cisplatin, and paclitaxel as single agents were assessed using the MTS assay. Then, the antitumor effects of combination therapies involving lurbinectedin and 1 of the other 4 agents were evaluated using isobologram analysis to examine whether these combinations displayed synergistic effects. The antitumor activity of each treatment was also examined using cisplatin-resistant and paclitaxel-resistant CCC sublines. Finally, we determined the effects of mTORC1 inhibition on the antitumor activity of lurbinectedin-based chemotherapy.Lurbinectedin exhibited significant antitumor activity toward chemosensitive and chemoresistant CCC cells in vitro. An examination of mouse CCC cell xenografts revealed that lurbinectedin significantly inhibits tumor growth. Among the tested combinations, lurbinectedin plus SN-38 resulted in a significant synergistic effect. This combination also had strong synergistic effects on both the cisplatin-resistant and paclitaxel-resistant CCC cell lines. Everolimus significantly enhanced the antitumor activity of lurbinectedin-based chemotherapies.Lurbinectedin, a new agent that targets active transcription, exhibits antitumor activity in CCC when used as a single agent and has synergistic antitumor effects when combined with irinotecan. Our results indicate that lurbinectedin is a promising agent for treating ovarian CCC, both as a first-line treatment and as a salvage treatment for recurrent lesions that develop after platinum-based or paclitaxel treatment.

  18. Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and oral administration in goats.

    Science.gov (United States)

    Carceles, C M; Escudero, E; Vicente, M S; Serrano, J M; Carli, S

    1995-12-01

    The intravenous and oral pharmacokinetics of an amoxicillin and clavulanic acid combination (20 mg/kg of sodium amoxicillin and 5 mg/kg of potassium clavulanate) were studied in six goats. After intravenous administration the pharmacokinetics of both drugs could be described by an open two-compartment model. Amoxicillin had a greater distribution volume (0.19 +/- 0.01 l/kg) than clavulanic acid (0.15 +/- 0.01 l/kg), whereas the distribution and elimination constants were higher for the latter, which was eliminated more quickly than amoxicillin. After oral administration of both drugs their pharmacokinetic behaviour was best described by an open one-compartment model with first-order absorption. Elimination half-lives were twice as long after oral (2.15 +/- 0.20 h and 1.94 +/- 0.16 h for amoxicillin and clavulanic acid respectively) than after intravenous administration (1.20 +/- 0.16 h and 0.86 +/- 0.09, respectively). An apparent 'flip-flop' situation was evident in this study. Bioavailability was 27% for amoxicillin and 50% for clavulanic acid.

  19. 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

  20. Renal cell carcinoma: review of novel single-agent therapeutics and combination regimens.

    Science.gov (United States)

    Amato, R J

    2005-01-01

    A search of the Medline database and ASCO 2003 conference proceedings was conducted to identify clinical trials currently underway using single-agent therapy for renal cell carcinoma (RCC). Combination trials were identified using the ASCO 2003 conference proceedings. Fourteen single-agent therapies employing different mechanisms of action were identified in the published literature: imatinib mesylate (Gleevec); bevacizumab (Avastin); thalidomide (Thalomid); gefitinib (ZD1839) (Iressa); cetuximab (IMC-C225) (Erbitux); bortezomib (PS-341) (Velcade); HSPPC-96 (Oncophage); BAY 59-8862; ABT-510; G250; CCI-779; SU5416; PTK/ZK; and ABX-EGF. Six distinct fields of clinical research have emerged: monoclonal antibodies, small molecules, vaccines, second-generation taxanes, nonapeptides and immunomodulators. Five combination regimens, primarily biological response modifiers (interleukin-2 or interferon-alpha), chemotherapy- or thalidomide-based, were identified. All therapies demonstrated acceptable toxicity profiles. Clinical benefit was assessed based on each study's reported criteria: antitumor response (regression or stability) ranged from 5% to 71%. In the past several years, significant advances in the underlying biological mechanisms of RCC, particularly the role of tumor angiogenesis, have permitted the design of molecularly targeted therapeutics. Based on preliminary and limited studies, combination therapies offer the greatest clinical benefit in the management of this malignancy, although additional basic research is still warranted.

  1. Oral distension methods for small bowel MRI: comparison of different agents to optimize bowel distension.

    Science.gov (United States)

    Schmidt, Stefan A; Baumann, Julia A; Stanescu-Siegmund, Nora; Froehlich, Eckhart; Brambs, Hans-Juergen; Juchems, Markus S

    2016-12-01

    Background Different methods for bowel distension prior to magnetic resonance imaging (MRI) examinations were described in recent years. Purpose To compare orally administered psyllium or locust bean gum / mannitol (LBM) with tylose administered through a duodenal catheter for bowel distension in patients undergoing MRI examination of the small bowel. Material and Methods Three different methods of bowel distension prior to MRI were compared: tylose applied through a duodenal catheter and orally administered psyllium and LBM in three groups with 15 patients each. Datasets were blinded and reviewed independently by two experienced radiologists, who assessed the diagnostic value and the maximum luminal diameter. Results Tylose was superior to psyllium and LBM in the examination of the duodenum and proximal jejunum. LBM was superior to the other methods for distension of the ileum and terminal ileum. The greatest luminal diameter of the duodenum was achieved after tylose and distension of the terminal ileum was the best in patients receiving LBM. The psyllium group was inferior to the other two groups in all segments. Conclusion By using LBM as an oral method of bowel distension, many patients can avoid the unpleasant placement of a duodenal catheter without compromising the diagnostic value of the examination.

  2. Improving adherence with oral antiemetic agents in patients with breast cancer receiving chemotherapy.

    Science.gov (United States)

    Hendricks, Carolyn B

    2015-05-01

    In this small breast cancer-dedicated solo practice, a retrospective medical record review disclosed the following: significant rate of chemotherapy-related nausea and vomiting and discordance between patient-reported compliance with prescribed antiemetics and medical record documentation of compliance. As part of the curriculum for the American Society of Clinical Oncology (ASCO) Quality Training Program, a quality improvement project was developed to improve adherence to oral antiemetics in our patients with breast cancer receiving highly emetogenic chemotherapy. The following steps were undertaken in plan-do-study-act cycles to improve adherence: enhanced patient education at time of chemotherapy consent, implementation of standardized in-person or e-mail contact with our patients receiving chemotherapy, and improvement of our electronic health record documentation of adherence to oral antiemetics. A run chart was generated to analyze our data. After our interventions, the percentage of patients who took their antiemetics as prescribed rose from a baseline of 49% to 79%. Significant improvement in adherence to oral antiemetics among patients with breast cancer receiving chemotherapy was achieved and sustained in this small-practice setting using the framework provided by participation in the ASCO Quality Training Program. Copyright © 2015 by American Society of Clinical Oncology.

  3. Adherence to oral antineoplastic agents by cancer patients: definition and literature review.

    Science.gov (United States)

    Bassan, F; Peter, F; Houbre, B; Brennstuhl, M J; Costantini, M; Speyer, E; Tarquinio, C

    2014-01-01

    Since the 1990s, oral chemotherapy has been gaining ground as cancer treatment. This therapy seems to have few toxic effects and offers patients good quality of life. However, in addition to the fears the therapy might generate in patients, oral treatment raises a new issue, which, until now, has been marginal in this field: therapeutic observance or adherence. We investigated the research into adherence to oral chemotherapy among cancer patients published between 1990 and July 2013. Studies showed considerable diversity in terms of both the definition and measurement of adherence. As well, adherence to antineoplastic therapy is affected by the patient's understanding of the treatment and ability to remember information provided by the physician, treatment length and psychological distress. Our review of the few studies on adherence to anticancer drug treatment raises some questions that could be pursued in future research. In light of our findings, patients should receive 'therapy education' to help them and their support groups better understand the disease and its treatment and to achieve optimal health management and improved treatment effectiveness. © 2013 John Wiley & Sons Ltd.

  4. 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

  5. [Clinical experience of combined oral contraceptives of low doses in Mexico].

    Science.gov (United States)

    Saldívar Rodríguez, Donato; Vázquez, Juanita; Lara, Roger; Ramos, Carlos; Lira, Josefina; Rodríguez, Ever; Romo, Jorge

    2006-11-01

    The combined oral contraceptives are one of the most prescribed medicines. Across the years they have given to more than 60 million women of the whole world a suitable method for the highly reliable and effective natal control. The oral contraceptives are different from other medicines; principally they are not in use for controlling any disease and have the potential of giving advantages. To evaluate the control of the cycle, tolerability and acceptance of an oral contraceptive of ultralow dose with gestodene (60 microg) and ethinylestradiol (15 microg) in a population of healthy women from 18 to 35 years. The study included adult healthy women, all the users signed assent of informed before being included to the study and of the beginning of any procedure in agreement with the declarations of Helsinki and its amendments. Descriptive statistics was used for the demographic information and the comparison between the initial and final visits of the variables of efficiency. There was used the test (Proof) of ranges of Wilcoxon's sign for related samples. There were included 113 women. The average of age was 26.08 years (SD = 4.43), weight of 62.02 kg (SD = 11.13) and height of 159.20 cm (SD = 6.06). The distribution in four centers was: 32 in the University Hospital (Monterrey), 21 in the Country 2000 (Guadalajara), 30 in in the Medical Center La Mora (Aguascalientes) and 30 in Perinatology National Institute (Mexico City). The contraceptive efficiency of the combination of 15 microg of ethinylestradiol and 60 microg of gestodene has been demonstrated in previous studies. This study ratifies the international results of efficiency and tolerability.

  6. Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia.

    Science.gov (United States)

    Xie, Qi; Zhang, Han-Fang; Guo, Ying-Zi; Wang, Peng-Yi; Liu, Zhong-Shung; Gao, Hua-Dong; Xie, Wei-Li

    2015-04-01

    Cancer cells preferentially catalyze glucose through the glycolytic pathway in the presence of adequate oxygen. This phenomenon is known as the Warburg effect. As is the case with numerous cancer therapeutic agents, resistance remains a significant problem when using Taxol® to treat malignancies. The present study reported that expression of pyruvate dehydrogenase kinase 1 (PDK1) was induced by Taxol treatment at low toxic concentrations in oral cancer cells. In addition, Taxol‑resistant cells exhibited upregulated PDK1 protein and mRNA expression. Elevated PDK1 levels contribute to Taxol resistance under hypoxic conditions. Inhibition of PDK1 expression was observed when oral cancer cells were treated with the PDK1 inhibitor dichloroacetate (DCA). The combination of Taxol with DCA showed synergistic inhibitory effects on Taxol‑resistant cells under hypoxic conditions; these effects were not observed in Taxol‑sensitive oral cancer cells under normoxic conditions. The present study provides a novel mechanism for overcoming Taxol resistance in oral cancer cells, and will contribute towards the development of clinical therapeutics for cancer patients.

  7. Tailoring controlled-release oral dosage forms by combining inkjet and flexographic printing techniques

    DEFF Research Database (Denmark)

    Genina, Natalja; Fors, Daniela; Vakili, Hossein;

    2012-01-01

    We combined conventional inkjet printing technology with flexographic printing to fabricate drug delivery systems with accurate doses and tailored drug release. Riboflavin sodium phosphate (RSP) and propranolol hydrochloride (PH) were used as water-soluble model drugs. Three different paper...... substrates: A (uncoated woodfree paper), B (triple-coated inkjet paper) and C (double-coated sheet fed offset paper) were used as porous model carriers for drug delivery. Active pharmaceutical ingredient (API) containing solutions were printed onto 1 cm × 1 cm substrate areas using an inkjet printer...... showed excellent content uniformity. So, combining the two printing technologies allowed fabricating controlled-release oral dosage forms that are challenging to produce using a single technique. The approach opens up new perspectives in the manufacture of flexible doses and tailored drug...

  8. The evolution of combined oral contraception: improving the risk-to-benefit ratio.

    Science.gov (United States)

    Burkman, Ronald; Bell, Carrie; Serfaty, David

    2011-07-01

    Since its introduction in 1960, the combined oral contraceptive (COC) pill has become one of the most widely and frequently used methods of contraception worldwide. Although highly effective, early COC formulations were associated with significant adverse effects and unacceptable cardiovascular risk. Improvements in tolerability and safety have been achieved, without compromises in effectiveness, primarily via hormone dosage reductions and the development of several new progestins. Multiphasic COCs and extended-/continuous-cycle COCs have also been introduced, although the clinical advantages of these formulations vs. traditional COCs have yet to be established. Inclusion of natural estrogens such as estradiol valerate and 17β-estradiol with selective progestins in new combinations that maintain good cycle control is the most recent evolutionary step designed to improve COC tolerability and safety. Vigorous research needs to continue to help guarantee that the unmet need for safe and effective contraception is satisfied in future generations.

  9. Hemolysis after Oral Artemisinin Combination Therapy for Uncomplicated Plasmodium falciparum Malaria

    Science.gov (United States)

    Lingscheid, Tilman; Steiner, Florian; Stegemann, Miriam S.; Bélard, Sabine; Menner, Nikolai; Pongratz, Peter; Kim, Johanna; von Bernuth, Horst; Mayer, Beate; Damm, Georg; Seehofer, Daniel; Salama, Abdulgabar; Suttorp, Norbert; Zoller, Thomas

    2016-01-01

    Episodes of delayed hemolysis 2–6 weeks after treatment of severe malaria with intravenous artesunate have been described. We performed a prospective observational study of patients with uncomplicated malaria to investigate whether posttreatment hemolysis also occurs after oral artemisinin-based combination therapy. Eight of 20 patients with uncomplicated malaria who were given oral artemisinin-based combination therapy met the definition of posttreatment hemolysis (low haptoglobin level and increased lactate dehydrogenase level on day 14). Five patients had hemolysis persisting for 1 month. Patients with posttreatment hemolysis had a median decrease in hemoglobin level of 1.3 g/dL (interquartile range 0.3–2.0 g/dL) in the posttreatment period, and patients without posttreatment hemolysis had a median increase of 0.3 g/dL (IQR −0.1 to 0.7 g/dL; p = 0.002). These findings indicate a need for increased vigilance for hemolytic events in malaria patients, particularly those with predisposing factors for anemia. PMID:27434054

  10. Preoperative simultaneous combined radiotherapy and chemotherapy with mainly composed of CDDP in oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kirita, Tadaaki; Tsuyuki, Motokatsu; Ohgi, Kazuhiko; Kamibayashi, Toyohiko; Horiuchi, Keisuke; Horiuchi, Katsuhiro; Sugimura, Masahito [Nara Medical Univ., Kashihara (Japan)

    1995-03-01

    Thirty-six patients with squamous cell carcinoma of the oral region were treated preoperatively with CDDP (15 mg/m{sup 2} x 3 days), PEP (5 mg/body x 4 days) or CBDCA (70-100 mg/m{sup 2} x 3 days), 5FU (500-750 mg/body x 4 days) in combination with simultaneous radiation (30-40 Gy). Thirty-three patients (91.2%) had Stage III or IV carcinomas whereas 3 patients had Stage II lesions. The clinical response was vary encouraging: 22 patients (61.1%) achieved CR, 13 patients (36.1%) were judged as PR, only one patient (2.8%) was NC, and overall response rates were 97.2%. Histological effects were seen in 33/36 (91.7%) (9 as Grade IIB, 8 as Grade III, 16 as Grade IV according to Shimosato`s classification.) and especially 72.7% of CR were histologically negative for tumor. Side effects of this therapy were minimal and reversible. With a follow-up ranging from 8-76 months, 5-year cumulative survival rates are 81.5% for all patients, and 100% as Stage II, 87.4% as Stage III, 72.8% as Stage IV, respectively. Morbidity after subsequent curative surgery is none, and histologic complete response are frequent. This preoperative combined simultaneous chemoradiotherapy appeares a highly active and well tolerated regimen for even advanced and highly malignant carcinomas of the oral cavity. (author).

  11. Serum resistin levels in women taking combined oral contraceptives containing desogestrel or gestodene.

    Science.gov (United States)

    Rechberger, Tomasz; Tomaszewski, Jacek; Pieprzowska-Białek, Anna; Kulik-Rechberger, Beata; Skorupski, Paweł

    2004-06-01

    Resistin is a hormone secreted by adipose tissue that could be involved in the development of insulin resistance. Previous studies confirmed that endogenous sex steroids may influence serum resistin concentration in women. The aim of our study was to investigate the influence of combined oral contraceptives containing desogestrel or gestodene on circulating levels of resistin. Fifty-three women were enrolled in the study. Thirteen patients received 20 microg ethinylestradiol/150 microg desogestrel, 15 women were treated with 20 microg ethinylestradiol/75 microg gestodene, 11 with 30 microg ethinylestradiol/150 microg desogestrel and 14 with 30 microg ethinylestradiol/75 microg gestodene. Blood samples for estimation of serum resistin and insulin levels were drawn before administration of oral contraceptive and after 6 cycles of therapy. We found that serum resistin level remained unchanged in women receiving ethinylestradiol/desogestrel and was reduced in women treated with formulations containing gestodene. We conclude that ethinylestradiol combined with desogestrel or gestodene is unlikely to induce insulin resistance through resistin pathway.

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

    Directory of Open Access Journals (Sweden)

    Wisam Alhamadi

    2017-01-01

    Full Text Available Background. 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. Methods. 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. Results. According to bliss independent interaction, the synergistic interactions depended on ΔE values that showed the best for CIP was with AMB (ΔE=55.14 followed with KET (ΔE=41.23 and lastly ITR (ΔE=39.67 at CIP = 150 mg/L. DOX was optimal with KET (ΔE=42.11 followed with AMB (ΔE=40.77 and the lowest with ITR (ΔE=9.12 at DOX = 75 mg/L. MET is the best with AMB (ΔE=40.95 and then with ITR (ΔE=35.45 and finally KET (ΔE=15.15 at MET 200 mg/L. Moreover, usage of higher concentrations of antibacterial agents revealed inhibitory effects. Conclusion. This study uncovers the optimum antibiotic combination therapy against cariogenic candida with FOA by usage of low therapeutic concentrations.

  13. Combination of chemotherapy and cancer stem cell targeting agents: Preclinical and clinical studies.

    Science.gov (United States)

    Li, Yanyan; Atkinson, Katharine; Zhang, Tao

    2017-06-28

    The cancer stem cell model claims that the initiation, maintenance, and growth of a tumor are driven by a small population of cancer cells termed cancer stem cells. Cancer stem cells possess a variety of phenotypes associated with therapeutic resistance and often cause recurrence of the diseases. Several strategies have been investigated to target cancer stem cells in a variety of cancers, such as blocking one or more self-renewal signaling pathways, reducing the expression of drug efflux and ATP-binding cassette efflux transporters, modulating epigenetic aberrations, and promoting cancer stem cell differentiation. A number of cell and animal studies strongly support the potential benefits of combining chemotherapeutic drugs with cancer stem cell targeting agents. Clinical trials are still underway to address the pharmacokinetics, safety, and efficacy of combination treatment. This mini-review provides an updated discussion of these preclinical and clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Clinical trial success rates of anti-obesity agents: the importance of combination therapies.

    Science.gov (United States)

    Hussain, H T; Parker, J L; Sharma, A M

    2015-09-01

    The objective of this study was to construct a clinical trial profile assessing the risk of drug failure among anti-obesity agents. Research was conducted by looking at anti-obesity therapies currently on the market or in clinical trials (phases I to III) conducted from 1998 to September 2014, with the exclusion of any drugs whose phase I trial was conducted prior to January 1998. This was completed primarily through a search on http://clinicaltrials.gov where a total of 51 drugs met the search criteria. The transition probabilities were then calculated based on various classifications and compared against industry standards. The transition probability of anti-obesity agents was 8.50% whereas the transition probability of industry standards was 10.40%. Combination therapies had four times the transition probability than monotherapies, 40% and 4.75%, respectively. Therefore, it was determined that 92% of drugs fail during clinical trial testing for this indication and combination therapy appears to improve clinical trial success rates to 10-fold. © 2015 World Obesity.

  15. 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.

  16. Treatment of cancer using pulsed electric field in combination with chemotherapeutic agents or genes.

    Science.gov (United States)

    Nishi, T; Dev, S B; Yoshizato, K; Kuratsu, J; Ushio, Y

    1997-03-01

    Electroporation is a standard laboratory technique originally developed for in vitro transfer of molecules into cells. It involves application of electrical pulses ranging from micro- to milliseconds that create transient pores in the cell membrane allowing intracellular access of exogenous molecules. This technique has been successfully applied to regress tumors in animal models by combining electroporation with chemotherapeutic agents--a process known as electrochemotherapy (ECT) which substantially enhance cytotoxicity of some antineoplastic agents. Recently ECT has moved into clinical arena and patients with cutaneous tumors and head and neck cancers have been treated very effectively with ECT. Parallel to ECT, a technique has also been developed which makes it possible to inject plasmid DNA and combine it with in vivo electroporation--electro--genetherapy (EGT)--to deliver in a highly efficient manner both marker and functional genes into target tissue and achieve gene expression. Thus, in vivo electroporation is contributing to the development of a new strategy for cancer treatment with both drugs and genes.

  17. Influence of dental exposure to oral environment on smear layer removal and collagen exhibition after using different conditioning agents.

    Science.gov (United States)

    Fontanari, Lucas Amaral; Pinto, Shelon Cristina Souza; Cavassim, Rodrigo; Spin-Neto, Rubens; Ishi, Eduardo de Paula; Sampaio, José Eduardo Cezar

    2011-01-01

    Although in vitro studies have shown encouraging results for root surface conditioning with demineralizing agents, in vivo studies have failed to show its benefits in periodontal healing. This can be attributed to several factors, among which, the hypermineralization of dental surface. Therefore, this in vitro study compared, using scanning electron microscopy (SEM), the effect of root surface conditioning with different conditioners (1% and 25% citric acid, 24% EDTA and 50 mg/mL tetracycline hydrochloride) in impacted teeth and in teeth that had their roots exposed to the oral environment. One trained examiner assessed the SEM micrographs using a root surface modification index. There was a tendency of more root surface modification in the group of impacted teeth, suggesting that the degree of root mineralization influences its chemical demineralization.

  18. 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

  19. Combination of a sterol absorption inhibitor and cardiovascular agents for the treatment of dyslipidemia.

    Science.gov (United States)

    Chrysohoou, Christina; Singh, Steven

    2006-01-01

    Although statins are effective in reducing cardiovascular risk, combination therapy may be required to meet recommended target LDL-C levels. However, the utility of current combination therapies with niacin or bile acid sequestrants is limited by side effects and compliance. Ezetimibe, as a selective cholesterol absorption inhibitor, represent a new class of pharmaceutical agents. The combination of ezetimibe with statins has shown a 16-21% increase in the percentage of patients achieving their ATP III LDL-C goal. Randomized, double-blind studies have shown that coadministration of ezetimibe with simvastatin is well tolerated, causing dose-dependent reduction in LDL-C and total cholesterol levels, with no apparent effect on high-density lipoprotein cholesterol or triglycerides. Even in diabetes mellitus type 2 patients; the addition of ezetimibe 10 mg to simvastatin 20 mg is more efficacious than doubling the dose of simvastatin in lowering lipid parameters. Similarly the coadministration of ezetimibe and rosuvastatin, has shown a mean incremental reduction in LDL-C of -16%, compared with rosuvastatin alone, while there was no apparent effect on HDL-C or triglycerides. Ezetimibe and fenofibrate co-administration has shown also improvement in the lipid/lipoprotein profile. The combination therapy with ezetimibe and statin or fibrate may be an effective therapeutic option for patients with dyslipidemia.

  20. Topical polyethylene glycol as a novel chemopreventive agent for oral cancer via targeting of epidermal growth factor response.

    Directory of Open Access Journals (Sweden)

    Ramesh K Wali

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1-oxide rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21(cip1/waf1. In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Neha Agrawal

    2015-01-01

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

  3. Abiotic reductive extraction of arsenic from contaminated soils enhanced by complexation: Arsenic extraction by reducing agents and combination of reducing and chelating agents

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Jung [Department of Bioactive Material Sciences, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeollabukdo 561-675 (Korea, Republic of); Lee, Jae-Cheol [Department of Environmental Engineering, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeollabukdo 561-675 (Korea, Republic of); Baek, Kitae, E-mail: kbaek@jbnu.ac.kr [Department of Bioactive Material Sciences, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeollabukdo 561-675 (Korea, Republic of); Department of Environmental Engineering, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeollabukdo 561-675 (Korea, Republic of)

    2015-02-11

    Highlights: • Abiotic reductive extraction of As from contaminated soils was studied. • Oxalate/ascorbate were effective in extracting As bound to amorphous iron oxides. • Reducing agents were not effective in extracting As bound to crystalline oxides. • Reductive As extraction was greatly enhanced by complexation. • Combination of dithionite and EDTA could extract about 90% of the total As. - Abstract: Abiotic reductive extraction of arsenic from contaminated soils was studied with various reducing agents and combinations of reducing and chelating agents in order to remediate arsenic-contaminated soils. Oxalate and ascorbic acid were effective to extract arsenic from soil in which arsenic was associated with amorphous iron oxides, but they were not effective to extract arsenic from soils in which arsenic was bound to crystalline oxides or those in which arsenic was mainly present as a scorodite phase. An X-ray photoelectron spectroscopy study showed that iron oxides present in soils were transformed to Fe(II,III) or Fe(II) oxide forms such as magnetite (Fe{sub 3}O{sub 4}, Fe{sup II}Fe{sub 2}{sup III}O{sub 4}) by reduction with dithionite. Thus, arsenic extraction by dithionite was not effective due to the re-adsorption of arsenic to the newly formed iron oxide phase. Combination of chelating agents with reducing agents greatly improved arsenic extraction from soil samples. About 90% of the total arsenic could be extracted from all soil samples by using a combination of dithionite and EDTA. Chelating agents form strong complexation with iron, which can prevent precipitation of a new iron oxide phase and also enhance iron oxide dissolution via a non-reductive dissolution pathway.

  4. Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    B. Siddhartha Kumar

    2012-04-01

    Full Text Available Diabetes mellitus (DM and osteoporosis are the two important public health problems in India. The burden of both these conditions is expected to increase in the near future in view of changing lifestyle habits and ageing population. Indians are at risk of osteoporosis due to their low body mass index (BMI, genetic predisposition and nutritional factors. The diseases type 1 DM and type 2 DM (T2DM are associated with increased fracture risk in the disease population, in spite of difference in the bone mineral density (BMD. An increase in fracture risk is also reported among older patients with T2DM despite frequently reported normal or increased BMD. Administration of insulin stimulates osteoblast activity and bone mineral apposition rates. The impact of endogenous insulin production, insulin sensitivity, and exogenous insulin administration as an anabolic agent for bone in T2DM has not been clarified. Biguanides and sulphonylureas do not appear to have adverse effects on BMD. Preclinical evidence suggests that incretin-based drugs may be beneficial for bone, but clinical evidence to support this hypothesis is not yet available. Thiazolidinedione (TZD group of agents have been implicated in causing osteoporosis in various animal studies and some human studies available till date. The debate regarding this is issue is still ongoing. Randomized controlled studies with larger sample size preferably involving multiple centres, multiple ethnicities are required to answer these queries.

  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. Study on how nanosilver-based inorganic antibacterial agent functions on biofilm formation of Candida albicans, inside the oral cavity.

    Science.gov (United States)

    Wang, Huili; Xie, Bing

    2016-09-01

    Candida albicans is a common symbiotic fungus in the oral cavity, which can easily adhere to the surface of implanted materials. Highlighted by a broad antibacterial spectrum and potent antibacterial effects, nanosilver-based inorganic antibacterial agents (NSBIAA) are currently being hotly discussed with regard to their influences on biofilm formation of Candida albicans. This paper aims to explore the influence of NSBIAA on biofilm formation of Candida albicans. The XTT reduction method and the method of crystal violet determination were applied in measuring the influence of NSBIAA on biofilm formation of Candida albicans. In addition, biofilm morphology was determined by crystal violet staining. It was observed that with the application of liquid antibacterial agent, at a concentration of 0.62 mg/ml, the biofilm activity of Candida albicans reduced (96.1 ± 3.0) %, along with a reduction in the biomass (95.4 ± 2.7) %, and biofilm formation was not observed under an inverted microscope. NSBIAA are able to inhibit biofilm formation.

  7. Combining antihypertensive and antihyperlipidemic agents – optimizing cardiovascular risk factor management

    Directory of Open Access Journals (Sweden)

    Zamorano J

    2011-11-01

    Full Text Available José Zamorano1, Jonathan Edwards21Hospital Clinico San Carlos, Madrid, Spain; 2UBC Scientific Solutions, 5 North Street, Horsham, West Sussex, UKAbstract: Clinical guidelines now recognize the importance of a multifactorial approach to managing cardiovascular (CV risk. This idea was taken a step further with the concept of the Polypill™. There are, however, considerable patent, pharmacokinetic, pharmacodynamic, registration, and cost implications that will need to be overcome before the Polypill™ or other single-pill combinations of CV medications become widely available. However, a medication targeting blood pressure (BP and lipids provides much of the proposed benefits of the Polypill™. A single-pill combination of the antihypertensive amlodipine besylate and the lipid-lowering medication atorvastatin calcium (SPAA is currently available in many parts of the world. This review describes the rationale for this combination therapy and the clinical trials that have demonstrated that these two agents can be combined without the loss of efficacy for either agent or an increase in the incidence of adverse events. The recently completed Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial is discussed in detail. CRUCIAL was a 12-month, international, multicenter, prospective, open-label, parallel design, cluster-randomized trial, which demonstrated that a proactive intervention strategy based on SPAA in addition to usual care (UC had substantial benefits on estimated CV risk, BP, and lipids over continued UC alone. Adherence with antihypertensive and lipid-lowering therapies outside of the controlled environment of clinical trials is very low (~30%–40% at 12 months. Observational studies have demonstrated that improving adherence to lipid-lowering and antihypertensive medications may reduce CV events. One means of improving adherence is the use of single-pill combinations. Real-world observational

  8. Dose finding study of oral PSC 833 combined with weekly intravenous etoposide in children with relapsed or refractory solid tumours.

    Science.gov (United States)

    Pein, F; Pinkerton, R; Berthaud, P; Pritchard-Jones, K; Dick, G; Vassal, G

    2007-09-01

    PSC 833 is an effective MDR1 reversal agent in vitro, including studies with paediatric cancer cell lines such as neuroblastoma and rhabdomyosarcoma. This study was performed to determine the safety profile, dose limiting toxicity (DLT) and maximum tolerated dose (MTD) in children with solid tumours and to determine the influence of PSC 833 on the pharmacokinetics of co-administered etoposide. Each patient received one cycle of intravenous etoposide (100 mg/m2 daily for 3 days on three consecutive weeks) to document baseline pharmacokinetics, and subsequently the same schedule using a dose of 50 mg/m2 was given combined with PSC 833 given orally every 6h at a starting dose of 4 mg/kg. Thirty two eligible patients (23 male, median age 8.3 years) were enrolled. Neuroblastoma and rhabdomyosarcoma were the common disease types. Brain tumours were excluded. DLT was defined as any non-haematological grade 3-4 toxicity (common toxicity criteria) and using a specific toxicity scale for cerebellar toxicity. The MDT was defined as the first dose below which 2 or more patients per dose level experienced DLT. Grade 1-2 ataxia occurred in cohorts 2 and 3 (4 and 5 mg/kg, respectively). Three patients developed grade 3 neurotoxicity in the 6 mg/kg cohort and this defined the MTD. Six responses were observed (2 CR, 4 PR). Pharmacokinetic studies indicated that the clearance of etoposide was reduced by approximately 50% when combined with PSC 833. It is concluded that the toxicity profile and MDT is similar in both children and adults, as is the effect on etoposide metabolism. The study demonstrated the feasibility and safety of carrying out a paediatric phase 1 trial across European boundaries and acts as a model for future cooperative studies in rare cancers among children.

  9. Combined Oral Contraception and Obesity Are Strong Predictors of Low-Grade Inflammation in Healthy Individuals

    DEFF Research Database (Denmark)

    Sørensen, Cecilie J; Pedersen, Ole B; Petersen, Mikkel S

    2014-01-01

    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...... 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...

  10. Therapeutic value of oral supplementation with melon superoxide dismutase and wheat gliadin combination.

    Science.gov (United States)

    Romao, Susana

    2015-03-01

    Dietary antioxidant supplementation has been popular in Western countries. Various supplements have been developed in recent years, and research has been gathered from both animal and clinical research trials. In this review, the therapeutic value of oral administration of a combination of melon superoxide dismutase (SOD) and a vegetable polymer (gliadin) is evaluated. Critical examination of the effects of SOD-gliadin supplementation is carried out, with an emphasis on its impact on oxidative stress levels and on endogenous antioxidant pathways. Overall analysis of peer-reviewed published data suggests that intake of SOD-gliadin might have advantageous health effects. These conclusions are dependent on the condition or pathology under consideration. In general, the authors, who analyzed SOD-gliadin supplementation, support the use of SOD-gliadin supplementation as a complementary treatment rather than a therapeutic treatment. To further clarify the importance of dietary SOD-gliadin administration, additional large-scale clinical trials are recommended.

  11. 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.

  12. 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.

  13. 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 Panticoagulants or antiplatelet agents was documented in 16.3% and 25.1%, respectively. Overall in-hospital mortality was 23.2%. In-hospital mortality was decreased in operatively treated patients compared to conservatively treated patients (11.6% versus 24.0%; Pantiplatelet pre-treatment had a significantly higher risk of death during the hospital stay after hematoma 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.

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

    Science.gov (United States)

    Di Pierro, Francesco; Villanova, Nicola; Agostini, Federica; Marzocchi, Rebecca; Soverini, Valentina; Marchesini, Giulio

    2012-01-01

    Background 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. PMID:22924000

  15. Lipid-based cochleates: a promising formulation platform for oral and parenteral delivery of therapeutic agents.

    Science.gov (United States)

    Rao, Ravi; Squillante, Emilio; Kim, Kwon H

    2007-01-01

    Cochleates are lipid-based supramolecular assemblies that display great potential as delivery systems for systemic delivery of drugs, including peptides, proteins, vaccines, oligonucleotides, and genes. This is mainly attributed to their high stability and biocompatibility and their ability to deliver both hydrophilic and lipophilic drugs. Cochleates have a unique multilayered spiral structure, which is composed of a negatively charged phospholipid and a divalent cation, and can encapsulate diverse drug molecules of various shapes and sizes while minimizing toxicity associated with polymeric materials present in micro- and nanoparticle systems. This review describes current technological advances in the preparation methods, physicochemical characterization, and potential applications of cochleates as a drug delivery system for systemic delivery of various types of therapeutic agents.

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

    Science.gov (United States)

    Matatagui, Daniel; Fontecha, José Luis; Fernández, María Jesús; Gràcia, Isabel; Cané, Carles; Santos, José Pedro; Horrillo, María Carmen

    2014-01-01

    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. PMID:25029282

  17. 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.

  18. Love-wave sensors combined with microfluidics for fast detection of biological warfare agents.

    Science.gov (United States)

    Matatagui, Daniel; Fontecha, José Luis; Fernández, María Jesús; Gràcia, Isabel; Cané, Carles; Santos, José Pedro; Horrillo, María Carmen

    2014-07-15

    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.

  19. New oral agents for erectile dysfunction: what is changing in our practice?

    Institute of Scientific and Technical Information of China (English)

    Antonio Aversa; Andrea Fabbri

    2001-01-01

    Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and is associated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol consumption, as well as numerous age-related medical conditions, notably type-2 diabetes mellitus and cardiovascular disease. A rational step-wise approach which includes comprehensive medical and sexual history, a focused physical examination and essential laboratory tests such as fasting glucose, lipid profile and testosterone assay is to be preferred. Current diagnostic work-up does not recommend any of the specialized tests which were previously considered mandatory-i. e. penile pharmacotesting, Duplex ultrasound and nocturnal penile tumescence. Hormonal replacement therapy is appropriate only in the hypogonadal male with ED. Prior to direct intervention, the physician should consider altering modifiable risk factors or causes, although frequently insufficient to reverse ED completely. When indicated, oral therapy with new molecules (phosphodiesterase inhibitors or apomorphine) is the first-line treatment for the majority of patients because of potential benefits and lack of invasiveness.

  20. 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.

  1. FORMULATION AND EVALUATION OF ORAL CONTROLLED RELEASE DOSAGE FORM OF ANTI-HYPERTENSIVE AGENT

    Directory of Open Access Journals (Sweden)

    Lakshmi Parvathi A

    2012-12-01

    Full Text Available The aim of present investigation is preparation, characterization and evaluation of oral controlled release matrix tablets of Propranolol HCl in order to improve efficacy and to reduce the side effects. Tablets were prepared by direct compression method using different polymers like Guar gum, HPMC K4M, PVP and MCC used as the directly compressible vehicle. The granules were evaluated for pre-formulation characteristics and the tablets were subjected to post compression parameters, drug content and in-vitro dissolution release studies. In-vitro dissolution studies were carried out for 12 hrs and the results showed that among the nine formulations F8 and F9 showed good dissolution profile to control the drug release respectively. The drug release follows first order kinetics and the mechanism was found to be diffusion controlled for all the formulations (except F-9. The mechanism of drug release from F-9 was diffusion coupled with erosion. The Stability studies were carried out according to ICH guideline which indicates that the selected formulations (F8 and F9 were stable. In conclusion the results suggest that the developed matrix tablets of Propranolol HCl could perform therapeutically better than conventional dosage form, leading to improved efficacy and better patient compliance.

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

    Science.gov (United States)

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

    2017-01-01

    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. PMID:28264497

  3. 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.

  4. 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.

  5. Combination HIV prevention among MSM in South Africa: results from agent-based modeling.

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    Ron Brookmeyer

    Full Text Available HIV prevention trials have demonstrated the effectiveness of a number of behavioral and biomedical interventions. HIV prevention packages are combinations of interventions and offer potential to significantly increase the effectiveness of any single intervention. Estimates of the effectiveness of prevention packages are important for guiding the development of prevention strategies and for characterizing effect sizes before embarking on large scale trials. Unfortunately, most research to date has focused on testing single interventions rather than HIV prevention packages. Here we report the results from agent-based modeling of the effectiveness of HIV prevention packages for men who have sex with men (MSM in South Africa. We consider packages consisting of four components: antiretroviral therapy for HIV infected persons with CD4 count <350; PrEP for high risk uninfected persons; behavioral interventions to reduce rates of unprotected anal intercourse (UAI; and campaigns to increase HIV testing. We considered 163 HIV prevention packages corresponding to different intensity levels of the four components. We performed 2252 simulation runs of our agent-based model to evaluate those packages. We found that a four component package consisting of a 15% reduction in the rate of UAI, 50% PrEP coverage of high risk uninfected persons, 50% reduction in persons who never test for HIV, and 50% ART coverage over and above persons already receiving ART at baseline, could prevent 33.9% of infections over 5 years (95% confidence interval, 31.5, 36.3. The package components with the largest incremental prevention effects were UAI reduction and PrEP coverage. The impact of increased HIV testing was magnified in the presence of PrEP. We find that HIV prevention packages that include both behavioral and biomedical components can in combination prevent significant numbers of infections with levels of coverage, acceptance and adherence that are potentially achievable

  6. 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 insu

  7. Comparative evaluation of effects of combined oral anti-diabetic drugs (sulfonylurea plus pioglitazone and sulfonylurea plus metformin over lipid parameters in type 2 diabetic patients

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    Sukanta Sen

    2013-06-01

    Full Text Available Background: Type 2 diabetes is associated with significant cardiovascular morbidity and mortality. Dyslipidemia, which affects almost 50% of patients with type 2 diabetes, is a cardiovascular risk factor characterized by elevated triglyceride levels, low high-density lipoprotein (HDL cholesterol levels, and a preponderance of small, dense, low-density lipoprotein (LDL particles. In addition to their glucose-lowering properties, oral anti-diabetic agents may have effects on lipid levels, especially triglycerides (TGs, HDL-C, LDL-C and total cholesterol levels. Methods: A prospective, open-labeled, randomized, parallel-group study was carried out in sizable number of patients (n=40 of established type 2 diabetes on combined oral anti-diabetic drugs, to investigate the effects of combined oral anti-diabetic on lipid parameters who was not receiving any hypolipidemic agent in addition. Results: Statistically significant mean reduction of triglycerides (TGs of 25.1mg/dl (a 15.30% reduction from baseline value and by 13.5 mg/dl (a 8.94% reduction from baseline value in the SU (sulfonylurea plus PIO (pioglitazone and SU plus MET (metformin group respectively. Present study also shows improvement in HDL cholesterol with SU plus PIO group by 13.18% which is almost twice that observed in SU plus MET group (8.06%. Present study also shows increase in LDL cholesterol with SU plus PIO group by 2.10%, is just opposite to SU plus MET group (4.92 % decrease. With SU plus PIO group, a statistically significant mean reduction of total cholesterol (TC of 8.33mg/dl (5.14 % decrease and by 7.62 mg/dl (4.28% decrease in the SU plus MET group. Conclusions: Pioglitazone, a thiazolidinedione, has been shown to improve the lipid profile in patients with type 2 diabetes by increasing HDL-C levels and by decreasing triglyceride and total cholesterol levels in monotherapy or combination regimens with sulfonylurea. Metformin also has been shown to reduce LDL-C, TC, and TG

  8. 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

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

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

    Science.gov (United States)

    Tan, Jerry Kl; Ediriweera, Chemanthi

    2010-08-09

    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.

  11. Economic Evaluations of Thrombophilia Screening Prior to Prescribing Combined Oral Contraceptives: A Systematic and Critical Review.

    Science.gov (United States)

    Vernon, Erin; Hiedemann, Bridget; Bowie, Bonnie H

    2017-03-13

    Combined oral contraceptives (COCs) increase the risk of venous thromboembolism (VTE), particularly among women with inherited clotting disorders. The World Health Organization classifies combined hormonal contraception as an "unacceptable health risk" for women with thrombogenic mutations but advises against universal thrombophilia screening before prescribing COCs given the low prevalence of thrombophilia and high screening costs. Through the lens of lifetime costs and benefits, this paper systematically and critically reviews all published economic evaluations of thrombophilia screening prior to prescribing COCs. We searched relevant databases for economic evaluations of thrombophilia screening before prescribing COCs. After extracting the key study characteristics and economic variables, we evaluated each article using the Quality of Health Economic Studies (QHES) and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) instruments. Seven economic evaluations of thrombophilia screening before prescribing COCs met our inclusion criteria. Only the two economic evaluations focusing exclusively on selective screening exceeded the 75-point threshold for high-quality economic studies based on the QHES instrument, whereas only one of these exceeded the 85% CHEERS threshold. Only three of the seven economic evaluations performed sensitivity analysis on key parameters. Most studies underestimated the benefits of thrombophilia screening by comparing one-time costs of genetic screening against benefits per person-year, thus implicitly assuming a 1-year duration of COC use, neglecting the long-term implications of VTE and/or neglecting the lifetime benefits of awareness of inherited thrombophilia. Our review highlights the lack of methodologically rigorous economic evaluations of universal thrombophilia screening before prescribing COCs.

  12. Oral heparin: status review

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    Gomez-Orellana Isabel

    2006-05-01

    Full Text Available Abstract Unfractionated heparin and low molecular weight heparin are the most commonly used antithrombotic and thromboprophylactic agents in hospital practice. Extended out-of-hospital treatment is inconvenient in that these agents must be administered parenterally. Current research is directed at development of a safe and effective oral antithrombotic agent as an alternative for the effective, yet difficult to use vitamin K antagonists. A novel drug delivery technology that facilitates transport of drugs across the gastrointestinal epithelium has been harnessed to develop an oral dosage form of unfractionated heparin. Combining unfractionated heparin with the carrier molecule, sodium N-(8 [2-hydroxybenzoyl]amino caprylate, or SNAC has markedly increased the gastrointestinal absorption of this drug. Preclinical and clinical studies to-date suggests that oral heparin-SNAC can confer a clinical efficacious effect; further confirmation is sought in planned clinical trials.

  13. Acute oral toxicity study of ethanol extract of Ceiba pentandra leaves as a glucose lowering agent in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Hadiza Lami Muhammad; Adamu Yusuf Kabiru; Musa Bola Busari; Abdullah Mann; Abubakar Siddique Abdullah; Abdulrazaq Taye Usman; Usman Adamu

    2016-01-01

    Objective: To evaluate the use of Ceiba pentandra (C. pentandra) as a glucose lowering agent and the attendant physiological changes in albino rats. Methods: Acute oral toxicity study of the extract was carried out by the administration of 10, 100, 1 000, 1 600, 2 900, and 5 000 mg/kg body weight of C. pentandra to rats in their respective groups. Twenty healthy albino rats weighing between 140 and 150 g were randomly allotted to five groups of four rats each. 100 mg/kg body weight of alloxan monohydrate was i.p. administered to rats and rats with blood glucose ? 200 mg/dL were considered diabetic. 5 mg/kg body weight of standard drug, 200 and 400 mg/kg body weight of ethanol extract of C. pentandra were orally administered to diabetic rats in their respective groups once daily for 12 days while the control groups received 0.1 mL of normal saline for the same period. The blood glucose was checked after every 4 days and the experiment was terminated on the 17th day. Results: The safe dose (LD50) of the extract was greater than 5 000 mg/kg body weight. The extract treated groups exhibited a remarkable reduction in blood glucose [(87.72 ± 7.67) mg/dL for 200 mg/kg body weight dose and (86.33 ± 4.54) mg/dL for 400 mg/kg body weight dose] competitively with the normoglycemic group [(88.71 ± 4.56) mg/dL]. The body weight of the extract and standard drug treated groups appreciated significantly (P Conclusions: Ethanol extract of C. pentandra has glucose lowering effect and can ameliorate the biochemical abnormalities associated with diabetes mellitus.

  14. Dose finding in a low-dose 21-day combined oral contraceptive containing gestodene.

    Science.gov (United States)

    Lüdicke, F; Sullivan, H; Spona, J; Elstein, M

    2001-10-01

    An open label, non-comparative study was carried out in 22 women over a total of five cycles. After an untreated cycle, oral administration of 20 microg ethinyl estradiol (EE) with 50 microg gestodene (GST) (tablets taken daily for 21 days with a break of 7 days) was commenced, and three treatment cycles were followed by an untreated follow-up control cycle. The ability of this formulation to inhibit ovulation and suppress ovarian activity was assessed by using hormonal parameters and ultrasound. One ovulation occurred during treatment. Luteinized unruptured follicles were observed in three cases in the second treatment cycle and in one case during the third treatment cycle. Follicle-like structures larger than 13 mm associated with a serum estradiol level of more than 30 pg/mL were noted in 19% of the women in the first treatment cycle. The rate of active follicle-like structures was 43% in the second treatment cycle and 28% in the third treatment cycle. The results were compared with previously reported findings of a preparation containing 20 microg EE and 75 microg GST. With regard to ovarian grading and endogenous hormone secretion, considerably more residual ovarian activity, with all parameters examined, was found in the 20 microg EE and 50 microg GST preparation compared to the 20 microg EE and 75 microg GST preparation. It was concluded that the 20 microg EE and 50 microg GST preparation administered for 21 days does not meet the requirements of a combined oral contraceptive with respect to ovulation inhibition.

  15. Scrapie Agent (Strain 263K can transmit disease via the oral route after persistence in soil over years.

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    Bjoern Seidel

    Full Text Available The persistence of infectious biomolecules in soil constitutes a substantial challenge. This holds particularly true with respect to prions, the causative agents of transmissible spongiform encephalopathies (TSEs such as scrapie, bovine spongiform encephalopathy (BSE, or chronic wasting disease (CWD. Various studies have indicated that prions are able to persist in soil for years without losing their pathogenic activity. Dissemination of prions into the environment can occur from several sources, e.g., infectious placenta or amniotic fluid of sheep. Furthermore, environmental contamination by saliva, excrements or non-sterilized agricultural organic fertilizer is conceivable. Natural transmission of scrapie in the field seems to occur via the alimentary tract in the majority of cases, and scrapie-free sheep flocks can become infected on pastures where outbreaks of scrapie had been observed before. These findings point to a sustained contagion in the environment, and notably the soil. By using outdoor lysimeters, we simulated a contamination of standard soil with hamster-adapted 263K scrapie prions, and analyzed the presence and biological activity of the soil-associated PrP(Sc and infectivity by Western blotting and hamster bioassay, respectively. Our results showed that 263K scrapie agent can persist in soil at least over 29 months. Strikingly, not only the contaminated soil itself retained high levels of infectivity, as evidenced by oral administration to Syrian hamsters, but also feeding of aqueous soil extracts was able to induce disease in the reporter animals. We could also demonstrate that PrP(Sc in soil, extracted after 21 months, provides a catalytically active seed in the protein misfolding cyclic amplification (PMCA reaction. PMCA opens therefore a perspective for considerably improving the detectability of prions in soil samples from the field.

  16. Uso do contraste oral negativo em exames de colangiografia por ressonância magnética Use of oral negative contrast agent in magnetic resonance cholangiopancreatography examinations

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    Mário de Melo Galvão Filho

    2002-10-01

    Full Text Available OBJETIVO: Realizamos estudo prospectivo das vias biliares e pancreáticas através de colangiografia por ressonância magnética, com a utilização de meio de contraste oral negativo. Os nossos objetivos foram verificar se este novo meio de contraste melhora a visualização das vias biliar e pancreática, além de identificar a freqüência de efeitos colaterais ao contraste e sua aceitação pelo paciente. MATERIAL E MÉTODO: Quinze voluntários (oito homens e sete mulheres com idades variando entre 18 e 54 anos (média de 29 anos, sem queixas ou cirurgias abdominais, foram submetidos a colangiografia por ressonância magnética. Foram realizadas duas seqüências colangiográficas em apnéia, antes e cinco minutos após a ingestão de 300 ml de contraste oral negativo. Os exames foram realizados em equipamento operando a 1,0 T. RESULTADOS: Setenta e três por cento dos voluntários consideraram o gosto ruim ou muito ruim, sugerindo uma aceitação discutível; 27% dos voluntários apresentaram náuseas; 20%, cólicas; 14%, azia ou parestesia labial; e 7%, diarréia. A visualização da via biliar extra-hepática foi considerada melhor após o contraste oral negativo em 9/15 voluntários (60% e do ducto pancreático principal em todos os cinco em que havia interposição de alças. CONCLUSÃO: O contraste oral negativo melhora a visualização dos ductos hepatocolédoco e pancreático principal em exames de colangiografia por ressonância magnética, apesar da baixa aceitação e dos seus efeitos colaterais.OBJECTIVE: The aim of this prospective study was to investigate the feasibility of using a negative oral contrast agent to null the bowel signal during magnetic resonance cholangiopancreatography. MATERIAL AND METHOD: Fifteen healthy volunteers with no previous history of pancreaticobiliary disease or surgery were imaged with a single-shot fast spin-echo pulse sequence, using a magnetic resonance imaging system operating at 1.0 T. Data

  17. Preclinical changes in weight of scrapie-infected mice as a function of scrapie agent-mouse strain combination.

    Science.gov (United States)

    Carp, R I; Callahan, S M; Sersen, E A; Moretz, R C

    1984-01-01

    Several inbred strains of mice were injected with different scrapie agents and their total body weight was monitored throughout the incubation period. As a control, mice were injected with normal mouse brain homogenate. For most combinations of scrapie agent and mouse strain, weights during the preclinical phase were similar to or lower than the average weight of controls. For some combinations there was a significant increase in weight (compared to controls) during the latter part of the preclinical phase of disease. The effect was dependent on both agent and mouse strain, i.e., in some cases a mouse strain showed the increase with one scrapie agent but not another and some scrapie agents caused the increase in one inbred strain of mouse but not in another strain. The increase in weight was due to accumulations of fat rather than a generalized increase in weight of various organs. With one mouse strain (SJL), there was increased vacuolation seen in the hypothalamus of mice injected with scrapie agents that showed the increase in weight compared to the lesion intensity with an agent which did not cause the weight increase.

  18. A COMPARATIVE EVALUATION OF A COMBINATION OF MIDAZOLAM AND KETAMINE VERSUS MIDAZOLAM OR KETAMINE ALONE AS ORAL PREMEDICATION FOR CHILDREN

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    Anjali P.

    2015-09-01

    Full Text Available This prospective double blind randomized study was conducted to compare the efficacy of combination of oral ketamine and midazolam with oral midazolam or ketamine alone in terms of acceptability, anxiolysis, sedation and side effects. AIMS AND OBJECTIVE: Compare the efficacy of oral midazolam, oral ketamine and combination of these two drugs, as pre medication in terms of acceptability, sedation, anxiolysis and side effects in paediatric children and t o evaluate whether the addition of oral midazolam to oral ketamine reduces the side effects of oral Ketamine. METHODS: In this randomized prospective study, 90 children of (age 1 - 8 years either sex, ASA grade I and II were randomly allocated to three groups of thirty each. Group M received midazolam 0.75mg/kg, Group K received ketamine 6 mg/kg and Group M+K received midazolam 0.5 mg/kg and ketamine 3 mg/kg via oral route. Formulations of the drugs were given to the children to swallow after mixing with apple juice. The children were separated from their parents 45 minutes after administration of the drug and were taken inside the operation theatre. Acceptability of the drug, time of onset of sedation, level of sedation and anxiolysis at the time of separation from parents and sedation at the time of induction of anaesthesia was noted. Any side effect after administration of the drug and in post - operative period was looked for. RESULTS: The Group K had better acceptance as compared to Group M and Group M+K . The onset of sedation was faster in Group M+K as compared to Group K and Group M, but not statistically significant . The sedation as well as anxiolysis in all the three groups was found to be acceptable at the time of separation; however it was not found to be satisfactory at the time of induction. Incidence of side effects was more in Group K as compared to the other two groups. CONCLUSION: The combination of oral midazolam and oral ketamine in low dose is better premedication than the

  19. Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer.

    Science.gov (United States)

    Nagaprashantha, Lokesh Dalasanur; Vatsyayan, Rit; Singhal, Jyotsana; Fast, Spence; Roby, Rhonda; Awasthi, Sanjay; Singhal, Sharad S

    2011-11-01

    The present study was conducted to determine the efficacy of novel flavonoid vicenin-2 (VCN-2), an active constituent of the medicinal herb Ocimum Sanctum Linn or Tulsi, as a single agent and in combination with docetaxel (DTL) in carcinoma of prostate (CaP). VCN-2 effectively induced anti-proliferative, anti-angiogenic and pro-apoptotic effect in CaP cells (PC-3, DU-145 and LNCaP) irrespective of their androgen responsiveness or p53 status. VCN-2 inhibited EGFR/Akt/mTOR/p70S6K pathway along with decreasing c-Myc, cyclin D1, cyclin B1, CDK4, PCNA and hTERT in vitro. VCN-2 reached a level of 2.6±0.3μmol/l in serum after oral administration in mice which reflected that VCN-2 is orally absorbed. The i.v. administration of docetaxel (DTL), current drug of choice in androgen-independent CaP, is associated with dose-limiting toxicities like febrile neutropenia which has lead to characterization of alternate routes of administration and potential combinatorial regimens. In this regard, VCN-2 in combination with DTL synergistically inhibited the growth of prostate tumors in vivo with a greater decrease in the levels of AR, pIGF1R, pAkt, PCNA, cyclin D1, Ki67, CD31, and increase in E-cadherin. VCN-2 has been investigated for radioprotection and anti-inflammatory properties. This is the first study on the anti-cancer effects of VCN-2. In conclusion, our investigations collectively provide strong evidence that VCN-2 is effective against CaP progression along with indicating that VCN-2 and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer.

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

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    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

  1. Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use

    NARCIS (Netherlands)

    Rad, M.; Kluft, C.; Kam, M.L. de; Meijer, P.; Cohen, A.F.; Grubb, G.S.; Constantine, G.D.; Burggraaf, J.

    2011-01-01

    Objectives?To compare the effects of a combined oral contraceptive (COC) taken continuously with those of one of similar composition taken cyclically on 30 variables related to haemostasis, lipids, carbohydrates, bone metabolism, and sex hormone-binding globulin (SHBG). Methods?Randomised,

  2. Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use

    NARCIS (Netherlands)

    Rad, M.; Kluft, C.; Kam, M.L. de; Meijer, P.; Cohen, A.F.; Grubb, G.S.; Constantine, G.D.; Burggraaf, J.

    2011-01-01

    Objectives?To compare the effects of a combined oral contraceptive (COC) taken continuously with those of one of similar composition taken cyclically on 30 variables related to haemostasis, lipids, carbohydrates, bone metabolism, and sex hormone-binding globulin (SHBG). Methods?Randomised, open-labe

  3. Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use

    NARCIS (Netherlands)

    Rad, M.; Kluft, C.; Kam, M.L. de; Meijer, P.; Cohen, A.F.; Grubb, G.S.; Constantine, G.D.; Burggraaf, J.

    2011-01-01

    Objectives?To compare the effects of a combined oral contraceptive (COC) taken continuously with those of one of similar composition taken cyclically on 30 variables related to haemostasis, lipids, carbohydrates, bone metabolism, and sex hormone-binding globulin (SHBG). Methods?Randomised, open-labe

  4. Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes.

    Science.gov (United States)

    Hu, Changyun; Ding, Heyuan; Zhang, Xiaojun; Wong, F Susan; Wen, Li

    2013-08-01

    Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease, although B cells also play an important role in T1D development. Both T cell- and B cell-directed immunotherapies have shown efficacy in the prevention and reversal of T1D. However, whether the combined strategy of targeting both T and B cells could further improve therapeutic efficacy remains to be explored. We show that combined treatment with intravenous antihuman CD20 (hCD20) and oral anti-CD3 significantly delays diabetes development in prediabetic hCD20 transgenic NOD mice. More importantly, the combined treatment reverses diabetes in >60% of mice newly diagnosed with diabetes. Further mechanistic studies demonstrated that the addition of oral anti-CD3 to the B-cell depletion therapy synergistically enhances the suppressive function of regulatory T cells. Of note, the oral anti-CD3 treatment induced a fraction of interleukin (IL)-10-producing CD4 T cells in the small intestine through IL-10- and IL-27-producing dendritic cells. Thus, the findings demonstrate that combining anti-CD20 and oral anti-CD3 is superior to anti-CD20 monotherapy for restoring normoglycemia in diabetic NOD mice, providing important preclinical evidence for the optimization of B cell-directed therapy for T1D.

  5. Phase i and pharmacological study of pazopanib in combination with oral topotecan in patients with advanced solid tumours

    NARCIS (Netherlands)

    Kerklaan, B. Milojkovic; Lolkema, M. P J; Devriese, L. A.; Voest, E. E.; Nol-Boekel, A.; Mergui-Roelvink, M.; Langenberg, M.; Mykulowycz, K.; Stoebenau, J.; Lane, S.; Legenne, P.; Wissel, P.; Smith, D. A.; Giantonio, B. J.; Schellens, J. H M; Witteveen, P. O.

    2015-01-01

    Background: This phase I study evaluated the safety, tolerability, maximum tolerated dose (MTD) and pharmacokinetics of two dosing schedules of oral topotecan in combination with pazopanib in patients with advanced solid tumours. Methods: Stage I of this study was to determine whether there was an i

  6. ROSIN MICROSPHERES AS TASTE MASKING AGENT IN ORAL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Shery Jacob

    2012-09-01

    Full Text Available Natural resources in general and plant materials in particular are receiving more attention due to their safety as pharmaceutical excipients. Present work assessed the combination potential of natural hydrophobic resin, rosin, and synthetic polymer ethyl cellulose to mask the abhorrent inherent taste of ambroxol hydrochloride, by microencapsulation technique, and its possibility to formulate as a fast dissolving dosage form. Being of natural origin, rosin and its derivatives are biodegradable and biocompatible. Although It has excellent film forming property the native rosin films are brittle and break easily upon handling. The film forming properties of rosin was modified by substituting a part with ethyl cellulose.The prepared rosin-ethyl cellulose composite microspheres by emulsion solvent evaporation technique possessed good sphericity, smooth surface morphology, uniform and narrow size distribution (1090 µm, when analyzed by scanning electron microscopy. PEG 400 was used as plasticizer because of its hydrophilicity, biocompatibility and their excellent plasticizing activity. Method of preparation has influenced the particle size and drug loading efficiency. Drug-polymer compatibility was confirmed by Fourier transform infrared spectroscopy and thin layer chromatography. DSC studies revealed that the drug was molecularly dispersed inside the microspheres in the form of solid solution. Sensory studies in healthy human volunteers indicated that the taste and palatability were significantly improved by microencapsulation. This study demonstrated that rosin could be a right choice in developing patient favored formulations for bitter drugs and can be utilized in fast disintegrating dosage forms as well.

  7. Oral tranexamic acid with fluocinolone-based triple combination cream versus fluocinolone-based triple combination cream alone in melasma: An open labeled randomized comparative trial

    Directory of Open Access Journals (Sweden)

    Tanmay Padhi

    2015-01-01

    Full Text Available Background : Melasma is a common acquired cause of facial hyperpigmentation with no definitive therapy. Tranexamic acid, a plasmin inhibitor, has demonstrated depigmenting properties and combining this oral drug with other modalities of treatment has shown promising results. Objectives : To compare the efficacy of a combination of oral tranexamic acid and fluocinolone-based triple combination cream with that of fluocinolone-based triple combination cream alone in melasma among Indian patients. Materials and Methods : 40 patients of melasma of either sex attending to dermatology OPD were enrolled in this study. Participants were randomly divided into two groups with 20 patients in each group. Group A patients were asked to apply the cream only and Group B patients received oral tranexamic acid 250 mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01%, tretinoin 0.05%, and hydroquinone 2% once daily for 8 weeks. Response was evaluated using melasma area severity index (MASI at baseline, 4 weeks, and 8 weeks. Results : 40 patients completed the study. The MASI scores at baseline, 4 weeks and 8 weeks in group A were 15.425 + 1.09, 11.075 + 9.167 and 6.995 + 6.056 respectively and in group B 18.243 + 1.05, 6.135 + 4.94 and 2.19 + 3.38. Intergroup comparison showed a faster reduction in pigmentation in Group B as compared to Group A and the results were statistically significant at 4 weeks (P value 0.014 and 8 weeks (P value 0.000. The efficacy was maintained throughout the 6-month follow-up period. Conclusion: Addition of oral tranexamic acid to fluocinolone-based triple combination cream results in a faster and sustained improvement in the treatment of melasma.

  8. Gold nanoparticles combined with highly expressed amber suppressor tRNA: a future antibacterial agent

    Directory of Open Access Journals (Sweden)

    Xiaoda Song

    2010-10-01

    Full Text Available "nAmber suppressor tRNA is a mutant allele coding for a tRNA, whose anticodon is altered in such a way that the suppressor tRNA inserts an amino acid at an amber codon in translation which leads to suppressing (preventing termination. And some Amber suppressor tRNA strains were found. We propose that gold nanoparticles combined with highly expressed amber suppressor tRNA which can be uptake by cells and recognized by AARS (aminoacyl tRNA synthetase will lead to the formation of C-terminally extended proteins. These proteins probably will not work properly, leading bacteria's death. Because of the difference of tRNA between prokaryotic and eukaryotic cells, even between different bacteria species, this amber suppressor tRNA is orthogonal for other species and cannot be recognized by AARS, therefore has no toxicity to other species. May it be an excellent antibacterial agent in the future? In this article we provide a screening method for the highly expressed amber suppressor tRNA using randomly bases mutation, radioactive selection, activity test in vivo, and finally linkage of the amber suppressor tRNA to gold nanoparticles.

  9. [Gynecological use of a phlebokinetic drug with special reference to its combination with oral contraceptives].

    Science.gov (United States)

    Cazzola, D

    1975-09-30

    Controlled experiments confirmed the therapeutic usefulness in gynecology of a phlebokinetic drug, in which EPL (polyunsaturated phosphatidylcholine) was combined with escine and rutine. The drug is particularly recommended for the prophylaxis and treatment of vein disorders caused by oral contraceptives. A total of 75 patients were treated with the drug (Essaven), in addition to the usual treatment (such as anticoagulants), while 75 controls received the usual treatment only. Results were excellent in cases of varicose veins, where the symptoms were eliminated in almost all cases. In cases of phlebitis and thrombophlebitis, the response was less univocal, but a definite improvement was evident in a good number of cases treated with Essaven; the drug also favored the return to normal conditions after thrombophlebitis attacks, reducing the duration of their painful aftereffects. The drug can be used daily for very long periods without side effects. It can also be used safely during pregnancy, without adverse effects on the fetus and on delivery. It is regarded as ideal to avoid the side effects of contraceptives on the venous system.

  10. SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION OF MESALAMINE AND PREDNISOLONE IN COMBINED ORAL DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Dr. Sanjay Jain et al

    2012-10-01

    Full Text Available The objective of this study was to develop simple, precise, accurate, reproducible and economical vireodt's method for simultaneous estimation of mesalamine (MSM and prednisolone (PRD in combined oral dosage form. The method involved measurement of absorbance at two wavelengths, 332nm and 246nm, λmax of MSM and PRD, respectively in phosphate buffer (pH 7.4 with dimethyl formamide (DMF as cosolvent. The linearity was obtained in the concentration range of 5-50 µg/ml and 2-20 µg/ml for MSM and PRD, respectively. The average percent recovery of MSM and PRD was found to be 99.19+0.78% and 99.71+0.82%, respectively. The accuracy and precision were determined and recovery studies confirmed the accuracy of the developed method that was carried out following the International Conference on Harmonization (ICH guidelines. The recovery study was carried out by standard addition method. The proposed method was found to be rapid, specific, precise, accurate, and reproducible and can be successfully applied for the routine analysis of MSM and PRD in pharmaceutical dosage form.

  11. Cardiovascular disease and combined oral contraceptives: reviewing the evidence and balancing the risks.

    Science.gov (United States)

    Farley, T M; Meirik, O; Collins, J

    1999-01-01

    Cardiovascular risks have been a concern since combined oral contraceptives (OCs) were first introduced. In the past four years new, mostly reassuring information on the safety of modern, low oestrogen dose OCs has become available. However, in 1995 the new information showed higher venous thromboembolism (VTE) risk for OCs containing desogestrel and gestodene compared with levonorgestrel- or norethindrone-containing OCs. The controversial responses by national authorities, their scientific and public health merits were hotly debated and many considered the differences in risk small and resulted from bias and/or confounding. We discuss these arguments and conclude they lack empirical support or cannot account for the 2-fold increased risk. The risk of ischaemic stroke and myocardial infarction (MI) associated with low oestrogen dose OCs are very small in women without cardiovascular risk factors, while increased risk of haemorrhagic stroke is confined to women >35 years of age. Applying the most recent risks to models of OC-attributable events and deaths, OC-attributable mortality in women mortality (about 90 per million women of reproductive age annually in the UK) such risks appear small. Over the age of 35 years, OC-attributable mortality is a more important concern, particularly among smokers. In the absence of any appreciable OC-attributable mortality in young healthy women, the additional VTE risk for third compared with second generation OCs should be considered when women choose which OC to use.

  12. Post-marketing Surveillance for Combined Oral Contraceptive Containing Desogestrel (Marvelon?) in Chinese Rural Areas

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To assess the side effects and the continuation rate of combined oral contraceptive (COC) containing desogestrel (Marvelon ) during 12 months. Methods This was a post-marketing surveillance study on Marvelon COC among 870 healthy rural women in 5 different counties of Jiangsu Province during 12 months. Results About 24.02% of the women who used Marvelon COC experienced side effects during 12 months. Gastrointestinal disorder, bleeding/spotting and chloasma were ranked the first three in the side effects. The rate of side effects of Marvelon COC users during the first 3 months in southern area of Jiangsu was significantly higher than that of users in northern area of Jiangsu. Most of the users did not experience obvious weight changes i.e., loss or increase in weight of more than 5 kg during 12 months. Blood pressure and biochemical indicators of almost 99% among users were within the normal range. The gross cumulative continuation rate for 12 months was 83.14%; the most common medical reason for discontinuation was gastrointestinal disorder. There was an increased risk of discontinuation use among women with lower educational level.Conclusion Marvelon COC brought fewer side effects and was well accepted when applied in Chinese rural women.

  13. Combined Oral and Intravenous Immunization Stimulates Strong IgA Responses in Both Systemic and Mucosal Compartments.

    Science.gov (United States)

    Yang, Zhe; Zhao, Qing; Gao, Yun-An; Zhang, Wei

    2016-01-01

    To investigate the influence of immunization routes onIgG, IgA and IgM production in systemic and mucosal compartments, we immunized mice with keyhole limpet hemocyanin (KLH) via oral, intranasal (i.n.) or subcutaneous (s.c.) routes alone or combined with the intravenous (i.v.) route. We found that administering antigen intravenously could affect antibody production and formation of antibody secreting cells (ASCs) depending on the immunization route previously used. Combined oral/i.v. immunization but not s.c./i.v. immunization caused a great increase of IgA ASCs in the spleen and enhanced IgA production in the small intestine and serum. Combined i.n./i.v. immunization could also increase IgA ASCs in the spleen and enhance IgA production in serum but had no effect on IgA production in the small intestine. Oral/i.v. immunization caused increase of IgG ASCs in both the spleen and bone marrow. In comparison, combined i.n./i.v. and s.c./i.v. immunization could increase IgG ASCs in the spleen but not in bone marrow. Intravenous administration of KLH in mice that had been immunized via oral, i.n. or s.c. routes caused some increase of IgM ASCs in the spleen but not in bone marrow. In conclusion, combined oral and i.v. administration of an antigen can induce fast and strong immune responses, especially for IgA, in both systemic and mucosal compartments.

  14. A comparison of the sedative effect of oral versus nasal midazolam combined with nitrous oxide in uncooperative children.

    Science.gov (United States)

    Musani, I E; Chandan, N V

    2015-10-01

    To compare a combination of oral midazolam (0.2 mg/kg body weight) and nitrous oxide-oxygen sedation with a combination of intranasal midazolam (0.1 mg/kg body weight) and nitrous oxide-oxygen sedation for effectiveness, patient acceptability and safety profile in controlling the behaviour of uncooperative children. Thirty children, 4-10 years of age, referred for dental treatment were included in the study with a crossover design. Each patient was sedated with a combination of either oral midazolam and nitrous oxide-oxygen sedation or intranasal midazolam and nitrous oxide-oxygen sedation at subsequent dental treatment visits. During the treatment procedure, the study recorded scales for drug acceptability, onset of sedation, acceptance of nasal mask, sedation, behavioural, safety, overall behaviour and alertness. The grade of acceptability of midazolam in both groups was consistently good. There was a significant difference (p midazolam. The mean time of onset for oral midazolam was 20.1 (17-25) min and for intranasal midazolam 12.1 (8-18) min. The efficacy profile of the present study included: acceptance of nasal mask, sedation score, crying levels, motor movements and overall behaviour scores. The results did not show any statistically significant differences. All the parameters were highly satisfactory. The difference in alertness was statistically significant (p value midazolam. The intranasal route of midazolam administration has a quick onset of action and a quick recovery of the patient from sedation as compared to the oral route of midazolam administration. Midazolam administered through the intranasal route is as effective as the oral route at a lower dosage. Therefore, it is an effective alternative to oral route for a paediatric dental situation.

  15. 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

  16. Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab

    Science.gov (United States)

    2015-08-03

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  17. Application of Oral Lactulose in Combination With Polyethylene Glycol Electrolyte Powder for Colonoscopy Bowel Preparation in Patients With Constipation.

    Science.gov (United States)

    Lu, Juan; Cao, Qin; Wang, Xiaochun; Pu, Jianbin; Peng, Xuelian

    2016-01-01

    The aim of the study was to investigate the efficacy of combined application of lactulose oral solution and polyethylene glycol electrolyte powder compared with conventional method in preparing for colonoscopy bowel cleanliness in patients with constipation. Ninety patients, who had constipation and needed to have colonoscopy, were divided into study group and control group with 45 cases in each group, respectively. One day before the colonoscopy, patients in the experimental group were given lactulose oral solution and polyethylene glycol electrolyte powder, whereas the patients in the control group were given oral polyethylene glycol electrolyte powder only. The following parameters were then obtained: time of the first defecation (duration of the time from taking the drugs to the first bowel movement), defecation frequency, completion of bowel cleaning (duration from the first bowel movement to the stool becoming clear), and adverse reaction. Cleansing effect in the study group bowel preparation was significantly better than that in the control group (P 0.05). Combined application of lactulose oral solution and polyethylene glycol electrolyte powder is superior to the conventional method of polyethylene glycol electrolyte powder alone for colonoscopy bowel preparation in patients with constipation. Therefore, combined clinical application of the 2 compounds is strongly recommended for colonoscopy bowel preparation in patients with constipation.

  18. 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

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Altinok, Magda Lambaa; Mumm, Hanne

    2014-01-01

    inclusion. OCP and M+OCP were superior to M regarding reduction in free T levels. Conclusions: M treatment alone or in combination with OCP was associated with weight loss and improved body composition compared with OCP, whereas free T levels decreased during M+OCP or OCP. Combined treatment with M......Context: Central obesity in polycystic ovary syndrome (PCOS) is associated with increased inflammatory markers and increased risk for type 2 diabetes. Objective: The objective of the study was to evaluate whether treatment with metformin (M) or M combined with oral contraceptive pills (OCPs...... (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. Main Outcome Measures: Changes in weight at 6 and 12...

  19. Optimization of dose and technique for magnetic resonance studies with an oral contrast agent; Ottimizzazione della dose e della tecnica di esame nell'utilizzazione di un mezzo di contrasto orale nella risonanza magnetica

    Energy Technology Data Exchange (ETDEWEB)

    Broglia, L.; Tortora, A.; Maccioni, F.; Arpesani, R.; Marcelli, G.; Ascarelli, A.; Rossi, P. [Rome Policlinico Umberto I, Rome (Italy). Ist. di radiologia

    1999-05-01

    The aim of the study was to optimize the dose, scan delay and sequences for use in magnetic resonance (MR) studies with an oral contrast agent (FerriSeltz, Bracco Spa, Milan, Italy) to obtain positive or negative contrast enhancement in the bowel lumen. Ferric ammonium citrate, being positive or negative contrast agent according to its dilution, permits to tailor the dose to optimize bowel lumen opacification. [Italian] Obiettivo del lavoro e' stato di ottimizzare la dose, il ritardo dell'esecuzione dell'esame e le sequenze da selezionare utilizzando un mezzo di contrasto in risonanza magnetica con somministrazione orale (FerriSeltz, Bracco SpA) per ottenere l'opacizzazione positiva o negativa dell'intestino. Il FerriSeltz si comporta come un mdc positivo o negativo sulla base della sua diluizione e pertanto consente di adattare la dose per ottenere il tipo di opacizzazione adeguata alla malattia da esaminare.

  20. 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.

  1. 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)

    G R 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.

  2. 吉非罗齐对临床几种常用口服降糖药的作用%Effects of Gemfibrozil on several commonly used oral hypoglycemic agents

    Institute of Scientific and Technical Information of China (English)

    淡海丽; 易飞

    2011-01-01

    Drug interactions, particularly the studies of interaction between pharmacokinetics become a hot spot in recent years.Gemfibrozil is a lipid-lowering drugs commonly used in clinical, and there are many opportunities hyperlipidemia be in diabetes clinical situation, so whether there are interactions between gemfibrozil and oral agents should also be the concern of clinicians.We review the effect of Gemfibrozil to the pharmacokinetics and pharmacodynamics of several commonly used oral hypoglycemic drug, and to analyze its mechanism.Gemfibrozil inhibited CYP2C and significant effect the pharmacokinetics and pharmacodynamics of oral hypoglycemic drug, so monitoring the blood glucose concentrations in time or adjust the dosage of oral hypoglycemic agents when they are combined in clinical is necessary.%药物相互作用,尤其是药代学的相互作用的研究近年来成为热点.吉非罗齐是一个临床常用的降脂药物,而在临床高脂血症合并糖尿病情况较多,所以吉非罗齐与口服降糖药合用后是否有相互作用也应该是临床医生的关注点.本文综述吉非罗齐对临床几种常用口服降糖药的药代学和药效学的影响,及从其机制上予以分析.吉非罗齐通过对CYP2C的抑制作用而明显影响口服降糖药的药代学及药效学,所以在临床上合用时需及时监测血糖的浓度或调整口服降糖药的用量.

  3. Microleakage of Class II Combined Amalgam-Composite Restorations Using Different Composites and Bonding Agents

    Directory of Open Access Journals (Sweden)

    F. Sharafeddin

    2008-09-01

    Full Text Available Objective: The purpose of the present study was to assess the microleakage of composite restorations with and without a cervical amalgam base and to compare the results of dif-ferent composites and bonding agents.Materials and Methods: One hundred and twenty mesio-occlusal (MO and disto-occlusal (DO Class II cavities were prepared on sixty extracted permanent premolar teeth. The teeth were randomly divided into four groups of 30 and restored as follows:In group A, the mesio-occlusal cavity (MO, Scotchbond multi purpose plus + Z250 and in the disto-occlusal (DO cavity, Prompt-L-Pop + Z250 were applied. As for group B, in the MO and DO cavities, Clearfil SE Bond + Clearfil APX, and varnish + amalgam (In box + Clearfil SE Bond + Clearfil APX were used respectivelywhile in group C; the teeth were restored with amalgam and varnish mesio-occlusally and with amalgam only disto-occlusally. As for group D, varnish + amalgam (in box + Scotchbond multi purpose plus + Z250 were applied mesio-occlusally and Varnish + Amalgam (in box + Prompt–L–Pop + Z250 disto-occlusally.Marginal leakage was assessed by the degree of dye penetration into various sections of the restored teeth. Chi-square and Fisher's exact tests were used for data analysis.Results: Microleakage in gingival margin was more than that in occlusal margin (P<0.05 and microleakage of combined amalgam-composite restorations was significantly lower than that of conventional composite and amalgam restorations.Conclusion: Marginal microleakage decreased by using amalgam at the base of the box in Class II composite restorations.

  4. In vitro and in vivo clinical pharmacology of dimethyl benzoylphenylurea, a novel oral tubulin-interactive agent.

    Science.gov (United States)

    Rudek, Michelle A; Zhao, Ming; Smith, Nicola F; Robey, Robert W; He, Ping; Hallur, Gurulingappa; Khan, Saeed; Hidalgo, Manuel; Jimeno, Antonio; Colevas, A Dimitrios; Messersmith, Wells A; Wolff, Antonio C; Baker, Sharyn D

    2005-12-01

    Dimethyl benzoylphenylurea (BPU) is a novel tubulin-interactive agent with poor and highly variable oral bioavailability. In a phase I clinical trial of BPU, higher plasma exposure to BPU and metabolites was observed in patients who experienced dose-limiting toxicity. The elucidation of the clinical pharmacology of BPU was sought. BPU, monomethylBPU, and aminoBPU were metabolized by human liver microsomes. Studies with cDNA-expressed human cytochrome P450 enzymes revealed that BPU was metabolized predominantly by CYP3A4 and CYP1A1 but was also a substrate for CYP2C8, CYP2D6, CYP3A5, and CYP3A7. BPU was not a substrate for the efflux transporter ABCG2. Using simultaneous high-performance liquid chromatography/diode array and tandem mass spectrometry detection, we identified six metabolites in human liver microsomes, plasma, or urine: monomethylBPU, aminoBPU, G280, G308, G322, and G373. In patient urine, aminoBPU, G280, G308, and G322 collectively represented BPU dose. G280, G308, G322, and G373 showed minimal cytotoxicity. When BPU was given p.o. to mice in the presence and absence of the CYP3A and ABCG2 inhibitor, ritonavir, there was an increase in BPU plasma exposure and decrease in metabolite exposure but no overall change in cumulative exposure to BPU and the cytotoxic metabolites. Thus, we conclude that (a) CYP3A4 and CYP1A1 are the predominant cytochrome P450 enzymes that catalyze BPU metabolism, (b) BPU is metabolized to two cytotoxic and four noncytotoxic metabolites, and (c) ritonavir inhibits BPU metabolism to improve the systemic exposure to BPU without altering cumulative exposure to BPU and the cytotoxic metabolites.

  5. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis

    Science.gov (United States)

    Stegeman, Bernardine H; de Bastos, Marcos; Rosendaal, Frits R; van Hylckama Vlieg, A; Helmerhorst, Frans M; Stijnen, Theo

    2013-01-01

    Objective To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Design Systematic review and network meta-analysis. Data sources PubMed, Embase, Web of Science, Cochrane, Cumulative Index to Nursing and Allied Health Literature, Academic Search Premier, and ScienceDirect up to 22 April 2013. Review methods Observational studies that assessed the effect of combined oral contraceptives on venous thrombosis in healthy women. 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. The requirement for crude numbers did not allow adjustment for potential confounding variables. Results 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 1.9 and 3.7 per 10 000 woman years, in line with previously reported incidences of 1-6 per 10 000 woman 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, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk. Conclusion All combined oral contraceptives investigated in this analysis were

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

    Science.gov (United States)

    Bahamondes, Luis; Lira-Plascencia, Josefina; Martin, Ricardo; Marin, Victor; Makuch, Maria Y

    2015-01-01

    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 of COCs. To adequately counsel their patients regarding COC intake, OBGYNs must be updated regarding all aspects of COC use. PMID:25999766

  7. The effect of combined oral contraceptives and age on dysmenorrhoea: an epidemiological study.

    Science.gov (United States)

    Lindh, Ingela; Ellström, Agneta Andersson; Milsom, Ian

    2012-03-01

    Combined oral contraceptives (COCs) are widely advocated as treatment for primary dysmenorrhoea, but their efficacy has been questioned in a Cochrane review. The aim of this study was to evaluate COCs and the influence of age on the severity of dysmenorrhoea. Postal questionnaires regarding weight/height, contraception, pregnancy history and other reproductive health factors were sent to random samples of 19-year-old women born in 1962 (n = 656), 1972 (n = 780) and 1982 (n = 666) resident in the city of Gothenburg in 1981, 1991 and 2001. The responders were assessed again 5 years later at the age of 24 years. Current severity of dysmenorrhoea was measured on each occasion by a verbal multidimensional scoring system (VMS) and by a visual analogue scale (VAS). The severity of dysmenorrhoea was lower (PVMS score: a reduction of 0.3 units/VAS: a reduction of 9 mm, both PVMS score: a reduction of 0.1 units per 5 years, P< 0.0001/VAS: a reduction of 5 mm per 5 years, P< 0.0001). Childbirth also reduced the severity of dysmenorrhoea (VAS, P< 0.01 with a reduction of 7 mm). Women from the 82-cohort reported a greater severity of dysmenorrhoea compared with the 62 and 72 cohorts at both 19 and 24 years of age. In this longitudinal case-control study, COC use and increasing age, independent of each other, reduced the severity of dysmenorrhoea. COC use reduced the severity of dysmenorrhoea more than increasing age and childbirth. There was a trend over time regarding the severity of dysmenorrhoea where women from the 82-cohort reported a greater severity of dysmenorrhoea compared with the 62 and 72 cohorts.

  8. Venous thromboembolism and desogestrel- or gestodene-containing combination oral contraceptives: what are the facts?

    Science.gov (United States)

    1996-04-01

    The UK's prescription drug regulatory agency warned the public and health care providers about the possible increased risk of venous thromboembolism (VTE) among users of the combined oral contraceptives (OCs) containing desogestrel or gestodene. Data from three large not-yet-published studies served as the basis for the warning. The studies found about a 2-fold increased risk of VTE for these OC users when compared to users of OCs with other progestins. Yet the observational studies are subject to inherent biases (e.g., hospitalized cases and selection bias), which may explain the increased risk. Assuming the increased risk to be true, the risk of VTE is still lower than that linked to pregnancy (30 vs. 60 VTE cases per 100,000). The risk of VTE for users of OCs containing older progestins is about 15 VTE cases and that among healthy, nonpregnant, nonusers is about 4 VTE cases. The mortality risk associated with VTE among users of OCs containing desogestrel or gestodene is 1-1.5 deaths/1 million woman-years. The US Food and Drug Administration has examined the data and has concluded that the risk is not high enough to justify switching to other OCs or stopping use of OCs containing desogestrel or gestodene. It recommends that users of the OCs in question discuss the OCs with their providers and make an informed choice based on the benefits and risks and individual preferences. It might consider changes in labeling, but not pulling the OCs off the market. In Germany, women aged less than 30 were temporarily advised not to begin use of desogestrel- or gestodene-containing OCs. Women using them were advised to continue their use, however. The European Union announced that bias or chance could account for the findings and thus did not recommend changes in prescribing desogestrel- or gestodene-containing OCs.

  9. Use of Simulated Patients to Evaluate Combined Oral Contraceptive Dispensing Practices of Community Pharmacists

    Science.gov (United States)

    Obreli-Neto, Paulo Roque; Pereira, Leonardo Régis Leira; Guidoni, Camilo Molino; Baldoni, André de Oliveira; Marusic, Srecko; de Lyra-Júnior, Divaldo Pereira; de Almeida, Kelsen Luis; Pazete, Ana Claudia Montolezi; do Nascimento, Janaina Dutra; Kos, Mitja; Girotto, Edmarlon; Cuman, Roberto Kenji Nakamura

    2013-01-01

    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. PMID:24324584

  10. 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.

  11. Improving Control of Fusarium Wilt of Leguminous Plants by Combined Application of Biocontrol Agents

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    O.A. Abdul Wahid

    2006-12-01

    Full Text Available In dual culture tests, Trichoderma pseudokoningii and Bacillus subtilis parasitized and inhibited the growth of Fusarium oxysporum f. sp. fabae and of F. oxysporum f. sp. lupini, which cause wilt on broad bean and lupine respectively. When applied to the seeds of these crops in field experiments, both antagonists controlled wilt of broad bean and lupine (75.2% healthy plants. A mixture of both biocontrol agents was more effective than either agent used alone. Moreover, the biocontrol agents provided a higher percentage of healthy plants than a fungicide tested for comparison. Fresh filtrate of both antagonists was more effective in suppressing pathogen growth than stored filtrate.

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

    OpenAIRE

    Mercedes eFernandez y Mostajo; Wil evan der Reijden; Mark eBuijs; Wouter eBeertsen; Fridus evan der Weijden; Wim eCrielaard; Egija eZaura

    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. Material and methods: In vitro, 16 oral bacterial strains w...

  13. In Vitro Synergistic Effect of Psidium guineense (Swartz in Combination with Antimicrobial Agents against Methicillin-Resistant Staphylococcus aureus Strains

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    Tiago Gomes Fernandes

    2012-01-01

    Full Text Available The aim of this study was to evaluate the antimicrobial activity of aqueous extract of Psidium guineense Swartz (Araçá-do-campo and five antimicrobials (ampicillin, amoxicillin/clavulanic acid, cefoxitin, ciprofloxacin, and meropenem against twelve strains of Staphylococcus aureus with a resistant phenotype previously determined by the disk diffusion method. Four S. aureus strains showed resistance to all antimicrobial agents tested and were selected for the study of the interaction between aqueous extract of P. guineense and antimicrobial agents, by the checkerboard method. The criteria used to evaluate the synergistic activity were defined by the fractional inhibitory concentration index (FICI. All S. aureus strains were susceptible to P. guineense as determined by the microdilution method. The combination of the P. guineense extract with the antimicrobial agents resulted in an eight-fold reduction in the MIC of these agents, which showed a FICI ranging from 0.125 to 0.5, suggesting a synergistic interaction against methicillin-resistant Staphylococcus aureus (MRSA strains. The combination of the aqueous extract of P. guineense with cefoxitin showed the lowest FICI values. This study demonstrated that the aqueous extract of P. guineense combined with beta lactamics antimicrobials, fluoroquinolones, and carbapenems, acts synergistically by inhibiting MRSA strains.

  14. Discovery of WQ-3810: Design, synthesis, and evaluation of 7-(3-alkylaminoazetidin-1-yl)fluoro-quinolones as orally active antibacterial agents.

    Science.gov (United States)

    Itoh, Kenji; Kuramoto, Yasuhiro; Amano, Hirotaka; Kazamori, Daichi; Yazaki, Akira

    2015-10-20

    Novel 7-(3-alkylaminoazetidin-1-yl)fluoroquinolones were designed, synthesized, and evaluated for their antibacterial activities and oral absorption rates. Against Gram-negative bacteria, 10a-e, which have various alkyl groups containing different numbers of carbon atoms (C0-C3) at the C-7 alkylaminoazetidine position, showed potent and similar antibacterial activities, whereas the activity of 10f (C4, t-Bu) was significantly lower than those of 10a-e. Conversely, the oral absorption rates of 10a-e in rats increased depending on the number of carbon atoms in the alkyl groups; 10d (C3, n-Pr) and 10e (C3, i-Pr) had high oral absorption rates (>90% at 10 mg/kg). These results demonstrated that the introduction of alkyl groups onto C-7 aminoazetidine is useful for the improvement of the oral absorption rates of these drugs while maintaining their antibacterial activities. As a conclusion, from this series of fluoroquinolones, WQ-3810 (10e), having 3-isopropylaminoazetidine as the C-7 substituent, was identified as an orally active antibacterial agent with a potent in vitro activity.

  15. Combined Oral Medroxyprogesterone/Levonorgestrel-Intrauterine System Treatment for Women With Grade 2 Stage IA Endometrial Cancer.

    Science.gov (United States)

    Hwang, Ji Young; Kim, Da Hee; Bae, Hyo Sook; Kim, Mi-La; Jung, Yong Wook; Yun, Bo Seong; Seong, Seok Ju; Shin, Eunah; Kim, Mi Kyoung

    2017-05-01

    The aim of this study was to evaluate the oncologic and pregnancy outcomes of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment in young women with grade 2-differentiated stage IA endometrial adenocarcinoma who wish to preserve fertility. We retrospectively reviewed the medical records of patients with grade 2 stage IA endometrial adenocarcinoma who had received fertility-sparing treatment at CHA Gangnam Medical Center between 2011 and 2015. All of the patients were treated with combined oral MPA (500 mg/d)/LNG-IUS, and follow-up dilatation and curettage were performed every 3 months. A total of 5 patients were included in the study. The mean age was 30.4 ± 5.3 years (range, 25-39 years). After a mean treatment duration of 11.0 ± 6.2 months (range, 6-18 months), complete response (CR) was shown in 3 of the 5 patients, with partial response (PR) in the other 2 patients. One case of recurrence was reported 14 months after achieving CR. This patient was treated again with combined oral MPA/LNG-IUS and achieved CR by 6 months. The average follow-up period was 44.4 ± 26.2 months (range, 12-71 months). There were no cases of progressive disease. No treatment-related complications arose. Combined oral MPA/LNG-IUS treatment is considered to be a reasonably effective fertility-sparing treatment of grade 2 stage IA endometrial cancer. Although our results are encouraging, it is preliminary and should be considered with experienced oncologists in well-defined protocol and with close follow-up.

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

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    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.

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

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    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.

  18. Sexual Dysfunction in Two Types of Hormonal Contraception: Combined Oral Contraceptives versus Depot Medroxyprogesterone Acetate

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    Nourossadat Kariman

    2017-01-01

    Full Text Available Background & aim: Sexual health is an essential element of quality of life, affecting both physical and psychological domains. Hormones used in contraceptive methods have contradictory effects on sexual function. In this study, we aimed to compare sexual function in women using combined oral contraceptives (COC and depot medroxyprogesterone acetate (DMPA, referred to healthcare centers affiliated to Shahid Beheshti University of Medical Sciences in Tehran, Iran in 2013. Methods: This descriptive, comparative study was performed on 240 women (n=120 per group, selected through multistage sampling in Tehran, Iran. A questionnaire consisting of three parts, General Health Questionnaire (GHQ-28, demographic characteristics, and Female Sexual Function Index (FSFI, was completed through interviews. For data analysis, descriptive statistics were calculated, and independent t-test, Mann-Whitney test, Chi-square, and Fisher's exact test were performed, using SPPS version 16. P-value less than 0.05 was considered statistically significant. Results: The mean age at marriage in women using DMPA was lower than those using COC (18.55±3.61 vs. 19.92±3.98 years. Based on the findings, the menstrual status in the majority of DMPA users was irregular (46.7% in DMPA group vs. 8.3% in COC group. The difference in sexual function between the COC and DMPA groups was significant. Sexual arousal and lubrication were more favorable in the COC group in comparison with the DMPA group; also, pain in this group was lower than the DMPA group. Scores of total sexual function (27.35±5.22 in DMPA group vs. 29.15±6.13 in COC group, sexual arousal (4.11±0.90 in DMPA group vs. 4.51±1.39 in COC group, and vaginal lubrication (4.82±1.30 in DMPA group vs. 5.26±1.35 in COC group were lower in the DMPA group, compared to the COC group. Pain scores (4.91±1.25 in DMPA group vs. 5.28±1.19 in COC group were higher in the DMPA group in comparison with the COC group (P

  19. Aderência de diabéticos ao tratamento medicamentoso com hipoglicemiantes orais Adhesión de diabéticos al tratamiento con hipoglucemiantes orales Adherence of diabetics patient to pharmacological treatment with oral hypoglycemic agents

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    Márcio Flávio Moura de Araújo

    2010-06-01

    Full Text Available Objetivou-se identificar a adesão de diabéticos de Sobral CE ao tratamento farmacológico com hipoglicemiantes orais. Investigaram-se 79 diabéticos de seis unidades básicas de saúde de Sobral CE mediante visitas domiciliárias durante o período de março a junho de 2007. Para coleta de dados utilizou-se um formulário estruturado e a aplicação do Teste de Morisky e Green adaptado. Um pouco mais da metade dos estudados, 54,5%, referiu não ter o cuidado de cumprir o horário de ingestão dos fármacos preestabelecido; a maioria não se esquece de tomar a medicação (66%. Ademais, 90% dos investigados apresentam sentimento de pesar ao deixar de tomar os hipoglicemiantes orais. Identificou-se que 54,4% e 45,5% eram menos aderentes e mais aderentes à terapia medicamentosa com hipoglicemiantes orais, respectivamente. A adesão à terapia farmacológica com hipoglicemiantes orais é fundamental para um bom controle glicêmico e a prevenção de complicações micro e macrovasculares.El objetivo fue identificar la adhesión de diabéticos de Sobral CE, Brasil, al tratamiento farmacológico con agentes hipoglucemiantes orales.Fueron investigados 79 diabéticos de seis unidades básicas de salud de Sobral-CE, Brasil, mediante visitas domiciliarias durante el período de marzo a junio de 2007. Para la recolecta de datos fue utilizado un cuestionario estructurado y la aplicación del Test de Morisky y Green adaptado. Poco más de la mitad de los estudiados, 54.5%, dijo no tener cuidado de cumplir con el horario preestablecido para la ingestión de los fármacos; la mayoría no se olvida de tomar la medicación (66%. Además, el 90% de los investigados presentó sentimientos de aflicción al dejar de tomar los hipoglucemiantes orales. Se identificó que el 54.4% y el 45.5% presentaban menos adherencia y mayor adherencia respectivamente - a la terapia con fármacos hipoglucemiantes orales. .La adhesión a la terapia farmacológica con

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

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    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. Oral misoprostol in the prevention of uterine bleeding after surgical evacuation of first trimester abortion: a comparative study of three uterotonic agents.

    Science.gov (United States)

    Aramide, T M; Olusegun, A K; Akinfolarin, A C; Oriola, D F

    2014-01-01

    This comparative study was aimed at determining the effectiveness of oral Misoprostol compared with intravenous Ergometrine and intravenous Oxytocin in reducing vaginal bleeding following surgical evacuation for first trimester abortions. This was a single-blind placebo-controlled study in which patients with first trimester uncomplicated abortions were divided into three groups using computer-generated randomization table. The first group was administered oral Misoprostol, the second group had intravenous Ergometrine, and the third group was administered intravenous Oxytocin. The uterotonic agents were administered before the surgical evacuation was carried out. There was statistically significant reduction in blood loss after the evacuation in the Misoprostol group ( P Misoprostol group (2.00 ± 0.86) compared with 4.43 ± 0.92 and 4.64 ± 1.06 days in the Ergometrine and Oxytocin groups, respectively ( P Misoprostol and Ergometrine groups (60.7% and 57.1%, respectively) compared with the Oxytocin group. Oral Misoprostol appeared to demonstrate superior efficacy in reducing uterine bleeding after surgical evacuation, compared to the other commonly used uterotonic agents.

  2. Canagliflozin: Efficacy and Safety in Combination with Metformin Alone or with Other Antihyperglycemic Agents in Type 2 Diabetes

    OpenAIRE

    Qiu, Rong; Balis, Dainius; Capuano, George; Xie, John; Meininger, Gary

    2016-01-01

    Metformin is typically the first pharmacologic treatment recommended for type 2 diabetes mellitus (T2DM), but many patients do not achieve glycemic control with metformin alone and eventually require combination therapy with other agents. Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was assessed in a comprehensive Phase 3 clinical development program consisting of ~10,000 participants, of which ~80% were on background therapy that consisted of metformin alone or in comb...

  3. An agent strategy for automated stock market trading combining price and order book information

    NARCIS (Netherlands)

    Silaghi, G.; Robu, V.

    2005-01-01

    This paper proposes a novel automated agent strategy for stock market trading, developed in the context of the Penn-Lehman automated trading (PLAT) simulation platform by Kearns, M., and Ortiz, L., (2003). We provide a comprehensive experimental validation of our strategy using historic order book d

  4. Percutaneous exposure to the nerve agent VX: Efficacy of combined atropine, obidoxime and diazepam treatment

    NARCIS (Netherlands)

    Joosen, M.J.A.; Schans, M.J. van der; Helden, H.P.M. van

    2010-01-01

    The nerve agent VX is most likely to enter the body via liquid contamination of the skin. After percutaneous exposure, the slow uptake into the blood, and its slow elimination result in toxic levels in plasma for a period of several hours. Consequently, this has implications for the development of t

  5. Isobolographic analyses of the gabapentin-metamizol combination after local peripheral, intrathecal and oral administration in the rat.

    Science.gov (United States)

    Ortega-Varela, Luis F; Herrera, Jorge E; Caram-Salas, Nadia L; Rocha-González, Héctor I; Granados-Soto, Vinicio

    2007-01-01

    This study was designed to evaluate the possible antinociceptive interaction between gabapentin and metamizol on formalin-induced nociception. Gabapentin, metamizol or a fixed dose-ratio combination of both drugs were assessed after local peripheral, intrathecal and oral administration in rats. Isobolographic analyses were employed to define the nature of the interaction between drugs. Gabapentin, metamizol and gabapentin-metamizol combinations yielded a dose-dependent antinociceptive effect when administered by the three different routes. ED30 values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED30 values for the combination estimated from the isobolograms were 21.11 +/- 1.17 microg/paw, 104.6 +/- 5.5 microg/rat and 78.8 +/- 5.5 mg/kg for the local peripheral, intrathecal and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED30 values which were 11.3 +/- 1.5 microg/paw, 36.8 +/- 3.1 microg/rat and 15 +/- 1.2 mg/kg indicating a synergistic interaction. Systemic administration resulted in the highest synergism. Data confirm that low doses of the gabapentin and metamizol can interact synergistically to reduce formalin-induced nociceptive behavior suggesting that this combination could be useful to treat inflammatory pain in humans. 2007 S. Karger AG, Basel

  6. Use of albendazole sulfoxide, albendazole sulfone, and combined solutions as scolicidal agents on hydatid cysts ( in vitro study)

    Institute of Scientific and Technical Information of China (English)

    Gokhan Adas; Soykan Arikan; Ozgur Kemik; Ali Oner; Nilgun Sahip; Oguzhan Karatepe

    2009-01-01

    AIM: To establish which scolicidal agents are superior and more suitable for regular use.METHODS: Echinococcus granulosus protoscoleces were obtained from 25 patients with liver hydatid cysts. Various concentrations of albendazole sulfone,albendazole sulfoxide, and albendazole sulfone and albendazole sulfoxide mixed together in concentrations of 50 μg/mL, and H2O2 in a concentration of 4%, NaCl 20%, and 1.5% cetrimide-0.15% chlorhexidine (10% Savlon-Turkey) were used to determine the scolicidal effects. Albendazole (ABZ) derivatives and other scolicidal agents were applied to a minimum of 100 scoleces for 5 and 10 min. The degree of viability was calculated according to the number of living scolices per field from a total of 100 scolices observed under the microscope.RESULTS: After 5 min, ABZ sulfone was 97.3% effective, ABZ sulfoxide was 98.4% effective, and the combined solution was 98.6% effective. When sulfone, sulfoxide and the combined solutions were compared,the combined solution seemed more effective than sulfone. However, there was no difference when the combined solution was compared with sulfoxide. After 10 min, hypertonic salt water, sulfone, sulfoxide, and the combined solution compared to other solutions looked more effective and this was statistically significant on an advanced level. When sulfone,sulfoxide, and the combined solutions were compared with each other, the combined solution appeared more effective than sulfone. When the combined solution was compared with sulfoxide, there was no difference.CONCLUSION: Despite being active, ABZ metabolites did not provide a marked advantage over 20% hypertonic saline. According to these results, we think creating a newly improved and more active preparation is necessary for hydatid cyst treatment.

  7. 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.

  8. From Mouth to Model: Combining in vivo and in vitro Oral Biofilm Growth.

    Science.gov (United States)

    Klug, Barbara; Santigli, Elisabeth; Westendorf, Christian; Tangl, Stefan; Wimmer, Gernot; Grube, Martin

    2016-01-01

    Background: 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. Aims: 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. Methods: 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 h. 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 h 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 1 (T1), 24 (T2), and 48 h (T3) of incubation. Bacterial diversity at T0 and T3 was compared with 454-pyrosequencing. Fluorescence in situ hybridization (FISH) 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. Results: 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

  9. From Mouth to Model: Combining in vivo and in vitro Oral Biofilm Growth

    Science.gov (United States)

    Klug, Barbara; Santigli, Elisabeth; Westendorf, Christian; Tangl, Stefan; Wimmer, Gernot; Grube, Martin

    2016-01-01

    Background: 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. Aims: 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. Methods: 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 h. 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 h 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 1 (T1), 24 (T2), and 48 h (T3) of incubation. Bacterial diversity at T0 and T3 was compared with 454-pyrosequencing. Fluorescence in situ hybridization (FISH) 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. Results: 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

  10. The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model.

    Science.gov (United States)

    Ruda, James M; Beus, Kirt S; Hollenbeak, Christopher S; Wilson, Ronald P; Stack, Brendan C

    2006-09-01

    To determine whether oral administration of fusaric acid (FA) inhibits tumor growth in an animal model of head and neck cancer (HNSCC). In vivo murine model, two arm controlled study. Thirty-eight (38) 5-week-old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n = 19) or a sterile saline group (n = 19). A left, lateral flank subcutaneous injection of 2.0 x 10(6) UM-SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (> or =65 mm3), and tumor volumes were recorded after tumor xenografting. Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p = 0.00451). By Day 9, all mice in the control group had developed measurable tumors in comparison to only 78% of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p < 0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p = 0.0142). Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model. As an orally active agent, it may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.

  11. Event-triggered nonlinear consensus in directed multi-agent systems with combinational state measurements

    Science.gov (United States)

    Li, Huaqing; Chen, Guo; Xiao, Li

    2016-10-01

    Event-triggered sampling control is motivated by the applications of embedded microprocessors equipped in the agents with limited computation and storage resources. This paper studied global consensus in multi-agent systems with inherent nonlinear dynamics on general directed networks using decentralised event-triggered strategy. For each agent, the controller updates are event-based and only triggered at its own event times by only utilising the locally current sampling data. A high-performance sampling event that only needs local neighbours' states at their own discrete time instants is presented. Furthermore, we introduce two kinds of general algebraic connectivity for strongly connected networks and strongly connected components of the directed network containing a spanning tree so as to describe the system's ability for reaching consensus. A detailed theoretical analysis on consensus is performed and two criteria are derived by virtue of algebraic graph theory, matrix theory and Lyapunov control approach. It is shown that the Zeno behaviour of triggering time sequence is excluded during the system's whole working process. A numerical simulation is given to show the effectiveness of the theoretical results.

  12. Extended cycle combined oral contraceptives and prophylactic frovatriptan during the hormone-free interval in women with menstrual-related migraines.

    Science.gov (United States)

    Coffee, Andrea L; Sulak, Patricia J; Hill, Alexandria J; Hansen, Darci J; Kuehl, Thomas J; Clark, Jeffrey W

    2014-04-01

    Migraine headaches are a significant problem for American women with many of them suffering from headaches around the time of their menstrual cycle. Women taking oral contraceptives in the standard 21/7 cycle regimen often suffer from headaches around the time of the hormone free intervals (HFIs) as well. Extended oral contraceptive regimens have been shown to decrease the frequency, but not eliminate these headaches. This study is a double-blind, randomized, placebo-controlled pilot study of participants with menstrual-related migraines (MRMs) who were initiated on extended combined oral contraceptives and given frovatriptan prophylactically during HFIs. Participants having spontaneous menstrual cycles or taking daily combined oral contraceptives in a 21/7 regimen with MRMs were placed on a contraceptive containing levonorgestrel and ethinyl estradiol. Analyses compared headache scores during pre-study baseline cycles to those in a 168-day extended regimen with placebo versus frovatriptan treatments during HFIs. Daily headache scores decreased (p=0.034) from 1.29 ± 0.10 during pre-study cycles to 1.10 ± 0.14 during extended combined oral contraceptive use. Frovatriptan blocked the increase in headache score over the placebo during HFIs. However, following the withdrawal of frovatriptan, headache scores increased (p>0.01) despite resuming combined oral contraceptive use. Extended combined oral contraceptive regimen reduces MRM severity. Frovatriptan prevents headaches during HFIs, but is associated with new headache symptoms when withdrawn.

  13. Successful treatment of oral verrucous hyperplasia with photodynamic therapy combined with cryotherapy--report of 3 cases.

    Science.gov (United States)

    Chang, Yu-Chao; Yu, Chuan-Hang

    2014-06-01

    Our previous study showed successful treatment of a large oral verrucous hyperplasia (OVH) with topical 5-aminolevulinic acid-mediated photodynamic therapy combined with cryotherapy (ALA-PDT). In this case series, we extended this combined method for another three OVH lesions in three different patients. The clinical procedure was conducted as follows: the OVH lesions were irradiated with a 635-nm laser 1.5h after topical application of 20% ALA on the lesion for a total of 1000 s, which consisted of five 3-min and one 100-s irradiations separated by five 3-min rests. Cryogun cryotherapy was then performed on the lesion after ALA-PDT. The tumor was cleared after 1-6 treatments. No recurrence of the lesion was found after a follow-up period of 6-24 months. We suggest that our combined treatment protocol may be effective in treating OVH lesions. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. A numerical study of combined use of two biocontrol agents with different biocontrol mechanisms in controlling foliar pathogens.

    Science.gov (United States)

    Xu, X-M; Jeffries, P; Pautasso, M; Jeger, M J

    2011-09-01

    Effective use of biocontrol agents is an important component of sustainable agriculture. A previous numerical study of a generic model showed that biocontrol efficacy was greatest for a single biocontrol agent (BCA) combining competition with mycoparasitism or antibiosis. This study uses the same mathematical model to investigate whether the biocontrol efficacy of combined use of two BCAs with different biocontrol mechanisms is greater than that of a single BCA with either or both of the two mechanisms, assuming that two BCAs occupy the same host tissue as the pathogen. Within the parameter values considered, a BCA with two biocontrol mechanisms always outperformed the combined use of two BCAs with a single but different biocontrol mechanism. Similarly, combined use of two BCAs with a single but different biocontrol mechanism is shown to be far less effective than that of a single BCA with both mechanisms. Disease suppression from combined use of two BCAs was very similar to that achieved by the more efficacious one. As expected, a higher BCA introduction rate led to increased disease suppression. Incorporation of interactions between two BCAs did not greatly affect the disease dynamics except when a mycoparasitic and, to a lesser extent, an antibiotic-producing BCA was involved. Increasing the competitiveness of a mycoparasitic BCA over a BCA whose biocontrol mechanism is either competition or antibiosis may lead to improved biocontrol initially and reduced fluctuations in disease dynamics. The present study suggests that, under the model assumptions, combined use of two BCAs with different biocontrol mechanisms in most cases only results in control efficacies similar to using the more efficacious one alone. These predictions are consistent with published experimental results, suggesting that combined use of BCAs should not be recommended without clear understanding of their main biocontrol mechanisms and relative competitiveness, and experimental evaluation.

  15. 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.

  16. Ultrasonograpy of VX-2 Liver Tumor in Rabbit Treated by High Intensity Focused Ultrasound Combined with Microbubble Contrast Agent

    Science.gov (United States)

    Xiaojuan, Ji; Jinqing, Li; Zhibiao, Wang; Jianzhong, Zou; Wenzhi, Chen; Jin, Bai

    2007-05-01

    Objective: To assess the value of sonographic appearance and to investigate the sonographic character of VX-2 liver tumor in rabbit treated by high intensity focused ultrasound (HIFU) combined with microbubble contrast agent. Methods: Forty-five rabbits bearing VX-2 tumors were randomly averagely assigned into three groups. In group A irradiation was sustained until the target region became hyperechoic. In group B therapy was stopped as soon as hyperecho occurred, and in group C irradiation time was prolonged to ensure the occurrence of coagulation necrosis. Results: Exposure duration for tumors treated purely with HIFU was the longest, whilst the use of microbubble contrast agent combined with HIFU shortened the exposure duration significantly. The gross examination and ultrasonogram coagulation necrosis area measurements correlated strongly (r=0.986,P<0.05) in the microbubble-enhanced HIFU group. Conclusion: It was feasible to enhance HIFU therapy with microbubble contrast agent. The characteristic change in the ultrasound images made it possible to assess the enhanced HIFU therapeutic efficacy in order to adjust the treatment program.

  17. Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents.

    Science.gov (United States)

    Koto, Kazutaka; Murata, Hiroaki; Kimura, Shinya; Horie, Naoyuki; Matsui, Takaaki; Nishigaki, Yasunori; Ryu, Kazuteru; Sakabe, Tomoya; Itoi, Megumi; Ashihara, Eishi; Maekawa, Taira; Fushiki, Shinji; Kubo, Toshikazu

    2010-07-01

    Third-generation bisphosphonates are known to inhibit bone resorption and also appear to exhibit direct anti-tumour activity. We previously reported that third-generation bisphosphonates such as zoledronic acid (ZOL) have a direct antitumour effect, and synergistically augment the effects of antitumor agents in osteosarcoma cells. There has been no report on the antitumor effect of ZOL against soft tissue sarcoma. The aim of this study was to evaluate the antitumor effect of this drug on a human fibrosarcoma cell line, in terms of proliferation and apoptosis, and, moreover, to evaluate the combined effects of ZOL with other antitumor drugs against the human fibrosarcoma cell line. HT1080 cells were treated with ZOL at various concentrations up to 10 microM, and then cell proliferation, cell cycle, nuclear morphology, and Western blot analyses were performed to study the antitumor effects of ZOL alone, and, moreover, HT1080 cells were treated with ZOL and other anticancer drugs such as paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, cisplatin, or methotrexate to investigate the combined effects using proliferation and cell cycle analyses. We found that ZOL strongly inhibited in vitro proliferation, arrested the cell cycle between S and G2/M phases, and induced the apoptosis of human fibrosarcoma cells. Moreover, ZOL augmented the effect of antitumor agents when administered concurrently with paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, and cisplatin in human fibrosarcoma cells. The treatment of fibrosarcoma with ordinary antitumor drugs is not fully effective. These findings suggest that ZOL directly affects the proliferation and survival of fibrosarcoma cells, and that the combined administration of ZOL with other antitumor agents may improve the efficacy of fibrosarcoma treatment. These results support the possibility that their combined use could be beneficial in the treatment of patients not only with

  18. Combined oral treatment with racemic and meso-2,3-dimercaptosuccinic acid for removal of mercury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kostial, K.; Restek-Samarzija, N.; Blanusa, M.; Piasek, M. [Inst. for Medical Research and Occupational Health, Zagreb (Croatia); Mones, M.M. [Vanderbilt Univ., Dept. of Chemistry, Nashville, TN (United States); Singh, P.K. [Ellington Agriculture Center, Tennessee Dept. of Agriculture, Food Residue and Toxicology Lab., Nashville, TN (United States)

    1997-11-01

    Racemic dimercaptosuccinic acid (DMSA) was found more efficient than the meso-isoform in enhancing the removal of mercury in rats. However, racemic-DMSA has recently been found more toxic. The efficiency of combined oral treatment with the two isoforms of DMSA for removal of mercury has now been evaluated. Female albino rats were treated orally for four days with meso- (M) and/or racemic- (R) DMSA (1 mmol/kg each), five days after a single intraperitoneal administration of {sup 203}Hg with 0.5 mg HgCl{sub 2}/kg. The animals were divided into six groups according to the number of treatments with each isomer: control (untreated), 4M, IR+3M, 2R+2M, 3R+1M, and 4R. Whole body, kidney, liver and brain mercury contents were measured nine days after {sup 203}Hg administration. In all treated groups retention in the whole body and kidneys was greatly reduced. The groups treated with racemic-DMSA, regardless of the number of doses, showed a greater removal of mercury than the group treated with meso-DMSA alone (4M). All treatments were less efficient in reducing liver retention, and the brain retention was not affected. It was concluded that even a single application of the more toxic racemic-DMSA during a four-day oral treatment regimen is sufficient to improve the removal by meso-DMSA of mercury from rats. (au). 8 refs.

  19. The influence of excipients on physical and pharmaceutical properties of oral lyophilisates containing a pregabalin-acetaminophen combination.

    Science.gov (United States)

    Chiriac, Aurica P; Diaconu, Alina; Nita, Loredana E; Tudorachi, Nita; Mititelu-Tartau, Liliana; Creteanu, Andreea; Dragostin, Oana; Rusu, Daniela; Popa, Gratiela

    2017-05-01

    The purpose of the study was to investigate and characterize the oral lyophilisates containing the pregabalin-acetaminophen drug combination and as xcipients mannitol with microcrystalline cellulose or hydroxypropyl methylcellulose, in order to conclude upon drug-excipient interactions and their stability implications, impact of excipients on drug release and on the physicochemical and mechanical properties of the pharmaceutical formulations. The oral tablets were made by using a Christ freeze-dryer alpha 2-4-LSC lyophilizer, and evaluated for stability, drug-excipient compatibility and homogeneity of the prepared pharmaceutical formulations. The formulations were evaluated for in vivo absorption in rabbits by histopathological exams. FTIR and thermogravimetric analyses, DLS technique, SEM and NIR-CI studies confirmed the compatibility between compounds. From the determined physical and biochemical parameters of the formulations it was established that they are stable, homogeneous, and meet the conditions for orally disintegrating tablets. In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the 'codrug' complex, which do not affect the release of the bioactive compounds.

  20. Distributed Optimal Economic Dispatch Based on Multi-Agent System Framework in Combined Heat and Power Systems

    Directory of Open Access Journals (Sweden)

    Yu-Shuai Li

    2016-10-01

    Full Text Available In this paper, a novel distributed method is presented to solve combined heat and power economic dispatch problem, which is formulated as a distributed coupled optimization problem. The optimization goal is achieved by establishing two modified consensus protocols with two corresponding feedback parts while satisfying the electrical and heat supply–demand balance. Moreover, an alternating iterative method is proposed to handle the heat-electrical coupling problem existed in the objective function and the feasible operating regions. In addition, the proposed distributed method is implemented by a multi-agent system framework, which only requires local information exchange among neighboring agents. Simulation results obtained on a 16-bus test system are provided to illustrate the effectiveness of the proposed distributed method.

  1. 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

  2. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

    Science.gov (United States)

    Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

    2017-02-01

    We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

  3. 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.

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

    Science.gov (United States)

    Oviedo, Adriana; Díaz, Mirna; Valenzuela, María Laura; Vidal, Victoria; Racca, Liliana; Bottai, Hebe; Priore, Graciela; Peluffo, Graciela; Di Bartolomeo, Susana; Cabral, Graciela; Toca, María del Carmen

    2016-01-01

    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. PMID:28009823

  5. Assessments of low emission asphalt mixtures produced using combinations of foaming agents

    Science.gov (United States)

    Mohd Hasan, Mohd Rosli

    The asphalt foaming techniques have been used over the last couple of decades as an alternative to the traditional method of preparing asphalt mixtures. Based on positive feedback from the industry, this study was initiated to explore and evaluate the performance of the Warm Mix Asphalt (WMA) mixture produced through a foaming process using physical and chemical foaming agents, which are ethanol and sodium bicarbonate (NaHCO3), respectively. The success of this project may lead to new theories and provide an environmentally friendly technique to produce asphalt mixtures. This may advance the understanding of the foaming process and improve the performance of WMA to support sustainable development. Theoretically, ethanol can function in the same manner as water but requires less energy to foam due to its lower boiling point, 78°C. During the asphalt foaming process, numerous bubbles were generated by the vaporized ethanol, which significantly increased the volume of the asphalt binder, hence the coating potential of aggregates improves. The sodium bicarbonate was incorporated to enhance the quantity of bubbles and its stability. Therefore, understanding foaming agents, their solubility, chemical reactions, chemical function groups and rheological properties of the foamed binder are essential to help control the foam structure and final properties of the foamed WMA mixture. In order to understand the overall performance of newly developed foaming WMA, this material was evaluated for moisture susceptibility, rutting potential, and resistance to fracture and thermal cracking. The coatability, workability and compactability of foamed asphalt mixtures during production were also evaluated. Based on the results, it was found that the newly proposed foaming WMA has high potential to promote sustainable development by lowering the energy consumption and impacts on the environment. The ethanol is efficient in lowering the viscosity of asphalt binders, enhancing the

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

    Directory of Open Access Journals (Sweden)

    P Pallavee

    2013-01-01

    Full Text Available 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.

  7. 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...

  8. Cost-effectiveness study of oral hypoglycemic agents in the treatment of outpatients with type 2 diabetes attending a public primary care clinic in Mexico City

    Directory of Open Access Journals (Sweden)

    Cárdenas-Elizalde MR

    2012-03-01

    Full Text Available Christian Díaz de León-Castañeda, Marina Altagracia-Martínez, Jaime Kravzov-Jinich, Ma del Rosario Cárdenas-Elizalde, Consuelo Moreno-Bonett, Juan Manuel Martínez-NúñezDepartment of Biological Systems and Health Care, Biological and Health Sciences Division, Universidad Autónoma Metropolitana-Xochimilco, Mexico DF, MexicoIntroduction: Worldwide, diabetes mellitus presents a high burden for individuals and society. In Latin America, many people with diabetes have limited access to health care, which means that indirect costs may exceed direct health care cost. Diabetes is Mexico's leading cause of death.Purpose: To evaluate the cost-effectiveness ratios of the most used oral hypoglycemic agents (OHA in the treatment of outpatients with type 2 diabetes attending a public primary care clinic in Mexico City.Design: A cross-sectional and analytic study was conducted in Mexico City.Methodology: Twenty-seven adult outpatients with type 2 diabetes who were treated either with metformin or glibenclamide were included. Acarbose was used as an alternative strategy. The study was carried out from the perspective of Mexican society. Direct medical and nonmedical costs as well as indirect costs were evaluated using a structured questionnaire. Efficacies of all drug treatments were evaluated retrospectively. A systematic search was conducted to select published randomized clinical trials based on predetermined inclusion criteria, and treatment success was defined as glycosylated hemoglobin factor ≤ 7%. Efficacy data of each drug and/or combination were analyzed using meta-analysis. The Monte Carlo Markov model was used. Quality-adjusted life-years (QALY were used as the unit of effectiveness; incremental and sensitive analyses were performed and a 5% discount rate was calculated. A hypothetical cohort of 10,000 patients was modeled.Results: The odds ratios of the success of each drug treatment were obtained from the meta-analyses, and were the

  9. Cost-effectiveness study of oral hypoglycemic agents in the treatment of outpatients with type 2 diabetes attending a public primary care clinic in Mexico City

    Science.gov (United States)

    de León-Castañeda, Christian Díaz; Altagracia-Martínez, Marina; Kravzov-Jinich, Jaime; Cárdenas-Elizalde, Ma del Rosario; Moreno-Bonett, Consuelo; Martínez-Núñez, Juan Manuel

    2012-01-01

    Introduction Worldwide, diabetes mellitus presents a high burden for individuals and society. In Latin America, many people with diabetes have limited access to health care, which means that indirect costs may exceed direct health care cost. Diabetes is Mexico’s leading cause of death. Purpose To evaluate the cost-effectiveness ratios of the most used oral hypoglycemic agents (OHA) in the treatment of outpatients with type 2 diabetes attending a public primary care clinic in Mexico City. Design A cross-sectional and analytic study was conducted in Mexico City. Methodology Twenty-seven adult outpatients with type 2 diabetes who were treated either with metformin or glibenclamide were included. Acarbose was used as an alternative strategy. The study was carried out from the perspective of Mexican society. Direct medical and nonmedical costs as well as indirect costs were evaluated using a structured questionnaire. Efficacies of all drug treatments were evaluated retrospectively. A systematic search was conducted to select published randomized clinical trials based on predetermined inclusion criteria, and treatment success was defined as glycosylated hemoglobin factor ≤ 7%. Efficacy data of each drug and/or combination were analyzed using meta-analysis. The Monte Carlo Markov model was used. Quality-adjusted life-years (QALY) were used as the unit of effectiveness; incremental and sensitive analyses were performed and a 5% discount rate was calculated. A hypothetical cohort of 10,000 patients was modeled. Results The odds ratios of the success of each drug treatment were obtained from the meta-analyses, and were the following: 5.82 (glibenclamide), 3.86 (metformin), 3.5 (acarbose), and 6.76 (metformin–glibenclamide). The cost-effectiveness ratios found were US$272.63/QALY (glibenclamide), US$296.48/QALY (metformin), and US$409.86/QALY (acarbose). Sensitivity analysis did not show changes for the most cost-effective therapy when the effectiveness probabilities or

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

    NARCIS (Netherlands)

    Fernandez y Mostajo, M.; van der Reijden, W.A.; Buijs, M.J.; Beertsen, W.; van der Weijden, F.; Crielaard, W.; Zaura, E.

    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 o

  11. [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.

  12. Impact of compliance with oral antihyperglycemic agents on health outcomes in type 2 diabetes mellitus: a focus on frequency of administration.

    Science.gov (United States)

    Guillausseau, Pierre-Jean

    2005-01-01

    Compliance with treatment is crucial to the optimal management of any chronic disease. Non-compliance with antihyperglycemic treatment is clearly a significant issue for patients with type 2 diabetes mellitus as it decreases the efficacy of the treatment and increases the risk of developing microvascular and macrovascular complications, therefore increasing the human and economic costs of this disease. The effect of low compliance on metabolic control has been shown to represent an increase of up to 1.4% in glycosylated hemoglobin. Achieving optimal compliance is therefore a therapeutic objective of prime importance. Many factors have been cited as contributing to poor compliance. Some of these, such as age, severe complications and disabilities, and social, educational, and financial difficulties, affect compliance with treatment in quite a significant manner, but are not modifiable by the healthcare provider. Other factors, such as the number of tablets per dose and polymedication, are modifiable but do not appear to be of major importance, whereas the frequency of administration is both an important and a modifiable factor affecting compliance with treatment. One strategy for optimization of compliance involves treatment of type 2 diabetes using oral antihyperglycemic agents with once-daily formulations. Recent data indicate that reducing the daily administration frequency of oral antihyperglycemic agents improves compliance with treatment and consequently metabolic control. Therefore, optimization of treatment through a reduction in the frequency of antihyperglycemic administration could be a valuable weapon in the battle to improve health outcomes and reduce the burden of type 2 diabetes.

  13. 口腔微生物生物膜分散物质的研究进展%Progress in study of oral biofilm dispersal-inducing agents

    Institute of Scientific and Technical Information of China (English)

    朱彦; 杨靖梅; 段丁瑜; 徐屹

    2014-01-01

    Communities of bacteria wrapped in self-generated extracellular polymeric matrix and attached to a solid surface are known as biofilm. Biofilm formation and development can be divided into three stages: adhesion of cells to a surface, reproduction of the cells, and dispersion of cells. The procedure, which surface-attached biofilm disperses bacterial cells into the environment to colonize new sites, is defined as biofilm dispersal. Biofilm dispersal is an essential stage of biofilm life cycle. It plays an important role in the transmission of bacteria. For many pathogenic bacteria, biofilm dispersal can transform bacteria in biofilm into planktonic state and promote the spread of infection. The formation of biofilm may increase the resistance of bacteria to antimicrobial agent and host defence response compared with planktonic cells. In the oral cavity, oral microorganism can attach to the surface of oral tissue and prosthesis to form biofilm. Dental caries and periodontal disease are oral chronic infections diseases of the oral tissue. The occurrence of them has a close relationship with biofilm. The mechanism of dispersal is a hot topic in recent years. Some agents which promote dispersal might be a therapeutic potential against biofilm infections. The clinical implication of dispersal agents and potential application are promising. This article reviews the dispersal-inducing agents of oral biofilms.%生物膜是黏附在固体表面,包裹在自身产生的胞外多聚基质中的细菌群体。生物膜的形成和发展包括细菌的黏附、繁殖和分散。附着于某表面的生物膜将其中的细菌释放、分散到周围环境以传播到新的位置形成新的群落即生物膜的分散。生物膜分散是生物膜生长发展周期中一个重要的阶段,起到重要的传播作用。对许多致病菌而言,生物膜的分散能使生物膜的细菌转化为浮游状态,促进感染的扩散。生物膜的形成能提高细菌对抗

  14. Anti-tumor effect of a novel soluble recombinant human endostatin: administered as a single agent or in combination with chemotherapy agents in mouse tumor models.

    Directory of Open Access Journals (Sweden)

    Zhihua Ren

    Full Text Available Angiogenesis has become an attractive target in cancer treatment. Endostatin is one of the potent anti-angiogenesis agents. Its recombinant form expressed in the yeast system is currently under clinical trials. Endostatin suppresses tumor formation through the inhibition of blood vessel growth. It is anticipated that combined therapy using endostatin and cytotoxic compounds may exert an additive effect. In the present study, we expressed and purified recombinant human endostatin (rhEndostatin that contained 3 additional amino acid residues (arginine, glycine, and serine at the amino-terminus and 6 histidine residues in its carboxyl terminus. The recombinant protein was expressed in E. Coli and refolded into a soluble form in a large scale purification process. The protein exhibited a potent anti-tumor activity in bioassays. Furthermore, rhEndostatin showed an additive effect with chemotherapy agents including cyclophosphamide (CTX and cisplatin (DDP.rhEndostatin cDNA was cloned into PQE vector and expressed in E. Coli. The protein was refolded through dialysis with an optimized protocol. To establish tumor models, nude mice were subcutaneously injected with human cancer cells (lung carcinoma A549, hepatocellular carcinoma QGY-7703, or breast cancer Bcap37. rhEndostatin and/or DDP was administered peritumorally to evaluate the rate of growth inhibition of A549 tumors. For the tumor metastasis model, mice were injected intravenously with mouse melanoma B16 cells. One day after tumor cell injection, a single dose of rhEndostatin, or in combination with CTX, was administered intravenously or at a site close to the tumor.rhEndostatin reduced the growth of A549, QGY-7703, and Bcap37 xenograft tumors in a dose dependent manner. When it was administered peritumorally, rhEndostatin exhibited a more potent inhibitory activity. Furthermore, rhEndostatin displayed an additive effect with CTX or DDP on the inhibition of metastasis of B16 tumors or growth of

  15. Combination therapy with biologic agents in rheumatic diseases: current and future prospects

    Science.gov (United States)

    Inui, Kentaro; Koike, Tatsuya

    2016-01-01

    Strategies in rheumatoid arthritis (RA) based on ‘treat to target’ aim to control disease activity, minimize structural damage, and promote longer life. Several disease-modifying antirheumatic drugs (DMARDs) have been shown to be effective including biological DMARDs (bDMARDs). Treatment guidelines and recommendations for RA have also been published. According to those guidelines, conventional synthetic DMARDs (csDMARDs), as monotherapy or combination therapy, should be used in DMARD-naïve patients, irrespective of the addition of glucocorticoids (GCs). Combination therapies with bDMARDs are also essential for conducting treatment strategies for RA, because in every recommendation or guideline for the management of RA, combination therapies of csDMARDs with bDMARDs are recommended for RA patients with moderate or high disease activity after failure of csDMARD treatment. bDMARDs are more efficacious if used concomitantly with methotrexate (MTX) than with MTX monotherapy or bDMARD monotherapy. Thus, retention has been reported to be longer when combined with MTX. The superior efficacy of combination therapy compared with MTX monotherapy or bDMARD monotherapy could be because: (1) it could help to minimize MTX toxicity by reducing the dose of MTX, thus retention rate of the same therapeutic regimen would become high; (2) anti-bDMARD antibodies are observed at lower concentrations when using MTX concomitantly, so less clearance of bDMARDs via less formation of bDMARD and an anti-bDMARD immune complex; (3) of the additive effects of MTX to bDMARD, especially the combination of tumor necrosis factor inhibitors (TNFis) with MTX. Hence, evidence suggests that combination therapy with bDMARDs is more efficacious than monotherapy using a csDMARD or bDMARD, and that MTX is the best drug for this purpose (if MTX is not contraindicated). Finding the most effective drug regimen at the lowest cost will be the aim of RA treatment in the future. PMID:27721905

  16. Effects of combined therapy of orbital cobalt Irradiation and oral corticosteroid administration, and pulse therapy for Graves' ophthalmopathy

    Energy Technology Data Exchange (ETDEWEB)

    Shigemasa, Chiaki; Ueta, Yoshihiko; Taniguchi, Shinichi; Mitani, Yasuo; Urabe, Keita; Tanaka, Takashi; Yoshida, Akio; Mashiba, Hiroto

    1989-03-01

    This preliminary study was performed to investigate the efficacy of the combined therapy of orbital cobalt irradiation and oral prednisolone administration, and pulse therapy, for Graves' ophthalmopathy. The combined therapy was undergone according to procedure of Bartalena et al. (1983) in 5 patients. Excellent or good response to combined therapy were shown by 3 patients with short-standing ocular symptoms (3-4 months), but not by 2 patients with long-standing ocular symptoms (12-13 months). Pulse therapy was performed on 2 patients who showed no improvement from combined therapy, and on a patient who had acute onset of opthalmopathy. One gram of methylprednisolone sodium succinate was given intravenously daily for 3 successive days. This infusion procedure was repeated 3 to 4 times at intervals of 1 week. One of 2 patients who showed no improvement from combined therapy also had no response to pulse therapy. The other 2 patients showed a good response to pulse therapy and showed no relapse of ophthalmopathy for 10 and 8 months, respectively. These data emphasize the need for early immuno-suppressive therapy for Graves' ophthalmopathy. Pulse therapy may be employed in patients who show no response to other therapy method.

  17. 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

  18. Oral Xeloda plus bi-platinu two-way combined chemotherapy in treatment of advanced gastrointestinal malignancies

    Institute of Scientific and Technical Information of China (English)

    Li Fan; Wen-Chao Liu; Yan-Jun Zhang; Jun Ren; Bo-Rong Pan; Du-Hu Liu; Yan Chen; Zhao-Cai Yu

    2005-01-01

    AIM: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy.METHODS: A total of 131 patients were enrolled and randomly selected to receive either oral Xeloda (X group)or CF/5-FU (control group). Oral Xeloda 1 000 mg/m2was administered twice daily from d 1 to 14 in X group,while CF 200 mg/m2 was taken as a 2-h intravenous infusion followed by 5-FU 600 mg/m2 intravenously for 4-6 h on d 1-5 in control group. Cisplatin and oxaliplatin were administered in the same way to both the groups:cisplatin 60-80 mg/m2 by hyperthermic intraperitoneal administration, and oxaliplatin 130 mg/m2 intravenously for 2 h on d 1. All the drugs were recycled every 21 d,with at least two cycles. Pyridoxine 50 mg was given t.i.d.orally for prophylaxis of the hand-foot syndrome (HFS).Then the effect, adverse events, cost-effectiveness and DI of the two groups were evaluated.RESULTS: Hundred and fourteen cases (87.0%) finished more than two chemotherapy cycles. The overall response rate of them was 52.5% (X group) and 42.4% (control group) respectively. Tumor progression time (TTP) was 7.35 mo vs5.95 mo, and 1-year survival rate was 53.1% vs 44.5%. There was a remarkable statistical significance of TTP and 1-year survival between the two groups. The main Xeloda-related adverse events were myelosuppression,gastrointestinal toxicity, neurotoxicity and HFS, which were mild and well tolerable. Therefore, no patients withdrew from the study due to side effects before two chemotherapy cycles were finished. Both groups finished pre-arranged DI and the relative DI was nearly 1.0. The average cost for 1 patient in one cycle was $9 137.35(X group) and $8 961.72 (control group), or US $1 100.89in X group and $1 079.73 in control group. To add 1% to the response rate costs $ 161.44 vs $210

  19. Effects of Atomoxetine and Osmotic Release Oral System-Methylphenidate on Executive Functions in Patients with Combined Type Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Ince Tasdelen, Bedia; Karakaya, Emel; Oztop, Didem Behice

    2015-08-01

    The aim of this study was to evaluate and compare the effects of atomoxetine (ATX) and osmotic release oral system-methylphenidate (OROS-MPH) therapies on executive functions, activities, treatment response time, and adverse effects based on discernible clinical effects in children with combined type attention-deficit/hyperactivity disorder (ADHD). The study sample consisted of 43 children 7-12 years of age, who presented to the outpatient clinic with inattention, hyperactivity, and impulsivity for the first time, and were diagnosed as having combined type ADHD according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria but had not previously used any medication for ADHD. The Wisconsin Card Sorting Test (WCST), Stroop Test TBAG Form (STP), and Visual Auditory Digit Span B (VADS B) were applied to all the patients included. Neuropsychological tests were repeated in 33 patients with good clinical recovery based on the Clinical Global Impressions-Improvement (CGI-I) scale (CGI-I ≤2) at the week in which clinical recovery was observed. The time limit for treatment response was set as 20 weeks. It was found that there was significantly increased performance in executive functions with ATX and OROS-MPH in both groups. It was seen that although significantly increased performance was achieved in both perseveration and conceptual learning and reasoning domains by both agents, there was increased performance in more domains by the OROS-MPH group in WSCT. Mean doses were 1.31±0.37 mg/kg/day in the ATX group and 0.90±0.29 mg/kg/day in the OROS-MPH group. Comparable effectiveness (76.19% for ATX vs. 77.27% for OROS-MPH) and adverse effects (57.14% for ATX vs. 54.54% for OROS-MPH) were detected in both groups, whereas there was a significant difference in clinical response times between the groups (13 weeks for ATX vs. 7 weeks for OROS-MPH, p <0.001). At the end of the study, it was seen that clinical recovery achieved by ATX and OROS

  20. Bimodal Imaging Probes for Combined PET and OI: Recent Developments and Future Directions for Hybrid Agent Development

    Directory of Open Access Journals (Sweden)

    Uwe Seibold

    2014-01-01

    Full Text Available Molecular imaging—and especially positron emission tomography (PET—has gained increasing importance for diagnosis of various diseases and thus experiences an increasing dissemination. Therefore, there is also a growing demand for highly affine PET tracers specifically accumulating and visualizing target structures in the human body. Beyond the development of agents suitable for PET alone, recent tendencies aim at the synthesis of bimodal imaging probes applicable in PET as well as optical imaging (OI, as this combination of modalities can provide clinical advantages. PET, due to the high tissue penetration of the γ-radiation emitted by PET nuclides, allows a quantitative imaging able to identify and visualize tumors and metastases in the whole body. OI on the contrary visualizes photons exhibiting only a limited tissue penetration but enables the identification of tumor margins and infected lymph nodes during surgery without bearing a radiation burden for the surgeon. Thus, there is an emerging interest in bimodal agents for PET and OI in order to exploit the potential of both imaging techniques for the imaging and treatment of tumor diseases. This short review summarizes the available hybrid probes developed for dual PET and OI and discusses future directions for hybrid agent development.

  1. Analysis of Oral Hypoglycemic Agents Used in Our Hospital during 2008-2010%我院2008-2010年口服降糖药的用药分析

    Institute of Scientific and Technical Information of China (English)

    朱寅

    2011-01-01

    目的 了解医院口服降糖药的使用情况,促进合理用药.方法 对重庆医科大学附属第二医院2008年至2010年口服降糖药的应用频率、消耗金额进行统计分析.结果 该院口服降糖药的消耗金额逐年增长,其中二甲双胍增幅较大;临床最常用的口服降糖药是二甲双胍、阿卡波糖和格列吡嗪.结论 医院口服降糖药的使用呈增长趋势.%Objective To evaluate the application status of oral hypoglycemic agents used in the hospital for promoting rational drug use.Methods The frequency and sum of money in consumption of oral hypoglycemic agents during 2008 - 2010 were statistically analyzed.Results The sum of money in consumption of oral hypoglycemic agents in the hospital was increased year by year, in which, the increment of metformin was maximum. The commonest used oral hypoglycemic agents in clinic were metformin, glipizide and pioglipazong. Conclusion The use of oral hypoglycemic agents presents the increasing trend.

  2. Effects of combination therapy with direct hemoperfusion using polymyxin B-immobilized fiber and oral vancomycin on fulminant pseudomembranous colitis with septic shock.

    Science.gov (United States)

    Kimura, Yoshihide; Sato, Koichi; Tokuda, Hiroshi; Nakamura, Naka; Dohi, Yasuaki; Orito, Etsuro; Mizokami, Masashi

    2007-03-01

    We report 2 cases of fulminant pseudomembranous colitis with septic shock. The first case showed few symptoms, whereas the second case showed recurrence. Both cases rapidly developed shock and blood pressure was uncontrollable except with the use of pressor agents. Direct hemoperfusion using polymyxin B-immobilized fiber, which was previously demonstrated to have excellent therapeutic effects for the treatment of hypotension in septic shock by removing circulating lipopolysaccharide and oral vancomycin dramatically improved both cases' clinical status and decreased their APACHE II scores (from 18 to 8 and from 16 to 9 points, respectively). Therefore, we suggest that direct hemoperfusion using polymyxin B-immobilized fiber improved hypotension-correcting cytokine balance with adsorption of endogenous cannabinoids in serum. Although colectomy is often performed to treat fulminant pseudomembranous colitis with septic shock, direct hemoperfusion can be easily performed with little risk to the patient. These cases strongly indicated that our combination therapy provides an important treatment for fulminant pseudomembranous colitis with septic shock.

  3. The efficacy and plasma profiles of abamectin plus levamisole combination anthelmintics administered as oral and pour-on formulations to cattle.

    Science.gov (United States)

    Leathwick, D M; Miller, C M; Sauermann, C W; Candy, P M; Ganesh, S; Fraser, K; Waghorn, T S

    2016-08-30

    In phase I, faecal egg count reduction tests (FECRT) were conducted on six commercial cattle farms to compare the performance of two pour-on and one oral combination anthelmintic. Groups of 12-15 calves were sampled for faecal nematode egg count (FEC) before treatment with either abamectin oral, levamisole oral, an abamectin+levamisole oral combination or one of two abamectin+levamisole combination pour-ons. Samples were collected again 14days after treatment to calculate the percentage reduction in FEC. The proportions of infective stage larvae (L3) in faecal cultures were used to apportion egg counts to, and calculate efficacy against, the main parasite genera. Abamectin oral was effective against Ostertagia except on one farm where resistance was indicated, but had reduced efficacy against Cooperia on four farms. Levamisole oral was effective against Cooperia on all farms, but had variable efficacy against Ostertagia. The abamectin+levamisole oral was effective against both species on all farms. The abamectin+levamisole pour-ons were effective on some farms but not on others. In particular, pour-on 2 failed to achieve 95% efficacy in 45% of evaluations, 4/6 against Cooperia and 1/5 against Ostertagia. On some farms the combination pour-ons were less effective than their constituent actives administered alone as orals. In phase II, 8 groups of 6 calves, grazing parasite-free pasture, were infected with putatively ML-resistant isolates of Cooperia oncophora and Ostertagia ostertagi. Once infections were patent groups were treated with oral or pour-on formulations of abamectin alone, levamisole alone, abamectin+levamisole (two pour-ons) or remained untreated. Blood samples were collected for analysis and after 8days all calves were euthanized and abomasa and intestines recovered for worm counts. All treatments were effective against O. ostertagi and all treatments containing levamisole were effective against C. oncophora. Animals treated with the oral combination

  4. Experimental and Clinical Evaluation of Plantago australis Extract as an Anti-Inflammatory Agent to Treat Oral Pathologies

    Directory of Open Access Journals (Sweden)

    Flores

    2016-09-01

    Full Text Available Background Plantago australis is a native plant from Southern Brazil used to reduce inflammation. Interestingly, there are no previous studies evaluating its use to treat oral lesions. Objectives The study aimed to investigate in vivo the anti-inflammatory activity of 10% ethanol extract of P. australis in recurrent aphthous stomatitis (RAS, erosive lichen planus (ELP and actinic cheilitis (AC. Methods Thirty patients with RAS, ELP and AC were treated topically with 10% P. australis solution-based or cream. Results In the comparison of in vivo data before and after the treatment and between different lesions, all P values were less than 0.05. Conclusions The pharmaceutical formulation of 10% P. australis was therapeutically effective in the subjects with inflammatory oral lesions of RAS, ELP and AC.

  5. Canagliflozin: Efficacy and Safety in Combination with Metformin Alone or with Other Antihyperglycemic Agents in Type 2 Diabetes.

    Science.gov (United States)

    Qiu, Rong; Balis, Dainius; Capuano, George; Xie, John; Meininger, Gary

    2016-12-01

    Metformin is typically the first pharmacologic treatment recommended for type 2 diabetes mellitus (T2DM), but many patients do not achieve glycemic control with metformin alone and eventually require combination therapy with other agents. Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was assessed in a comprehensive Phase 3 clinical development program consisting of ~10,000 participants, of which ~80% were on background therapy that consisted of metformin alone or in combination with other antihyperglycemic agents (AHAs; e.g., pioglitazone, sulfonylurea, and insulin). In addition, the efficacy and safety of canagliflozin and metformin as the initial combination therapy and canagliflozin monotherapy were assessed versus metformin in treatment-naïve patients with T2DM. Across studies in patients with T2DM who were on metformin alone or in combination with other AHAs, canagliflozin 100 and 300 mg provided improvements in glycated hemoglobin for up to 104 weeks. Canagliflozin was also associated with reductions in body weight and systolic blood pressure when added to background therapy consisting of metformin alone or with other AHAs. Canagliflozin was generally well tolerated, with increased incidence of adverse events (AEs) related to the mechanism of SGLT2 inhibition (i.e., genital mycotic infections, urinary tract infections, and osmotic diuresis-related AEs). Consistent with its insulin-independent mechanism of action, canagliflozin was associated with low rates of hypoglycemia when background therapy did not include sulfonylurea or insulin. Due to its favorable efficacy and safety profile, these results suggest that adding canagliflozin to a background regimen consisting of metformin or implementing treatment with a fixed-dose regimen of canagliflozin and metformin would provide an effective and safe treatment regimen for T2DM management.

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

    Science.gov (United States)

    Villarrubia, Gabriel; Paz, Juan F De; Iglesia, Daniel H De La; Bajo, Javier

    2017-08-02

    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.

  7. 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.

  8. Percutaneous exposure to the nerve agent VX: Efficacy of combined atropine, obidoxime and diazepam treatment.

    Science.gov (United States)

    Joosen, Marloes J A; van der Schans, Marcel J; van Helden, Herman P M

    2010-10-06

    The nerve agent VX is most likely to enter the body via liquid contamination of the skin. After percutaneous exposure, the slow uptake into the blood, and its slow elimination result in toxic levels in plasma for a period of several hours. Consequently, this has implications for the development of toxic signs and for treatment onset. In the present study, clinical signs, toxicokinetics and effects on respiration, electroencephalogram and heart rate were investigated in hairless guinea pigs after percutaneous exposure to 500 microg/kg VX. We found that full inhibition of AChE and partial inhibition of BuChE in blood were accompanied by the onset of clinical signs, reflected by a decline in respiratory minute volume, bronchoconstriction and a decrease in heart rate. Furthermore, we investigated the therapeutic efficacy of a single dose of atropine, obidoxime and diazepam, administered at appearance of first clinical signs, versus that of repetitive dosing of these drugs on the reappearance of signs. A single shot treatment extended the period to detrimental physiological decline and death for several hours, whereas repetitive administration remained effective as long as treatment was continued. In conclusion, percutaneous VX poisoning showed to be effectively treatable when diagnosed on time and when continued over the entire period of time during which VX, in case of ineffective decontamination, penetrates the skin.

  9. [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.

  10. An oral recombinant vaccine in dogs against Echinococcus granulosus, the causative agent of human hydatid disease: a pilot study.

    Directory of Open Access Journals (Sweden)

    Anne-Francoise Petavy

    Full Text Available Dogs are the main source of human cystic echinococcosis. An oral vaccine would be an important contribution to control programs in endemic countries. We conducted two parallel experimental trials in Morocco and Tunisia of a new oral vaccine candidate against Echinococcus granulosus in 28 dogs. The vaccine was prepared using two recombinant proteins from adult worms, a tropomyosin (EgTrp and a fibrillar protein similar to paramyosin (EgA31, cloned and expressed in a live attenuated strain of Salmonella enterica serovar typhimurium.In each country, five dogs were vaccinated with the associated EgA31 and EgTrp; three dogs received only the vector Salmonella; and six dogs were used as different controls. The vaccinated dogs received two oral doses of the vaccine 21 d apart, and were challenged 20 d later with 75,000 living protoscoleces. The controls were challenged under the same conditions. All dogs were sacrificed 26-29 d postchallenge, before the appearance of eggs, for safety reasons.We studied the histological responses to both the vaccine and control at the level of the duodenum, the natural localization of the cestode. Here we show a significant decrease of parasite burden in vaccinated dogs (70% to 80% and a slower development rate in all remaining worms. The Salmonella vaccine EgA31-EgTrp demonstrated a high efficacy against E. granulosus promoting its potential role in reducing transmission to humans and animals.

  11. In vitro interaction of certain antimicrobial agents in combination with plant extracts against some pathogenic bacterial strains

    Institute of Scientific and Technical Information of China (English)

    Kalpna Rakholiya; Sumitra Chanda

    2012-01-01

    Objective: To evaluate the in vitro interaction between methanolic extracts of Terminalia catappa (Combretaceae) (T. catappa) and Carica papaya (caricaceae) (C. papaya) leaves and certain known antimicrobial drugs like penicillin G (P), ampicillin (AMP), amoxyclav (AMC), cephalothin (CEP), polymyxin B (PB), rifampicin (RIF), amikacin (AK), nilidixic acid (NA), gentamicin (GEN), chloramphenicol (C), ofloxacin (OF) against five Gram positive and five Gram negative bacteria.Methods:Evaluation of synergy interaction between plant extracts and antimicrobial agents was carried out using disc diffusion method. Results: The results of this study showed that there is an increased activity in case of combination of methanolic plant extracts and test antimicrobial agents. The more potent result was that the synergism between methanolic extract of C. papaya and antibiotics showed highest and strong synergistic effect against tested bacterial strains;though methanolic extract of C. papaya alone was not showing any antibacterial activity.Conclusions:These results indicate that combination between plant extract and the antibiotics could be useful in fighting emerging drug-resistance microorganisms.

  12. In vitro interaction of certain antimicrobial agents in combination with plant extracts against some pathogenic bacterial strains

    Institute of Scientific and Technical Information of China (English)

    Kalpna Rakholiya; Sumitra Chanda

    2012-01-01

    Objective: To evaluate the in vitro interaction between methanolic extracts of Terminalia catappa (T. catappa) (Combretaceae) and Carica papaya (C. papaya) (caricaceae) leaves and certain known antimicrobial drugs like penicillin G (P), ampicillin (AMP), amoxyclav (AMC), cephalothin (CEP), polymyxin B (PB), rifampicin (RIF), amikacin (AK), nilidixic acid (NA), gentamicin (GEN), chloramphenicol (C), ofloxacin (OF) against five Gram positive and five Gram negative bacteria. Methods: Evaluation of synergy interaction between plant extracts and antimicrobial agents was carried out using disc diffusion method. Results: The results of this study showed that there is an increased activity in case of combination of methanolic plant extracts and test antimicrobial agents. The more potent result was that the synergism between methanolic extract of C. papaya and antibiotics showed highest and strong synergistic effect against tested bacterial strains;though methanolic extract of C. papaya alone was not showing any antibacterial activity. Conclusions: These results indicate that combination between plant extract and the antibiotics could be useful in fighting emerging drug-resistance microorganisms.

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

    Directory of Open Access Journals (Sweden)

    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.

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

    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. PMID:26422151

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Increased apparent oral clearance of valproic acid during intake of combined contraceptive steroids in women with epilepsy.

    Science.gov (United States)

    Galimberti, Carlo Andrea; Mazzucchelli, Iolanda; Arbasino, Carla; Canevini, Maria Paola; Fattore, Cinzia; Perucca, Emilio

    2006-09-01

    To determine potential changes in total and unbound serum valproic acid (VPA) concentrations at steady-state during a cycle of intake of combined hormonal contraceptive (HC) steroids. Blood samples were collected from nine women stabilized on VPA monotherapy on two separate randomized occasions: (i) at the end of the 4- to 7-day HC-free interval, and (ii) on the last day of the HC intake period. Trough concentrations of VPA in serum and serum ultrafiltrates were determined by fluorescence polarization immunoassay. In all women, total and unbound VPA concentrations were higher during the HC-free interval than during HC intake (means +/- SD: 425 +/- 184 vs. 350 +/- 145 micromol/L, respectively, for total VPA, p = 0.002, and 55 +/- 37 vs. 39 +/- 25 micromol/L, respectively, for unbound VPA, p = 0.005). Compared with the HC-free interval, HC intake was associated with a mean 21.5% increase in VPA total apparent oral clearance (from 8.0 +/- 5.2 to 9.7 +/- 6.4 ml/h/kg, p = 0.01) and a 45.2 % increase in VPA unbound apparent oral clearance (from 79 +/- 81 to 115 +/- 121 ml/h/kg, p = 0.029). The apparent oral clearance of total and unbound VPA increases during the HC intake period compared with the HC-free interval, probably due to induction of glucuronosyltransferase by ethinylestradiol. The magnitude of the change varies across individuals, being potentially clinically relevant in some cases. Serum VPA concentrations should be monitored when adding or discontinuing HC steroids, and possibly during the on-off intervals of a HC cycle.

  20. Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans: an observational cohort study.

    Science.gov (United States)

    O'Brien, Daniel P; McDonald, Anthony; Callan, Peter; Robson, Mike; Friedman, N Deborah; Hughes, Andrew; Holten, Ian; Walton, Aaron; Athan, Eugene

    2012-01-01

    Mycobacterium ulcerans infections, and fluoroquinolone combined with rifampicin-containing antibiotic regimens can provide an effective and safe oral treatment option.

  1. Successful Outcomes with Oral Fluoroquinolones Combined with Rifampicin in the Treatment of Mycobacterium ulcerans: An Observational Cohort Study

    Science.gov (United States)

    O'Brien, Daniel P.; McDonald, Anthony; Callan, Peter; Robson, Mike; Friedman, N. Deborah; Hughes, Andrew; Holten, Ian; Walton, Aaron; Athan, Eugene

    2012-01-01

    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. PMID:22272368

  2. Combined therapy of Salmonella infection in chickens by antimicrobial agents followed by cultured cecal bacteria.

    Science.gov (United States)

    Seuna, E; Schneitz, C; Nurmi, E

    1980-06-01

    Week-old chickens infected with Salmonella infantis when one day old were treated with antimicrobial drugs either given alone or followed by peroral inoculation of bacterial culture. The bacteria were derived from the cecal contents of adult chickens. The antimicrobial drugs used were: neomycin, neomycin plus oxytetracycline, neomycin plus polymyxin, and sulfadiazine plus trimethoprim. The combined therapy with oxytetracycline plus neomycin and bacterial culture seemed to be the most effective, although the efficacy varied between the parallel trials. Sulfadiazine plus trimethoprim followed by treatment with the bacterial culture decreased the infection rate. The bacterial culture alone also had a slight anti-salmonella effect. When only antimicrobials were given, salmonellae rapidly reappeared in the intestines when the therapy was stopped.

  3. Phase I trial evaluating the antiviral agent Cidofovir in combination with chemoradiation in cervical cancer patients

    Science.gov (United States)

    Deutsch, Eric; Haie-Meder, Christine; Bayar, Mohamed Amine; Mondini, Michele; Laporte, Mélanie; Mazeron, Renaud; Adam, Julien; Varga, Andrea; Vassal, Gilles; Magné, Nicolas; Chargari, Cyrus; Lanoy, Emilie; Pautier, Patricia; Levy, Antonin; Soria, Jean-Charles

    2016-01-01

    Purpose This phase I trial aimed to assess the safety and determine the recommended Phase II dose (RP2D) of Cidofovir combined with chemoradiotherapy in patients with stage IB2-IVA cervical cancer. Experimental design Incremental doses (1, 2.5, 5 and 6.5 mg/kg) of IV Cidofovir were administered weekly for two weeks, and then every 2 weeks from the start of chemoradiotherapy to the initiation of utero-vaginal brachytherapy. Biological expression of HPV was analyzed during treatment and tumor response was assessed according to RECIST v1.0 criteria. Results A total of 15 patients were treated with Cidofovir. Dose-limiting toxicities occurred in 2/6 patients at the 6.5 mg/kg dose level (G3 proteinuria, and G3 acute pyelonephritis with G3 febrile neutropenia). No toxicity occurred at the 5 mg/kg dose level, but only 3 patients received this dose due to trial interruption because of low accrual. The most frequent G3-4 adverse effects observed during the trial were: abdominal pain (n=3), infection (n=2), leuckoneutropenia (n=2), and others (n=6). No toxic death or major renal side effect occurred. The best response was that 8/9 evaluable patients achieved a complete response (89%). In the intention to treat population, the 2-year overall and progression-free survival rates were 93% and 76%, respectively. Biological monitoring of HPV-related markers (decreased p16 expression, and increased p53 and pRb levels) was possible on sequential tumor biopsy samples. The genomic alterations identified were PIK3CA (n=5; one also had a KRAS mutation), and HRAS (n=1) mutations. Conclusion Cidofovir at a dose of 5mg/kg combined with chemoradiotherapy appeared tolerable and yielded tumor regressions. Due to early trial interruption, the RP2D was not confirmed. PMID:27016411

  4. Simultaneous reconstruction of the oral commissure, lip and buccal mucosa with microvascular transfer of combined first-second toe web and dorsalis pedis flap.

    Science.gov (United States)

    Ciudad, Pedro; Maruccia, Michele; Sapountzis, Stamatis; Chen, Hung-Chi

    2016-10-01

    The reconstruction of oral commissure, lip and mucosa defects following tumour resection is a challenging task to the reconstructive surgeon owing to the increasing aesthetic and functional demands. The authors describe a case in which the use of combined first-second toe web with dorsalis pedis flap was transferred and an optimal result was achieved for the oral commissure, lip and buccal mucosa following resection of squamous cell carcinoma and local flap failure.

  5. Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents.

    Science.gov (United States)

    Tsatsos, Michael; MacGregor, Cheryl; Athanasiadis, Ioannis; Moschos, Marilita M; Hossain, Parwez; Anderson, David

    2016-12-01

    Ophthalmic herpes simplex viral keratitis is responsible for a range of ocular manifestations from superficial epithelial disease to stromal keratitis and endotheliitis. The Herpetic Eye Disease Study has guided the management of herpetic eye disease for almost twenty years, but newer medications such as valacyclovir are now available and are considered to have better bioavailability than acyclovir. In this review, we examine the existing evidence on the pathogenesis of different ophthalmic herpes simplex viral keratitis disease modalities and the role of oral and topically administered antiviral drugs in the treatment of herpes simplex viral keratitis.

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

    Institute of Scientific and Technical Information of China (English)

    Pei Shi

    2006-01-01

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

  7. 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.

  8. Combined immersion and oral vaccination of Vietnamese catfish (Pangasianodon hypophthalmus) confers protection against mortality caused by Edwardsiella ictaluri.

    Science.gov (United States)

    Thinh, N H; Kuo, T Y; Hung, L T; Loc, T H; Chen, S C; Evensen, O; Schuurman, H J

    2009-12-01

    Edwardsiella ictaluri septicemia occurs worldwide and causes high mortality and considerable economic damage to the catfish industry especially in Vietnam and the USA. To control Edwardsiella septicemia farmers extensively use antibiotics and various vaccination methods. Vaccination with inactivated vaccines has come with variable efficacy. In this trial the results of an approach of controlling Edwardsiella septicemia of Tra catfish (Pangasianodon hypophthalmus) in Vietnam through vaccination via mucosal surfaces are presented. The results show that a combination of primary vaccination by immersion with inactivated E. ictaluri followed by an oral boost with a formulated antigen preparation induces a statistically significant level of protection against mortality caused by experimental infection 4 weeks post-boost. Fish immunized by immersion only show significantly lower level of protection but significantly higher than the controls. Repeated boosts result in improved duration of immunity with a relative percent survival (RPS) of 47% at 90% control mortality. The immunization procedure provides an alternative for disease control through vaccination.

  9. Treatment with a combination of intra-oral sensory stimulation and electropalatography in a child with severe developmental dyspraxia.

    Science.gov (United States)

    Lundeborg, Inger; McAllister, Anita

    2007-01-01

    This paper describes the use of a combination of intra-oral sensory stimulation and electropalatography (EPG) in the treatment of a case with severe developmental verbal dyspraxia. A multiple-baseline design was used. The treatment duration was 11 months and started when the subject was 5 years old. The efficacy of the treatment was assessed by calculations of percentage of correctly articulated words, percentage of consonants correct, percentage of phonemes correct and percentage of words correct. Intelligibility assessments were conducted by both naïve and expert listeners. The experts also assessed visual deviances in articulatory gestures from video recordings. Qualitative analysis of EPG data was made. The subject's speech was significantly improved by the treatment in all aspects. The results and their generalization to other cases of developmental verbal dyspraxia are discussed.

  10. Combined perfusion and doppler imaging using plane-wave nonlinear detection and microbubble contrast agents.

    Science.gov (United States)

    Tremblay-Darveau, Charles; Williams, Ross; Milot, Laurent; Bruce, Matthew; Burns, Peter N

    2014-12-01

    Plane-wave imaging offers image acquisition rates at the pulse repetition frequency, effectively increasing the imaging frame rates by up to two orders of magnitude over conventional line-by-line imaging. This form of acquisition can be used to achieve very long ensemble lengths in nonlinear modes such as pulse inversion Doppler, which enables new imaging trade-offs that were previously unattainable. We first demonstrate in this paper that the coherence of microbubble signals under repeated exposure to acoustic pulses of low mechanical index can be as high as 204 ± 5 pulses, which is long enough to allow an accurate power Doppler measurement. We then show that external factors, such as tissue acceleration, restrict the detection of perfusion at the capillary level with linear Doppler, even if long Doppler ensembles are considered. Hence, perfusion at the capillary level can only be detected with ultrasound through combined microbubbles and Doppler imaging. Finally, plane-wave contrast-enhanced power and color Doppler are performed on a rabbit kidney in vivo as a proof of principle. We establish that long pulse-inversion Doppler sequences and conventional wall-filters can create an image that simultaneously resolves both the vascular morphology of veins and arteries, and perfusion at the capillary level with frame rates above 100 Hz.

  11. The neurobiology of bipolar disorder: identifying targets for specific agents and synergies for combination treatment.

    Science.gov (United States)

    Andreazza, Ana C; Young, L Trevor

    2014-07-01

    Bipolar disorder (BD) is a chronic psychiatric illness described by severe changes in mood. Extensive research has been carried out to understand the aetiology and pathophysiology of BD. Several hypotheses have been postulated, including alteration in genetic factors, protein expression, calcium signalling, neuropathological alteration, mitochondrial dysfunction and oxidative stress in BD. In the following paper, we will attempt to integrate these data in a manner which is to understand targets of treatment and how they may be, in particular, relevant to combination treatment. In summary, the data suggested that BD might be associated with neuronal and glial cellular impairment in specific brain areas, including the prefrontal cortex. From molecular and genetics: (1) alterations in dopaminergic system, through catechol-O-aminotransferase; (2) decreased expression and polymorphism on brain-derived neurotrophic factor; (3) alterations cyclic-AMP responsive element binding; (4) dysregulation of calcium signalling, including genome-wide finding for voltage-dependent calcium channel α-1 subunit are relevant findings in BD. Future studies are now necessary to understand how these molecular pathways interact and their connection to the complex clinical manifestations observed in BD.

  12. Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy.

    Science.gov (United States)

    Viscomi, Carlo; Burlina, Alberto B; Dweikat, Imad; Savoiardo, Mario; Lamperti, Costanza; Hildebrandt, Tatjana; Tiranti, Valeria; Zeviani, Massimo

    2010-08-01

    Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantially prolonged the lifespan of Ethe1-deficient mice, with the combined treatment being additive. The same dual treatment caused marked clinical improvement in five affected children, with hardly any adverse or side effects.

  13. Transcriptional changes in the brains of cattle orally infected with the bovine spongiform encephalopathy agent precede detection of infectivity.

    Science.gov (United States)

    Tang, Yue; Xiang, Wei; Hawkins, Steve A C; Kretzschmar, Hans A; Windl, Otto

    2009-09-01

    Bovine spongiform encephalopathy (BSE) is a fatal, transmissible, neurodegenerative disease of cattle. BSE can be transmitted experimentally between cattle through the oral route, and in this study, brain tissue samples from animals at different time points postinoculation were analyzed for changes in gene expression. The aims of this study were to identify differentially regulated genes during the progression of BSE using microarray-based gene expression profiling and to understand the effect of prion pathogenesis on gene expression. A total of 114 genes were found to be differentially regulated over the time course of the infection, and many of these 114 genes encode proteins involved in immune response, apoptosis, cell adhesion, stress response, and transcription. This study also revealed a broad correlation between gene expression profiles and the progression of BSE in cattle. At 21 months postinoculation, the largest number of differentially regulated genes was detected, suggesting that there are many pathogenic processes in the animal brain even prior to the detection of infectivity in the central nervous systems of these orally infected cattle. Moreover, evidence is presented to suggest that it is possible to predict the infectious status of animals using the expression profiles from this study.

  14. Oral combined therapy with probiotics and alloantigen induces B cell-dependent long-lasting specific tolerance.

    Science.gov (United States)

    Mercadante, Ana C T; Perobelli, Suelen M; Alves, Ana P G; Gonçalves-Silva, Triciana; Mello, Wallace; Gomes-Santos, Ana C; Miyoshi, Anderson; Azevedo, Vasco; Faria, Ana M C; Bonomo, Adriana

    2014-02-15

    Allogeneic hematopietic stem cell transplantation (aHSCT) is widely used for the treatment of hematologic malignancies. Although aHSCT provides a good response against the malignant cells (graft-versus-leukemia [GVL]), it also leads to the development of graft-versus-host disease (GVHD), a severe disease with high mortality and morbidity rates. Therapy for GVHD is commonly based on nonspecific immunosupression of the transplanted recipient, resulting in the concomitant inhibition of the GVL effect. In this study, we propose an alternative approach to specifically suppress GVHD while sparing the GVL, based on oral treatment of transplant donors with recipient Ags, associated with the intake of probiotic Lactococcus lactis as tolerogenic adjuvant (combined therapy). We show that treatment of C57BL/6 donor mice with combined therapy before the transplant protects the recipients F1 (C57BL/6 × BAL/c) mice from clinical and pathological manifestations of disease, resulting in 100% survival rate. Importantly, the animals keep the immunological competence maintaining the GVL response as well as the response to third-party Ags. The protection is specific, long lasting and dependent on donor IL-10-sufficient B cells activity, which induces regulatory T cells in the host. These data suggest that combined therapy is a promising strategy for prevention of GVHD with preservation of GVL, opening new possibilities to treat human patients subjected to transplantation.

  15. The intravenous and oral pharmacokinetics of afoxolaner and milbemycin oxime when used as a combination chewable parasiticide for dogs.

    Science.gov (United States)

    Letendre, L; Harriman, J; Drag, M; Mullins, A; Malinski, T; Rehbein, S

    2017-01-01

    The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated following the oral administration of NexGard Spectra(®) (Merial), a fixed combination chewable formulation of these two active pharmaceutical ingredients. Absorption of actives was rapid at levels that provide the minimum effective doses of 2.5 mg/kg and 0.5 mg/kg of afoxolaner and milbemycin oxime, respectively. The time to maximum afoxolaner plasma concentrations (tmax ) was 2-4 h. The milbemycin tmax was 1-2 h. The terminal plasma half-life (t1/2 ) and the oral bioavailability were 14 ± 3 days and 88.3% for afoxolaner, 1.6 ± 0.4 days and 80.5% for milbemycin oxime A3 and 3.3 ± 1.4 days and 65.1% for milbemycin oxime A4. The volume of distribution (Vd ) and systemic clearance (Cls) were determined following an IV dose of afoxolaner or milbemycin oxime. The Vd was 2.6 ± 0.6, 2.7 ± 0.4 and 2.6 ± 0.6 L/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The Cls was 5.0 ± 1.2, 75 ± 22 and 41 ± 12 mL/h/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The pharmacokinetic profile for the combination of afoxolaner and milbemycin oxime supports the rapid onset and a sustained efficacy for afoxolaner against ectoparasites and the known endoparasitic activity of milbemycin oxime.

  16. Combined Effect of Some Bio-Agents on the Grasshopper, Hetiracris littoralis Under Semi-Field Condition

    Directory of Open Access Journals (Sweden)

    Aziza Sharaby

    2013-06-01

    Full Text Available LC50 of the alchoholic-80% extract of Euphorbia pulchrrima (0.714%, essential oil of Garlic plant Allium sativum (0.067% and nematodes of Steinernima sp. and Heterorhabditis sp. (500 IJs/ml, were tested for their solely and/or combined toxic effects and for their effects on some biological aspects against the grasshopper, Heteracris littoralis 1st instar nymphs under semi-field condition. The joint action of the mixture of the most effective extract (E. pulchrrima and oil (Garlic oil exhibit an antagonistic effect with co-toxicity index of (–24, despite the increase the proportion of death in the mixture for all the tested groups the type of interaction were antagonism, all the tested materials had variable mode of action which resulted in significantly antagonistic effects. Euphorbia 80% methanol extract and Garlic oil may use separately or in combination as alternatives safe tools against H. littoralis grasshopper. Semi-field experiments cleared that nematodes in combination with the oil or extract increased the mortality percentage. The combination mixture of extract, oil and nematode significantly affected development, reproduction and life cycle of H. littoralis. Lethal effect varied with regard to the nematode species. Semi-field experiment of the plant extract, plant oil and their mixture revealed some changes on the biological aspects, an increase in the nymphal period, pre-oviposition, oviposition and post-oviposition periods. There is vigorous decrease in the female fecundity and fertility. The control of the insect by nematode and sub-lethal dose of plant extract or plant volatile oil as biological control may enhance their lethal effect on insect pest when applied simultaneously. Combination mixture of the tested bio-agent could be considered as possible means for use in programs of integrated pest management of H. littoralis grasshopper.

  17. Thrice-daily biphasic insulin aspart 30 may be another therapeutic option for Chinese patients with type 2 diabetes inadequately controlled with oral antidiabetic agents

    Institute of Scientific and Technical Information of China (English)

    YANG Wen-ying; JI Qiu-he; ZHU Da-long; YANG Jin-kui; CHEN Lu-lu; LIU Zhi-min; YU De-min; YAN Li

    2009-01-01

    In subjects with type 2 diabetes inadequately controlled with oral antidiabetic agents (OADs), insulin therapy is usually started to improve glycaemic control after failure of diet, exercise and OADs.1 Although there is no standard way to introduce insulin treatment, premixed formulations are a popular option. They offer an alternative to basal-bolus therapy and provide basal and prandial coverage with a single injection. Indeed, Koivisto et al2 in 1999 reported that 39% of patients with type 2 diabetes worldwide used premixed insulin as part of their therapeutic regimen. The modem premixed insulins, such as biphasic insulin aspart 30 (BIAsp 30) are most frequently prescribed twice-daily (BID) in clinical Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, China (Yang WY)

  18. Therapeutic drug monitoring for either oral or intravenous busulfan when combined with pre- and post-transplantation cyclophosphamide.

    Science.gov (United States)

    Lombardi, Lindsey R; Kanakry, Christopher G; Zahurak, Marianna; Durakovic, Nadira; Bolaños-Meade, Javier; Kasamon, Yvette L; Gladstone, Douglas E; Matsui, William; Borrello, Ivan; Huff, Carol Ann; Swinnen, Lode J; Brodsky, Robert A; Ambinder, Richard F; Fuchs, Ephraim J; Rosner, Gary L; Jones, Richard J; Luznik, Leo

    2016-01-01

    Busulfan (Bu)/cyclophosphamide (Cy) is a standard conditioning platform for allogeneic transplantation. We developed a strategy separating the Cy into two pre/post-transplantation doses (PTCy), providing myeloablative conditioning and single-agent graft-versus-host disease (GVHD) prophylaxis. We investigated the impact of Bu route on treatment-related toxicity for 131 consecutive adult patients. Busulfan was administered in four daily divided doses either orally (n = 72) or intravenously (n = 59) with pharmacokinetics on the first-dose and as necessary on subsequent doses to achieve a target area-under-the-concentration-curve (AUC) of 800-1400 μmol*min/L per dose. BuCy/PTCy with pharmacokinetics is well-tolerated with low treatment-related toxicity. Hepatic veno-occlusive disease incidence was 6% with two fatal events. Bu administration route in the context of BuCy/PTCy did not statistically impact hepatotoxicity, GVHD, relapse, disease-free survival, or overall survival. The BuCy/PTCy platform has a low incidence of treatment-related toxicity, including hepatotoxicity, in hematologic malignancies when using pharmacokinetics for a target AUC of 800-1400 μmol*min/L, irrespective of Bu administration route.

  19. Prophylactic Use of Oral Acetaminophen or IV Dexamethasone and Combination of them on Prevention Emergence Agitation in Pediatric after Adenotonsillectomy

    Directory of Open Access Journals (Sweden)

    Parvin Sajedi

    2014-01-01

    Full Text Available Background: The present study was aimed to evaluate the efficacy of acetaminophen plus dexamethasone on post-operative emergence agitation in pediatric adenotonsillectomy. Methods: A total of 128 patients were randomized and assigned among four groups as: Intravenous (IV dexamethasone, oral acetaminophen, IV dexamethasone plus oral acetaminophen, placebo. Group 1 received 0.2 mg/kg dexamethasone plus 0.25 mg/kg strawberry syrup 2 h before surgery. Group 2 received 20 mg/kg oral acetaminophen (0.25 ml/kg with 0.05 ml/kg IV normal saline. Group 3 received 20 mg/kg acetaminophen and 0.2 mg/kg dexamethasone intravenously. Group 4 received 0.25 ml/kg strawberry syrup and 0.05 ml/kg normal saline. Agitation was measured according to Richmond agitation sedation score in the post anesthetic care unit (PACU after admission, 10, 20 and 30 min after extubation. Pain score was measured with FACE scale. Nurse satisfaction was measured with verbal analog scale. If agitation scale was 3 ≥ or pain scale was 4 ≥ meperidine was prescribed. If symptoms did not control wit in 15 min midazolam was prescribed. Patients were discharged from PACU according Modified Alderet Score. Data were analyzed with ANOVA, Chi-square, and Kruskal-Wallis among four groups. P < 0.05 was considered statistically significant. Results: A total of 140 patients were recruited in the study, which 12 of them were excluded. Thus, 128 patients were randomized and assigned among four groups. The four treatment groups were generally matched at baseline data. Median of pain score in 0, 10, 20 and 30 min after extubation were different between each study group with the control group (<0.001, 0.003 respectively. Also median of agitation score in 0, 10, 20 and 30 min after extubation were different between each study group with the control group (<0.001. Incidence of pain and incidence of agitation after extubation were not statistically identical among groups (P < 0.001 and P = 0

  20. Solubilization of proteins in aqueous two-phase extraction through combinations of phase-formers and displacement agents.

    Science.gov (United States)

    Kress, Christian; Sadowski, Gabriele; Brandenbusch, Christoph

    2017-03-01

    The aqueous two-phase extraction (ATPE) of therapeutic proteins is a promising separation alternative to cost-intensive chromatography, still being the workhorse of nowadays downstream processing. As shown in many publications, using NaCl as displacement agent in salt-polymer ATPE allows for a selective purification of the target protein immunoglobulin G (IgG) from human serum albumin (HSA, represents the impurity). However a high yield of the target protein is only achievable as long as the protein is stabilized in solution and not precipitated. In this work the combined influence of NaCl and polyethylene glycol (Mw=2000g/mol) on the IgG-IgG interactions was determined using composition gradient multi-angle light scattering (CG-MALS) demonstrating that NaCl induces a solubilization of IgG in polyethylene glycol 2000 solution. Moreover it is shown that the displacement agent NaCl has a significant and beneficial influence on the IgG solubility in polyethyleneglycol2000-citrate aqueous two-phase system (ATPS) which can also be accessed by these advanced B22 measurements. By simultaneous consideration of IgG solubility data with results of the ATPS phase behavior (especially volume fraction of the respective phases) allows for the selection of process tailored ATPS including identification of the maximum protein feed concentration. Through this approach an ATPS optimization is accessible providing high yields and selectivity of the target protein (IgG).

  1. 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.

  2. The Impact of Nonpolymerizable Swelling Agents On The Synthesis of Particles With Combined Geometric, Interfacial, and Compositional Anisotropy.

    Science.gov (United States)

    Wang, Sijia; Wu, Ning

    2015-07-28

    Seeded emulsion polymerization is by far the most successful synthetic method for making anisotropic particles with precise control and high throughput. However, this synthesis involves multiple steps and the types of anisotropic properties that have been made on particles are limited. Here, we demonstrate, by using two different types of nonpolymerizable swelling agents, that we can simplify this method while still producing colloidal dimers with combined anisotropic properties in geometry, interface, and composition. When we swell cross-linked polystyrene seed particles with a simple solvent toluene, without additional polymerization steps we can make dimers with asymmetric distribution of surface charges and roughness on two lobes by fast extraction of toluene. We further show that this toluene-swelling-extraction method can promote the surface modification of the second lobe selectively especially for hydrophilic and stimuli-responsive polymers, which was a significant challenge in dimer synthesis. When we change the swelling agent to a sol-gel precursor, that is, tetraethyl orthosilicate, we can make polystyrene-silica hybrid particles with different morphologies. Our method provides a facile synthetic platform for making colloidal particles with different types of anisotropic properties, which are expected to find important applications for colloidal surfactant, self-assembly, and artificial motors.

  3. Effectiveness and acceptability of progestogens in combined oral contraceptives – a systematic review

    Directory of Open Access Journals (Sweden)

    Kulier Regina

    2004-06-01

    Full Text Available Abstract Background The progestogen component of oral contraceptives (OCs has undergone changes since it was recognized that their chemical structure can influence the spectrum of minor adverse and beneficial effects. Methods The objective of this review was to evaluate currently available low-dose OCs containing ethinylestradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates. The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases were searched. Randomized trials reporting clinical outcomes were considered for inclusion and were assessed for methodological quality and validity. Results Twenty–two trials were included in the review. Eighteen were sponsored by pharmaceutical companies and in only 5 there was an attempt for blinding. Most comparisons between different interventions included one to three trials, involving usually less than 500 women. Discontinuation was less with second-generation progestogens compared to first–generation (RR 0.79; 95% CI 0.69–0.91. Cycle control appeared to be better with second-compared to first-generation progestogens for both, mono-and triphasic preparations (RR 0.69; 95% CI 0.52–0.91 and (RR 0.61; 95% CI 0.43–0.85, respectively. Intermenstrual bleeding was less with third- compared to second-generation pills (RR 0.71; 95% CI 0.55–0.91. Contraceptive effectiveness of gestodene (GSD was comparable to that of levonorgestrel (LNG, and had similar pattern of spotting, breakthrough bleeding and absence of withdrawal bleeding. Drospirenone (DRSP was similar compared to desogestrel (DSG regarding contraceptive effectiveness, cycle control and side effects. Conclusion The third- and second-generation progestogens are preferred over first generation in all indices of acceptability. Current evidence suggests that GSD is comparable to LNG in terms of contraceptive effectiveness and for most cycle control indices. GSD is also

  4. Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents.

    Science.gov (United States)

    Fang, Lei; Chen, Mohao; Liu, Zhikun; Fang, Xubin; Gou, Shaohua; Chen, Li

    2016-02-15

    In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid-carbazole hybrid compounds were designed and synthesized. Ellman's assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture.

  5. A comparative study to evaluate the effect of intranasal dexmedetomidine versus oral alprazolam as a premedication agent in morbidly obese patients undergoing bariatric surgery

    Directory of Open Access Journals (Sweden)

    Lakshmi Jayaraman

    2013-01-01

    Full Text Available Background: Morbidly obese patients with obstructive sleep apnea are extremely sensitive to sedative premedication. Intranasal dexmedetomidine is painless and quick acting. Intranasal dexmedetomidine can be used for premedication as it produces adequate sedation and also obtund hemodynamic response to laryngoscopy and tracheal intubation. Materials and Methods: Forty morbidly obese patients with BMI > 35 were chosen and divided into two groups. Group DEX received intranasal dexmedetomidine 1 mcg/kg (ideal body weight while other group (AZ received oral alprazolam 0.5 mg. Sedation scale, heart rate and the mean arterial pressure was assessed in both the groups at 0 hour, 45 minutes, during laryngoscopy and tracheal intubation. Results: The demographic profile, baseline heart rate, means arterial pressure, oxygen saturation and sedation scale was comparable between the two groups. The sedation scores, after 45 min, were statistically significant between the two groups i.e., 2.40 ± 1.09 in the AZ group as compared to 3.20 ± 1.79 in DEX group P value 0.034. The heart rate, mean arterial pressure and oxygen saturation were statistically similar between the two groups, after 45 min. The heart rate was significantly lower in the DEX group as compared to the AZ group. There was no statistical difference in the mean arterial pressure between the two groups either during laryngoscopy or tracheal intubation. Conclusion: Intranasal dexmedetomidine is a better premedication agent in morbidly obese patients than oral alprazolam.

  6. A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease.

    Science.gov (United States)

    Kutlar, Abdullah; Ataga, Kenneth I; McMahon, Lillian; Howard, Joanna; Galacteros, Frederic; Hagar, Ward; Vichinsky, Elliott; Cheung, Anthony T W; Matsui, Neil; Embury, Stephen H

    2012-05-01

    Abnormal blood flow accounts for most of the clinical morbidity of sickle cell disease (SCD) [1,2]. Most notably, occlusion of flow in the microvasculature causes the acute pain crises [3] that are the commonest cause for patients with SCD to seek medical attention [4] and major determinants of their quality of life [5]. Based on evidence that endothelial P-selectin is central to the abnormal blood flow in SCD we provide results from four of our studies that are germane to microvascular blood flow in SCD. A proof-of-principle study established that doses of heparin lower than what are used for anticoagulation but sufficient to block P-selectin improved microvascular blood flow inpatients with SCD. An in vitro study showed that Pentosan Polysulfate Sodium (PPS) had greater P-selectin blocking activity than heparin. A Phase I clinical study demonstrated that a single oral dose of PPS increased microvascular blood flow in patients with SCD. A Phase II clinical study that was not completed documented that daily oral doses of PPS administered for 8 weeks lowered plasma levels of sVCAM-1 and tended to improve microvascular blood flow in patients with SCD. These data support the concept that P-selectin on the microvascular endothelium is critical to both acute vascular occlusion and chronically impaired microvascular blood flow in SCD. They also demonstrate that oral PPS is beneficial to microvascular sickle cell blood flow and has potential as an efficacious agent for long-term prophylactic therapy of SCD.

  7. Efficient mucus permeation and tight junction opening by dissociable "mucus-inert" agent coated trimethyl chitosan nanoparticles for oral insulin delivery.

    Science.gov (United States)

    Liu, Min; Zhang, Jian; Zhu, Xi; Shan, Wei; Li, Lian; Zhong, Jiaju; Zhang, Zhirong; Huang, Yuan

    2016-01-28

    Oral administration of protein drugs is greatly impeded by the lack of drug carriers that can efficiently overcome the absorption barriers of mucosa tissue, which consists of not only epithelium but also a blanket of mucus gel. We herein report a novel self-assembled nanoparticle (NP) platform for oral delivery of insulin by facilitating the efficient permeation through both of these two barriers. The NP possesses a core composed of insulin and trimethyl chitosan (TMC), and a dissociable "mucus-inert" hydrophilic coating of N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) derivative. The NPs exhibited free Brownian motion and excellent permeability in mucus, which enabled the access of the NP core to the epithelial cell surface underneath the mucus. Moreover, investigation of NP behavior showed that the pHPMA molecules started to dissociate as the NP permeates through mucus, and the TMC NP core was then exposed to facilitate transepithelial transport via paracellular pathway. The pHPMA coating significantly improved transepithelial transport of TMC-based NP and their ability to open tight junctions between the mucus-secreting epithelial cells. Moreover, in diabetic rats, pHPMA coated NPs generated a prominent hypoglycemic response following oral administration, and exhibited a relative bioavailability 2.8-fold higher than that of uncoated TMC-based NPs. Our study provided the evidence of using pHPMA as "mucus-inert" agent to enhance mucus permeation of TMC-based NPs, and validated a novel strategy to overcome the multiple absorption barriers using NP platform with dissociable hydrophilic coating and TMC-based core possessing tight junction-opening ability.

  8. In vitro activity of lauric acid or myristylamine in combination with six antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Kitahara, Takashi; Aoyama, Yuko; Hirakata, Yoichi; Kamihira, Shimeru; Kohno, Shigeru; Ichikawa, Nobuhiro; Nakashima, Mikiro; Sasaki, Hitoshi; Higuchi, Shun

    2006-01-01

    The objective of this study was to investigate the in vitro activities of lauric acid and myristylamine in combination with six antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA). The combination effect of lipids and antimicrobial agents was evaluated by the checkerboard method to obtain a fractional inhibitory concentration (FIC) index. The effects of lauric acid + gentamicin (GM) and lauric acid + imipenem (IPM) combinations were synergistic against the clinical isolates in 12 combinations. An antagonistic FIC index was observed only with the myristylamine + GM combination. We investigated in detail the antimicrobial activity for two combinations that showed a synergistic effect. The cytotoxicity of lauric acid was not enhanced by the addition of GM and IPM. In time-kill studies, lauric acid + GM and lauric acid + IPM combinations at one-eighth of the minimum inhibitory concentration produced a bacteriostatic effect.

  9. Bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a fixed-combination syrup versus an oral reference product

    National Research Council Canada - National Science Library

    Janin, Annick; Monnet, Joelle

    2014-01-01

    Objectives The primary objective of this study was to compare the bioavailability of paracetamol, phenylephrine hydrochoride and guaifenesin in a new oral syrup with an established oral reference product...

  10. Field Evaluation of the Effectiveness of an Oral Toltrazuril and Iron Combination (Baycox® Iron) in Maintaining Weaning Weight by Preventing Coccidiosis and Anaemia in Neonatal Piglets.

    Science.gov (United States)

    Streyl, Kristina; Carlstron, Janaina; Dantos, Eliana; Mendoza, Roberto; Islas, Juan Agustin Torres; Bhushan, Chandra

    2015-08-01

    Effectiveness of an oral combination of toltrazuril and iron dextran (Baycox(®) Iron) to maintain weaning weight by preventing coccidiosis caused by Isospora suis and iron-deficiency anaemia in neonatal piglets was investigated on three commercial pig farms with a history of coccidiosis: two in Mexico and one in Brazil. On day (SD) 2 of life, piglets were randomised within litter by bodyweight to treatment or control group. On SD 3 piglets allocated to the control group (CG) each received 1 mL Baycox(®), containing 50 mg/mL toltrazuril orally and commercially available iron (200 mg/piglet) by intramuscular injection. Piglets allocated to the treatment group (TG) each received 1 mL toltrazuril and iron combination orally (Baycox(®) Iron) containing 50 mg/mL toltrazuril and 228 mg iron as iron dextran. All piglets had access to creep feed. 6493 piglets completed the study. Bodyweight at weaning on SD 21 of piglets treated with the oral toltrazuril and iron combination was confirmed to be non-inferior to the control treatment with coccidiosis. Haemoglobin levels on SD 21 were lower in the oral toltrazuril and iron combination treated piglets compared to control levels but above minimum haemoglobin levels to maintain health. There was no difference in mortality between the two groups. This large scale field evaluation clearly demonstrated the effectiveness of a combination of oral toltrazuril and iron (Baycox(®) Iron) in maintaining body weight at weaning compared to conventional treatment. The combination was effective in preventing coccidiosis and anaemia and thus provides a valuable alternative that reduces stressful events in neonatal piglets. There were no product related adverse events.

  11. Cardiovascular risk in Egyptian healthy consumers of different types of combined oral contraceptives pills: A comparative study.

    Science.gov (United States)

    El-Haggar, Sahar M; Mostafa, Tarek M

    2015-08-01

    This study aimed to evaluate the associated cardiovascular risk in Egyptian healthy consumers of different types of combined oral contraceptives pills (COCPs) via determination of lipids profiles, Castelli index I, leptin, adiponectin, and resistin concentrations as cardiovascular risk factors. In this cross-sectional study, the study groups consisted of control group that represented by 30 healthy married women who were not on any contraceptive mean or any hormonal therapy and had normal menstrual cycles, group two consisted of 30 women who were users of Levonorgesterl 0.15 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, group three consisted of 30 women who were users of Gestodene 0.075 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, and group four consisted of 30 women who were users of Drospirenone 3 mg plus Ethinylestradiol 0.03 mg as 21 days cycle. One-way analysis of variance followed by LSD post hoc test was used for comparison of variables. P value index. Formulation containing ethinylestradiol combined with gestodene neither altered adipose tissue function nor showed deleterious effect on lipid panel. Formulation containing ethinylestradiol combined with drospirenone resulted in significantly higher HDL-C and adiponectin concentrations. In conclusion, the uptake of COCPs containing levonorgestrel plus ethinylestradiol is associated with high cardiovascular risk since this formulation showed significantly lower adiponectin concentration, significantly higher leptin, resistin, and atherogenic index as compared to other studied groups. By contrast, the formulations containing ethinylestradiol combined with third generation progestin gestodene or fourth generation progestin drospirenone are associated with low cardiovascular risk since they neither altered adipose tissue function nor impaired lipoprotein metabolism as experienced by their favorable effect on leptin, adiponectin, and resistin, with non-changed atherogenic index, higher HDL-C levels and

  12. 我院门诊口服降糖药应用情况分析%Analysis on Usage of Oral Hypoglycemic Agents by Outpatient in the Hospital

    Institute of Scientific and Technical Information of China (English)

    姜鹏; 鲁薇; 张少华

    2014-01-01

    Objective:To analyze the use of oral hypoglycemic agents by outpatient in the hospital during 2010~2012 , so as to pro-vide preference for clinical rational drug use.Methods:The information of various types of oral hypoglycemic by outpatient during 2010~2012 from the HIS system was obtained , the using frequency and cost per day were statistically analyzed and compared.Results:Acar-bose of sales amount for three consecutive years first row.Metformin of use frequency increased year by year , 2 years in first row, and the cost per day minimum.The serial number ratio greater than 1 is metformin.Conclusion:The use of oral hypoglycemic agent in the hospi-tal is reasonable , metformin of use frequency is high , conform to the principle of safe , effective and economic medication.%目的:分析我院2010~2012年门诊口服降糖药物的应用情况,为临床合理用药提供参考。方法:从HIS系统中调取2010~2012年中门诊各类口服降糖药物的使用数据,对其使用频率、日均费用等进行对比分析。结果:阿卡波糖销售金额连续3年排首位;二甲双胍的使用频率逐年上升,连续2年位居第一,且日平均费用最低;序号比大于1的药物为二甲双胍。结论:该院口服降糖药物的应用基本合理,二甲双胍使用频率高,符合安全、有效、经济的用药原则。

  13. Effectiveness on oral pain of 808-nm diode laser used prior to composite restoration for symptomatic non-carious cervical lesions unresponsive to desensitizing agents.

    Science.gov (United States)

    Femiano, Felice; Femiano, Rossella; Lanza, Alessandro; Lanza, Michele; Perillo, Letizia

    2017-01-01

    This study compares sensitivity reduction after dental restoration with and without prior diode laser (DL) irradiation for cervical dentine hypersensitivity (CDH) from non-carious cervical lesions (NCCLs) unresponsive to desensitizing agents. Eighty-eight teeth of 28 subjects (21 females; age 23-64 years), with CDH from NCCL were included in this study. NCCLs of each oral quadrant were randomized in two groups (study group (SG)) to estimate the sensitivity reduction after dental restoration (SG-1) compared with the DL irradiation used prior to restoration placement (SG-2). The subjects were asked to rate the sensitivity experienced during air stimulation using a visual analog scale before (baseline), immediately after, and at 6 and 12 months from restoration. The outcomes showed a significant reduction of discomfort compared to baseline for NCCLs of SG-2 with the decrease of 78.5, 78.9, and 78.1 % immediately and at 6 and 12 months after restoration, respectively; in comparison with the decrease of 70.1, 67, and 65.3 % for NCCLs of SG-1 immediately and at 6 and 12 months after restoration, respectively; and compared to baseline. The DL irradiation prior to dental restoration can further improve the painful symptomatology of CDH from NCCL unresponsive to desensitizing agents.

  14. Pharmacokinetic overview of ethinyl estradiol dose and bioavailability using two transdermal contraceptive systems and a standard combined oral contraceptive

    Science.gov (United States)

    Hofmann, Birte; Reinecke, Isabel; Schuett, Barbara; Merz, Martin; Zurth, Christian

    2014-01-01

    Objective: To determine the relative bioavailability of ethinyl estradiol (EE) and gestodene (GSD) after application of a novel transdermal contraceptive patch vs. a standard combined oral contraceptive (COC) pill (study 1), and to evaluate the pharmacokinetics (PK) of EE after application of the EE/GSD patch compared with an EE/norelgestromin (NGMN) patch (study 2). Materials: Participants were healthy, non-obese women aged 18 – 45 years (study 1) or 18 – 35 years (study 2). Compositions of study treatments were as follows: 0.55 mg EE/2.1 mg GSD (EE/GSD patch); 0.02 mg EE/0.075 mg GSD (standard COC); 0.6 mg EE/6 mg NGMN (EE/NGMN patch). Methods: In study 1, which consisted of 3 treatment periods (each followed by 7 patch- or pill-free days), treatments were administered in one of two randomized orders: either P–M–E (EE/GSD patch (P) every 7 days for 28 days → COC (M) once-daily for 21 days → two 7-day patch-wearing periods followed by one 10-day patch-wearing phase (E)), or the same treatments administered in sequence M–P–E. For study 2, participants received either the EE/GSD patch or EE/NGMN patch for seven treatment cycles (one patch per week for 3 weeks followed by a 7-day patch-free interval). Results: In study 1, average daily exposure to EE was similar for treatments P and M; the mean daily area under the concentration-time curve (AUC) ratio of treatment P vs. treatment M for EE was 1.06 (90% confidence interval (CI): 0.964 – 1.16), indicating average daily delivery similar to oral administration of 0.019 – 0.023 mg EE. For unbound GSD, average daily exposure was lower for treatment P vs. treatment M. The mean AUC ratio of treatment P vs. treatment M for unbound GSD was 0.820 (90% CI: 0.760 – 0.885), indicating average daily delivery from the patch of 0.057 – 0.066 mg GSD. Prolonged patch wearing did not result in a distinct decline in GSD and EE serum concentrations. In study 2, AUC at steady state (AUC0–168,ss

  15. Antifertility Effects of Orally Administration of Low Dose Gossypol Acetic Acid Combined with Methyltestosterone Plus Ethinyl Estradiol on Male Rat

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To investigate the feasibility and optimal regimen of orally administration of low close gossypol acetic acid (GA) combined with methyltestosterone (MT) plus ethinyl estradiol (EE) for contraception in males.Methods Wistar male rats were randomly assigned into four groups, 20 in each group. Animals in group A or B were administered daily with 1% methyl cellulose or GA (12 mg/kg) suspended in 1% methyl cellulose, respectively. Rats in group C or D took firstly GA 12 mg/kg+MT 20 mg/kg+EE 0.1 mg/kg or MT 20 mg/kg+EE 0.1 mg/kg, in a suspension with 1% methyl cellulose, via gastric intubation. After the infertilities were initiated(6 weeks for group C, 8 weeks for group D), GA was served alone while MT+EE were withdrawn in rats of groups C and D. The treatment was ceased after 18 weeks and some males from group C were permitted to recover. Fertility testing, 10 males per group, was served for determining infertility or restoration of fertility in treated rats. Examinations of histology and biochemistry in treated rats were used to examine the morphologic influences on sperm, testis, epididymides and viscera, and biochemical changes in blood. The growth and development of F1 generation of the rats would also be tested in a series of behavioral tests.Results Ten rats from group C were infertile at week 6 after treatment, and the fulfilled infertility was maintained with low-close GA (12 mg/kg) only daily. Six weeks after cessation of treatment, all of treated males recovered their fertility. However, 8 of 10 rats from group D were in sterility at 6th week of treatment and all at 8th week of treatment, but the infertility could not be kept with the similar dose GA alone later on. Moreover, no adverse effects were found in our present experiments.Conclusion Administration of oral low dose GA combined with MT and EE as loading dose could successfully induce infertility in short term, whereafter the efficacy could completely be maintained by similar low dose of GA

  16. Different Effects of Myoinositol plus Folic Acid versus Combined Oral Treatment on Androgen Levels in PCOS Women

    Directory of Open Access Journals (Sweden)

    Ali Cenk Ozay

    2016-01-01

    Full Text Available Recently, myoinositol (myo-ins and folic acid combination has gained an important role for treating Polycystic Ovary Syndrome (PCOS, in addition to combined oral contraceptives (COC. We aimed to examine myo-ins effects on anti-Mullerian hormone (AMH levels and compare them with those ones obtained administering COC. In this prospective study, 137 PCOS patients, diagnosed according to Rotterdam criteria and admitted to the Reproductive Endocrinology and Infertility Outpatient Clinic at Dokuz Eylul University (Izmir, Turkey, were included. After randomization to COC (n=60 and myo-ins (n=77 arms, anthropometric measurements, blood pressure, Modified Ferriman Gallwey scores were calculated. Biochemical and hormonal analysis were performed, and LH/FSH and Apo B/A1 ratios were calculated. Data analysis was carried out in demographically and clinically matched 106 patients (COC = 54; myo-ins = 52. After 3-month treatment, increase in HDL and decreases in LH and LH/FSH ratio were statistically more significant only in COC group when compared with baseline (in both cases p>0.05. In myo-ins group, fasting glucose, LDL, DHEAS, total cholesterol, and prolactin levels decreased significantly (for all p<0.05. Progesterone and AMH levels, ovarian volume, ovarian antral follicle, and total antral follicle counts lessened significantly in both groups (for all p<0.05. In PCOS treatment, MYO is observed more effective in reductions of total ovarian volume and AMH levels.

  17. Different Effects of Myoinositol plus Folic Acid versus Combined Oral Treatment on Androgen Levels in PCOS Women

    Science.gov (United States)

    Emekci Ozay, Ozlen; Okyay, Recep Emre; Cagliyan, Erkan; Kume, Tuncay; Gulekli, Bulent

    2016-01-01

    Recently, myoinositol (myo-ins) and folic acid combination has gained an important role for treating Polycystic Ovary Syndrome (PCOS), in addition to combined oral contraceptives (COC). We aimed to examine myo-ins effects on anti-Mullerian hormone (AMH) levels and compare them with those ones obtained administering COC. In this prospective study, 137 PCOS patients, diagnosed according to Rotterdam criteria and admitted to the Reproductive Endocrinology and Infertility Outpatient Clinic at Dokuz Eylul University (Izmir, Turkey), were included. After randomization to COC (n = 60) and myo-ins (n = 77) arms, anthropometric measurements, blood pressure, Modified Ferriman Gallwey scores were calculated. Biochemical and hormonal analysis were performed, and LH/FSH and Apo B/A1 ratios were calculated. Data analysis was carried out in demographically and clinically matched 106 patients (COC = 54; myo-ins = 52). After 3-month treatment, increase in HDL and decreases in LH and LH/FSH ratio were statistically more significant only in COC group when compared with baseline (in both cases p > 0.05). In myo-ins group, fasting glucose, LDL, DHEAS, total cholesterol, and prolactin levels decreased significantly (for all p < 0.05). Progesterone and AMH levels, ovarian volume, ovarian antral follicle, and total antral follicle counts lessened significantly in both groups (for all p < 0.05). In PCOS treatment, MYO is observed more effective in reductions of total ovarian volume and AMH levels. PMID:27882049

  18. Combination therapy of gemcitabine or oral S-1 with the anti-VEGF monoclonal antibody bevacizumab for pancreatic neuroendocrine carcinoma.

    Science.gov (United States)

    Kasuya, Kazuhiko; Nagakawa, Yuichi; Suzuki, Minako; Suzuki, Yoshiaki; Kyo, Bunso; Suzuki, Satoru; Matsudo, Takaaki; Itoi, Takao; Tsuchida, Akihiko; Aoki, Tatsuya

    2012-04-01

    We previously reported that the administration of bevacizumab for pancreatic neuroendocrine tumors inhibited angiogenesis in the host, resulting in tumor growth inhibition. In light of these results, we compared the effect of bevacizumab/gemcitabine/S-1 combination therapy vs. bevacizumab monotherapy. The QGP-1 pancreatic neuroendocrine carcinoma cell line and the BxPC-3 ductal cell carcinoma cell line were transplanted into the subcutaneous tissue of mice, and the mice were treated for 3 weeks with bevacizumab [50 mg/kg intraperitoneally (i.p.) twice weekly], gemcitabine (240 mg/kg i.p. once weekly) and S-1 (10 mg/kg orally five times weekly). The antitumor effect and side effects were evaluated by measuring the tumor volume and weight and by changes in body weight, respectively. The tumor volume became smaller (from the maximum volume) in the group treated with bevacizumab, gemcitabine and S-1 (BGS) and the group treated with bevacizumab and gemcitabine (BG). A significant difference was noted in the tumor weight between the BG group and the group treated with bevacizumab alone. A relatively significant decrease in the body weight was observed in the BGS and BG groups. We conclude that gemcitabine is appropriate as a drug used in combination with bevacizumab for pancreatic neuroendocrine tumors.

  19. Effect of Combination of Steel Fiber and MgO-type Expansive Agent on Properties of Concrete

    Institute of Scientific and Technical Information of China (English)

    WANG Aiguo; DENG Min; SUN Daosheng; MO Liwu; WANG Jun; TANG Mingshu

    2011-01-01

    The effect of combination of steel fiber and MgO-type expansive agent(MEA)on strength,air-permeability and porosity of concrete was investigated.The porosity and air-permeability of concrete were determined by method of evaporated water and Torrent permeability tester,respectively.Pore structures of mortars in concrete were analyzed using mercury intrusion porosimetry(MIP).Interfacial structures between steel fibers and matrix were examined by use of optical microscope.The experimental results show that improvement of pore structures of mortar and fiber-matrix interfacial structure in concrete by combination of steel fiber and MEA may remarkably increase properties of concrete.In comparison with plain concrete,compressive strength and splitting tensile strength of steel fiber reinforced expansive concrete increased by 15.3% and 38.1%,permeability coefficient K(t),penetration depth L and porosity of concrete decreased by 41.1%,21.3% and 13.1% at 28 days,respectively.

  20. Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor.

    Science.gov (United States)

    DeFronzo, R A; Chilton, R; Norton, L; Clarke, G; Ryder, R E J; Abdul-Ghani, M

    2016-05-01

    The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM.

  1. Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation.

    Science.gov (United States)

    Copelan, Edward A; Avalos, Belinda R; Ahn, Kwang Woo; Zhu, Xiaochun; Gale, Robert Peter; Grunwald, Michael R; Hamadani, Mehdi; Hamilton, Betty K; Hale, Gregory A; Marks, David I; Waller, Edmund K; Savani, Bipin N; Costa, Luciano J; Ramanathan, Muthalagu; Cahn, Jean-Yves; Khoury, H Jean; Weisdorf, Daniel J; Inamoto, Yoshihiro; Kamble, Rammurti T; Schouten, Harry C; Wirk, Baldeep; Litzow, Mark R; Aljurf, Mahmoud D; van Besien, Koen W; Ustun, Celalettin; Bolwell, Brian J; Bredeson, Christopher N; Fasan, Omotayo; Ghosh, Nilanjan; Horowitz, Mary M; Arora, Mukta; Szer, Jeffrey; Loren, Alison W; Alyea, Edwin P; Cortes, Jorge; Maziarz, Richard T; Kalaycio, Matt E; Saber, Wael

    2015-03-01

    Cyclophosphamide (Cy) in combination with busulfan (Bu) or total body irradiation (TBI) is the most commonly used myeloablative conditioning regimen in patients with chronic myeloid leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CML in first chronic phase after myeloablative conditioning with Cy in combination with TBI, oral Bu, or intravenous (i.v.) Bu. Four hundred thirty-eight adults received human leukocyte antigen (HLA)-matched sibling grafts and 235 received well-matched grafts from unrelated donors (URD) from 2000 through 2006. Important differences existed between the groups in distribution of donor relation, exposure to tyrosine kinase inhibitors, and year of transplantation. In multivariate analysis, relapse occurred less frequently among patients receiving i.v. Bu compared with TBI (relative risk [RR], .36; P = .022) or oral Bu (RR, .39; P = .028), but nonrelapse mortality and survival were similar. A significant interaction was detected between donor relation and the main effect in leukemia-free survival (LFS). Among recipients of HLA-identical sibling grafts, but not URD grafts, LFS was better in patients receiving i.v. Bu (RR, .53; P = .025) or oral Bu (RR, .64; P = .017) compared with TBI. In CML in first chronic phase, Cy in combination with i.v. Bu was associated with less relapse than TBI or oral Bu. LFS was better after i.v. or oral Bu compared with TBI.

  2. Fusion proteins containing neuropeptides as novel insect contol agents: snowdrop lectin delivers fused allatostatin to insect haemolymph following oral ingestion.

    Science.gov (United States)

    Fitches, Elaine; Audsley, Neil; Gatehouse, John A; Edwards, John P

    2002-12-01

    The mannose-binding lectin from snowdrop (Galanthus nivalis agglutinin: GNA), when fed to insects, binds to the gut epithelium and passes into the haemolymph. The potential for GNA to act as a carrier protein to deliver an insect neuropeptide, Manduca sexta allatostatin (Manse-AS), to the haemolymph of lepidopteran larvae has been examined by expressing a GNA/Manse-AS fusion protein (FP) in Escherichia coli, and feeding purified FP to larvae of the tomato moth Lacanobia oleracea. FP, administered at 1.5 or 0.5% of dietary proteins, was found to strongly inhibit feeding and prevent growth of fifth stadium larvae, whereas neither GNA nor Manse-AS alone, nor a mixture of GNA and Manse-AS in control treatments, had deleterious effects at similar levels. Elevated levels of material reacting with anti-Manse-AS antibodies were detected in the haemolymph of insects fed diets containing FP, suggesting that transport of the peptide had occurred. Evidence for the delivery of intact FP to the haemolymph was provided by the co-elution of Manse-AS-like immunoreactivity with standard FP after size exclusion chromatography of haemolymph from FP-fed larvae. GNA/Manse-AS and similar fusion proteins offer a novel and effective strategy for delivering insect neuropeptides by oral administration, which could be used in conjunction with expression in transgenic plants to give crop protection in the field.

  3. Attenuation of obesity-induced inflammation in mice orally administered with salmon cartilage proteoglycan, a prophylactic agent.

    Science.gov (United States)

    Hirose, Shouhei; Asano, Krisana; Nakane, Akio

    2017-03-11

    Obesity is associated with chronic inflammation of adipose tissue and causes development of type 2 diabetes. M1 macrophage population was increased in adipose tissue of obese mouse. M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines. Our previous studies demonstrated that salmon cartilage proteoglycan (PG) suppresses excess inflammation in various mouse inflammatory diseases. In this study, we examined the effect of PG on type 2 diabetes using high-fat-diet (HFD) induced obese mouse model. Oral PG administration enhanced the population of small adipocytes (area less than 1000 μm(2)) without body and tissue weight gain. In addition, PG administration suppressed mRNA expression of TNF-α, IL-6 and CXCL2 in adipose tissue. The proportion of M1 macrophages was decreased by PG administration. In addition, PG administration suppressed hyperglycemia after intraperitoneal glucose injection. Fasted serum insulin level was decreased in PG-administered mice. Moreover, insulin-stimulated phosphorylation of Akt was enhanced in the liver and gastrocnemius skeletal muscle of PG-administered mice. These data suggested that PG administration improves hyperglycemia and insulin sensitivity in obese mice by modulation of M1 macrophages which secrete proinflammatory cytokines in adipose tissue and activation of Akt in liver and skeletal muscle.

  4. Retrospective Analysis of Application of Oral Hypoglycemic Agents in a Hospital of Chongqing in Recent 3 Years%重庆市某医院近3年口服降糖药应用分析

    Institute of Scientific and Technical Information of China (English)

    苏湲淇; 龙波

    2012-01-01

    Objective To analyze the application situation and the development trend of oral hypoglycemic agents in a grade A class 3 hospital of Chongqing. Methods The sale amount,DDDs and other indicators of the oral hypoglycemic agent application in the hospital during the year 2007-2009 were statistically analyzed. Results In the last three years,the hospital's total sales of oral hypoglycemic agents and the total amount of DDDs were increased year by year. Biguanide, a - glucosidase inhibitors, thiazolidinediones were mainly selected in clinical use. Conclusion The overall structure of hospital clinical use of oral hypoglycemic agents is reasonably stable.%目的 分析医院口服降糖药的应用情况与发展趋势.方法 对医院2007年至2009年口服降糖药的销售金额、用药频度等指标进行统计分析.结果 口服降糖药的总销售金额和总用药频度逐年增长,临床主要选用双胍类、α-葡萄糖苷酶抑制剂、噻唑烷二酮类药物.结论 口服降糖药临床用药整体结构合理稳定.

  5. 2008年至2010年我院口服降血糖药使用情况分析%Analysis on Use Status of Oral Hypoglycemic Agents in Our Hospital during 2008-2010

    Institute of Scientific and Technical Information of China (English)

    向光芳; 郑姣妮; 姜宁

    2012-01-01

    Objective To provide fundamental basis for rational use of medicines in clinic, we investigated the application of oral hypo-glycemic agents at our hospital. Methods The statistic analysis was carried out to study the use of oral hypoglycemic agents in our hospital during 2008 - 2010 using order of consumption sum and frequency degree analysis methods. Results Thiazolidinediones, a - glucosidase inhibitor and biguanides ranked the top three among all the oral hypoglycemic agents in consumption sum. The highest DDDs is rosiglita-zone, followed by glimepiride and acarbose. Conclusion The use of oral hypoglycemic agents in our hospital is basically reasonable.%目的 了解医院口服降血糖药的使用情况,为临床合理用药提供参考.方法 采用金额排序和频度分析法,对医院2008年至2010年口服降血糖药进行统计分析.结果 口服降糖药用药金额排前3位的分别是噻唑烷二酮类、a-糖苷酶抑制剂和双胍类;用药频度最高的是罗格列酮,其次是格列美脲和阿卡波糖.结论 医院口服降血糖药的使用基本合理.

  6. Effects of low-dose aspirin (50-mg/day), low-dose aspirin plus dipyridamole, and oral anticoagulant agents after internal mammary artery bypass-grafting : Patency and clinical outcome at 1 year

    NARCIS (Netherlands)

    van der Meer, J; de la Rivière, Aart Brutel; van Gilst, Wiek H.; Hillege, Hans L.; Pfisterer, M; Kootstra, G. J.; Dunselmann, P. H. J. M.; MULDER, BJM; Lie, Kong I.

    1994-01-01

    Objectives. This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anti coagulant agents in the prevention of internal mammary artery graft occlusion. Background. Antithrombotic drugs increase vein graft patency after coronary artery bypass

  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. 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.

  9. Treatment of Prolapse of Lumbar Intervertebral Disc by Tuina Massotherapy Combined with Oral Administration of Buyang Huanwu Tang——A Report of 75 Cases

    Institute of Scientific and Technical Information of China (English)

    Du Deli; Wang Xinzhong

    2007-01-01

    @@ Prolapse of lumbar intervertebral disc is a commonly encountered disease. From Feb. 2003 - Feb. 2005, a series of 75 cases had been treated by Tuina massotherapy combined with oral administration of Buyang Huanwu Tang (补阳还五汤 Decoction for Invigorating Yang and Recuperation), with satisfactory therapeutic results reported as follows.

  10. Interacción de los antineoplásicos orales con los alimentos: revisión sistemática Antineoplastic oral agents and drug-nutrient interactions: a sistematic review

    Directory of Open Access Journals (Sweden)

    N. V. Jiménez Torres

    2009-06-01

    cumplir estos estudios. Resultados: En la búsqueda inicial se obtuvieron 850 referencias (98,5% Medline + y 1,4% Cochrane. En la primera fase se excluyeron el 87,7% (746 de los artículos, correspondiendo el 100% a la búsqueda en Medline. En la segunda fase, quedaron 40 artículos (5,2% de los iniciales para su lectura crítica a texto completo, a los que se añadieron cuatro más no indexados en Medline. De la lectura crítica de los 44 artículos finales, se excluyeron 25 artículos (20 artículos originales, 4 comunicaciones cortas y 1 metanálisis por no incluir como medida de resultado el dictamen de bioequivalencia. Los 19 (2,2% artículos restantes proporcionaron información sobre 19 fármacos antineoplásicos orales, en 210 pacientes y 146 voluntarios sanos. De estos 19 fármacos, el 63% no presentan iFA o interacciones fármaco-alimento, pudiéndose administrar indistintamente con/sin alimentos; el 21% se deben administrar con alimentos y sólo el 16% presentan interacción fármaco alimento, por lo que se deben administrar sin alimentos. Discusión: Actualmente, la importancia clínica de las interacciones fármaco alimento con antineoplásicos orales se identifica más directamente con la seguridad del paciente que con la efectividad del tratamiento. Ante el desarrollo de estos agentes orales, su irrupción en la terapia oncológica desplazando a la terapia parenteral, con costes mensuales de miles de euros, hay necesidad de realizar estudios farmacocinéticos y farmacodinámicos bien diseñados. Su objetivo debe de ser comparar su biodisponibilidad en presencia o ausencia de alimentos con la respuesta clínica. Mientras tanto, establecer recomendaciones para su administración en relación con los alimentos, es inconsistente para algunos de estos fármacos y su resultado incierto por la falta de estudios fundamentados en el dictamen de bioequivalencia establecido por la FDA.Introduction: studies on bioavailability are part of the clinical development of

  11. EFFICACY AND SAFETY OF DEFERASIROX WHEN COMPARED TO D EFERIPRONE AS ORAL IRON CHELATING AGENT : A RANDOMIZED CONTROL TRIAL

    Directory of Open Access Journals (Sweden)

    Sanjeeva

    2015-03-01

    Full Text Available BACKGROUND : Thalassemia is one of the most common inherited hemoglobinopathy seen in southern India. With regular blood transfusion, these children live longer but associated morbidity due to iron overload impairs the quality of life. We studied the efficacy and safety of new oral iron chelator, deferasirox, compared with deferiprone which was used for long time. MATERIAL AND METHODS : We cond ucted a prospective randomised control study, between January 2011 to June 2012 at thalassemia day care centre of Indira Gandhi I nstitute of C hild H ealth, Bengaluru. The children who were diagnosed as Thalassemia and receiving regular blood transfusion wit h serum ferritin levels more than 1000ng/ml and not receiving any chelation therapy were included in the study. These children were randomly divided into two groups as group 1 and group 2 by computer generated randomization. The children included in g roup 1 received Deferasirox and group 2 received Deferiprone as chelation therapy. The dosage of deferasirox was 20mg/kg/day once daily and that of deferiprone 75 mg/kg/day in three divided daily doses. The primary study outcome was to measure and compare the d ecrease in serum ferritin levels between the two study groups. The secondary outcome measures were to compare the side effect profiles among the two groups. RESULTS : We included 41 thalessemic children and 19 of them were included in group 1 (Deferasirox and 22 children in Group 2 (Deferiprone. At the end of study period of 18 months three children in group II discontinued therapy due to side effects, hence the remaining 19 were available for final analysis in group 2 whereas no drop outs in the group 1. During the study period, the serum ferritin decreased from 3261±2613ng/dl to 1586±766 ng/dl in group 1 as compared in group 2 from 4109±3153 ng/dl to 1743±1138 ng/dl (fig 2. This was also not statistically significant. In group 2, 68% of the children expe rienced adverse effect as compared

  12. Effect of Hormone Replacement Therapy (HRT and low-dose combined oral pill on skin thickness, lipid profile and blood chemistry of menopausal women

    Directory of Open Access Journals (Sweden)

    Ali Baziad

    2003-12-01

    Full Text Available This study to evaluate the effect of hormone replacement therapy ( HRT and low-dose combinated oral pill on skin thickness , lipid profile and blood chemistry on menopausal woman.This study was carried out in one year randomized prospective study. 36 women were divided into 18 women receiving HRT and the other 18 receiving low-dose oral pill. The result of this study showed an increase in skin thickness (collagen in both groups. But Those received low dose oral pill showed more . The increase of the skin thickness can prevent osteoporosis. The administration of HRT or low-dose oral pill could cause allteration in blood lipip profile and blood chemistry. But The changes were still within in normal limit. The administration of low-dose oral pill can be considered in postmeno-pausal women. (Med J Indones 2003; 12: 224-8Keywords: Hormone replacement therapy, low-dose oral pill, menopausal women, skin thickness, lipid profile, blood chemistry.

  13. RPR 107393, a potent squalene synthase inhibitor and orally effective cholesterol-lowering agent: comparison with inhibitors of HMG-CoA reductase.

    Science.gov (United States)

    Amin, D; Rutledge, R Z; Needle, S N; Galczenski, H F; Neuenschwander, K; Scotese, A C; Maguire, M P; Bush, R C; Hele, D J; Bilder, G E; Perrone, M H

    1997-05-01

    Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl pyrophosphate to form squalene and is the first committed step in sterol synthesis. A specific inhibitor of squalene synthase would inhibit cholesterol biosynthesis but not prevent the formation of other products of the isoprenoid pathway, such as dolichol and ubiquinone. RPR 107393 [3-hydroxy-3-[4-(quinolin-6-yl)phenyl]-1-azabicyclo[2-2-2]octane dihydrochloride] and its R and S enantiomers are potent inhibitors of rat liver microsomal squalene synthase, with IC50 values of 0.6 to 0.9 nM. One hour after oral administration to rats, RPR 107393 inhibited de novo [14C]cholesterol biosynthesis from [14C]mevalonate in the liver with an ED50 value of 5 mg/kg. Diacid metabolites of [14C]farnesyl pyrophosphate were identified after acid treatment of the livers of these animals. These results support in vitro data demonstrating that these compounds are inhibitors of squalene synthase. In rats, RPR 107393 (30 mg/kg p.o. b.i.d. for 2 days) reduced total serum cholesterol by RPR 107393 (20 mg/kg b.i.d.) reduced plasma cholesterol concentration by 50% after 1 week of administration; this was greater than the reduction observed with lovastatin or pravastatin, neither of which produced > 31% reduction in plasma cholesterol when administered for 1 week at a dose of 50 mg/kg b.i.d. The R and S enantiomers of RPR 107393 (20 mg/kg p.o. q.d. for 7 days) reduced plasma low density lipoprotein cholesterol by 50% and 43%, respectively, whereas high density lipoprotein cholesterol was unchanged. In summary, RPR 107393 is a potent inhibitor of squalene synthase. It is an orally effective hypocholesterolemic agent in rats and marmosets that has greater efficacy than lovastatin or pravastatin in the marmoset.

  14. The combination of SMAD4 expression and histological grade of dysplasia is a better predictor for the malignant transformation of oral leukoplakia.

    Science.gov (United States)

    Xia, Rong-Hui; Song, Xiao-Meng; Wang, Xiao-Jing; Li, Jiang; Mao, Li

    2013-01-01

    Oral leukoplakia (OL) is the most common premalignancy in the oral cavity and can progress to oral squamous cell carcinoma (OSCC). SMAD4 is a tumor suppressor implicated in multiple cancer types including OSCC. To assess the role of SMAD4 in oral leukoplakia malignant transformation, the authors investigated SMAD4 expression patterns in OL and OSCC using a highly specific antibody and correlated the patterns with the risk of malignant transformation oral leukoplakia. Immunohistochemistry and a quantitative imaging system were used to measure SMAD4 expression in OL from 88 OL patients, including 22 who later went through malignant transformation, and their OSCC counterpart. Forty-three (48.9%) of the 88 OL patients had strong SMAD4 expression. SMAD4 expression had no significant correlation with patients' clinicopathological parameters. Interestingly, 17 (39.5%) of the 43 OL lesions with strong SMAD4 expression went through malignant transformation whereas only 5 (11.1%) of the 45 OL lesions with weak SMAD4 expression did so (p = 0.002). The SMAD4 expression in OL was much higher than that in their OSCC counterpart. Kaplan-Meier analysis revealed that the combination of SMAD4 expression and histological grade of dysplasia (p = 0.007) is a better predictor for the malignant transformation of oral leukoplakia. In the multivariate analysis, both SMAD4 expression and grade of dysplasia were identified as independent factors for OL malignant transformation risk (p = 0.013 and 0.021, respectively). It was concluded that high SMAD4 expression may be indicative of an early carcinogenic process in OL and serve as an independent biomarker in assessing malignant transformation risk in patients with OL, and the combination of SMAD4 expression and histological grade of dysplasia is a better predictor for the malignant transformation of oral leukoplakia.

  15. 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.

  16. FGFR4 polymorphism, TP53 mutation, and their combinations are prognostic factors for oral squamous cell carcinoma.

    Science.gov (United States)

    Tanuma, Jun-Ichi; Izumo, Toshiyuki; Hirano, Masato; Oyazato, Yoshitaka; Hori, Fumiya; Umemura, Eri; Shisa, Hayase; Hiai, Hiroshi; Kitano, Motoo

    2010-03-01

    The genotype of the fibroblast growth factor receptor 4 (FGFR4) gene and TP53 mutation have been reported as prognostic factors for cancers of the head and neck, bladder, breast and colon. To determine whether they are applicable for oral squamous cell carcinoma (OSCC), we investigated these two genes in OSCC samples from 150 patients who had undergone radical surgery and in 100 cancer-free individuals. In OSCC, the FGFR4 Gly388Arg polymorphism and the presence or absence of mutation in TP53 did not show a significant association with the clinicopathological features of the tumors at surgery. However, the FGFR4 Arg388 allele, as well as mutations in TP53, was found to be closely associated with poor prognosis. Moreover, these two parameters synergistically affected the survival of OSCC patients. During 60 months of observation after radical surgery, a majority of patients with homozygous Arg388 FGFR4 plus mutated TP53 died of cancer, whereas >90% patients carrying homozygous Gly388 FGFR4 plus wild-type TP53 survived. Therefore, the FGFR4 Gly388Arg polymorphism and TP53 mutations, as well as their combinations, are excellent predictors of the prognosis for OSCC patients.

  17. New contraceptive eligibility checklists for provision of combined oral contraceptives and depot-medroxyprogesterone acetate in community-based programmes.

    Science.gov (United States)

    Stang, A.; Schwingl, P.; Rivera, R.

    2000-01-01

    Community-based services (CBS) have long used checklists to determine eligibility for contraceptive method use, in particular for combined oral contraceptives (COCs) and the 3-month injectable contraceptive depot-medroxyprogesterone acetate (DMPA). As safety information changes, however, checklists can quickly become outdated. Inconsistent checklists and eligibility criteria often cause uneven access to contraceptives. In 1996, WHO produced updated eligibility criteria for the use of all contraceptive methods. Based on these criteria, new checklists for COCs and DMPA were developed. This article describes the new checklists and their development. Several rounds of expert review produced checklists that were correct, comprehensible and consistent with the eligibility requirements. Nevertheless, field-testing of the checklists revealed that approximately half (48%) of the respondents felt that one or more questions still needed greater comprehensibility. These findings indicated the need for a checklist guide. In March 2000, WHO convened a meeting of experts to review the medical eligibility criteria for contraceptive use. The article reflects also the resulting updated checklist. PMID:10994285

  18. Combining spatial distribution with oral bioaccessibility of metals in smelter-impacted soils: implications for human health risk assessment.

    Science.gov (United States)

    Pelfrêne, Aurélie; Détriché, Sébastien; Douay, Francis

    2015-02-01

    Geostatistical analysis and GIS-based spatial mapping have been widely used for risk assessment of environmental pollution. The objectives of this study were to: (1) investigate the spatial variability of pseudototal concentrations of Cd, Pb, and Zn; (2) estimate the degree of contamination on the basis of pollution indexes; and (3) combine geostatistical analysis with oral bioaccessibility to better assess the population's exposure to metals in smelter-impacted soils. Implications for human health risks were assessed by considering soil as a contaminant source, a release mechanism of contaminated soil to the hands, ingestion as an exposure route, and metal bioaccessibility. The bioaccessibility data in the gastric (G) and gastrointestinal (GI) phases were integrated into the standard hazard quotient-based risk assessment method. Using pollution indices showed that the entire area studied was highly polluted in terms of soil metal concentrations. However, the spatial pattern of health risk levels did not coincide with the spatial distribution of the degree of soil contamination. Introducing the bioaccessible fraction of metals from soils into the exposure calculations resulted in a substantial decrease in calculated risk (HI, hazard index) and provided a more realistic estimate of exposure to the three metals. For the highly exposed population, 46% of the soils studied provided an HI-G > 1.0 and 15% provided an HI-GI > 1.0, suggesting probable adverse health effects in children. The present study highlights the importance of conducting studies taking into account metal bioaccessible values in risk assessment.

  19. LEVELS OF KEY CYTOKINES, MACROGLOBULINS AND THEIR SPECIFIC IMMUNE COMPLEXES IN BLOOD SERA OF WOMEN TAKING COMBINED ORAL CONTRACEPTIVES

    Directory of Open Access Journals (Sweden)

    V. N. Zorina

    2011-01-01

    Full Text Available Abstract. We investigated effects of combined oral contraceptives (COC containing low- and microdoses of estrogenic components upon serum levels of macroglobulin family proteins (alpha-2-macroglobulin, α2-MG, and pregnancy-associated alpha-2-glycoprotein, α2-PAG, their immune complexes with IgG, as well as concentrations of some cytokines (IL-1β, IL-6, TNFα, IFNγ. It was shown that cytokine levels did not differ with control, whereas α2-MG concentrations showed a time-dependent decrease in a group of women taking COC with microdoses of estrogens, and α2-PAG levels increased tenfold, independent on dosage and time of COC application. Meanwhile, contents of PAG-IgG complexes exhibits a gradual decrease, along with increase in MG-IgG. Considering PAG as a marker of normal and malignant proliferation, we suggest, that the levels of α2-PAG may be useful in monitoring of women taking COC, in order to predict high risk of pathological  proliferation  by  evaluation  of  individuals with  elevated  α2-PAG  levels.  (Med.  Immunol.,  2011, vol. 13, N 6, pp 635-638 

  20. Effect of a combined oral contraceptive containing 20 microg ethinyl estradiol and 75 microg gestodene on hemostatic parameters.

    Science.gov (United States)

    Aldrighi, José Mendes; De Campos, Luis Salvoni Carneiro; Eluf Gebara, Otávio Celso; Petta, Carlos Alberto; Bahamondes, Luis

    2006-01-01

    The effects of a combined oral contraceptive (COC) containing 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) on prothrombin activity (PA), activated partial thromboplastin time (APTT), thrombin time (TT), platelet number, fibrinogen, antithrombin III (ATIII), protein C, protein S and D-dimer were evaluated over 6 months in 23 young, healthy women. Laboratory assessments were performed prior to initiation of COC use (pretreatment) and after 3 and 6 months of use. Results showed no significant changes in fibrinogen, protein C, ATIII or D-dimer during COC use, compared with pretreatment values. The increase in platelet count, decreases in protein S level, PA and APTT, and the prolongation of TT were significant. In conclusion, the use of a COC containing 20 microg EE and 75 microg GSD did not cause any significant changes in the hemostatic parameters studied that could be suggestive of a higher prothrombotic risk. Further studies with a larger sample size are necessary in order to obtain conclusive data.

  1. Efficacy of Acupuncture versus Combined Oral Contraceptive Pill in Treatment of Moderate-to-Severe Dysmenorrhea: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Intira Sriprasert

    2015-01-01

    Full Text Available 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.

  2. Risk factors for venous thromboembolism in women under combined oral contraceptive. The PILl Genetic RIsk Monitoring (PILGRIM) Study.

    Science.gov (United States)

    Suchon, Pierre; Al Frouh, Fadi; Henneuse, Agathe; Ibrahim, Manal; Brunet, Dominique; Barthet, Marie-Christine; Aillaud, Marie-Françoise; Venton, Geoffroy; Alessi, Marie-Christine; Trégouët, David-Alexandre; Morange, Pierre-Emmanuel

    2016-01-01

    Identifying women at risk of venous thromboembolism (VTE) is a major public health issue. The objective of this study was to identify environmental and genetic determinants of VTE risk in a large sample of women under combined oral contraceptives (COC). A total of 968 women who had had one event of VTE during COC use were compared to 874 women under COC but with no personal history of VTE. Clinical data were collected and a systematic thrombophilia screening was performed together with ABO blood group assessment. After adjusting for age, family history, and type and duration of COC use, main environmental determinants of VTE were smoking (odds ratio [OR] =1.65, 95% confidence interval [1.30-2.10]) and a body mass index higher than 35 kg.m⁻² (OR=3.46 [1.81-7.03]). In addition, severe inherited thrombophilia (OR=2.13 [1.32-3.51]) and non-O blood groups (OR=1.98 [1.57-2.49]) were strong genetic risk factors for VTE. Family history poorly predicted thrombophilia as its prevalence was similar in patients with or without first degree family history of VTE (29.3% vs 23.9%, p=0.09). In conclusion, this study confirms the influence of smoking and obesity and shows for the first time the impact of ABO blood group on the risk of VTE in women under COC. It also confirms the inaccuracy of the family history of VTE to detect inherited thrombophilia.

  3. Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs.

    Science.gov (United States)

    Araújo, Francisca; Shrestha, Neha; Shahbazi, Mohammad-Ali; Liu, Dongfei; Herranz-Blanco, Bárbara; Mäkilä, Ermei M; Salonen, Jarno J; Hirvonen, Jouni T; Granja, Pedro L; Sarmento, Bruno; Santos, Hélder A

    2015-08-25

    Multifunctional tailorable composite systems, specifically designed for oral dual-delivery of a peptide (glucagon-like peptide-1) and an enzymatic inhibitor (dipeptidyl peptidase 4 (DPP4)), were assembled through the microfluidics technique. Both drugs were coloaded into these systems for a synergistic therapeutic effect. The systems were composed of chitosan and cell-penetrating peptide modified poly(lactide-co-glycolide) and porous silicon nanoparticles as nanomatrices, further encapsulated in an enteric hydroxypropylmethylcellulose acetylsuccinate polymer. The developed multifunctional systems were pH-sensitive, inherited by the enteric polymer, enabling the release of the nanoparticles only in the simulated intestinal conditions. Moreover, the encapsulation into this polymer prevented the degradation of the nanoparticles' modifications. These nanoparticles showed strong and higher interactions with the intestinal cells in comparison with the nonmodified ones. The presence of DPP4 inhibitor enhanced the peptide permeability across intestinal cell monolayers. Overall, this is a promising platform for simultaneously delivering two drugs from a single formulation. Through this approach peptides are expected to increase their bioavailability and efficiency in vivo both by their specific release at the intestinal level and also by the reduced enzymatic activity. The use of this platform, specifically in combination of the two antidiabetic drugs, has clinical potential for the therapy of type 2 diabetes mellitus.

  4. Switching Patients with Non-Dialysis Chronic Kidney Disease from Oral Iron to Intravenous Ferric Carboxymaltose: Effects on Erythropoiesis-Stimulating Agent Requirements, Costs, Hemoglobin and Iron Status

    Science.gov (United States)

    Toblli, Jorge Eduardo; Di Gennaro, Federico

    2015-01-01

    Background Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often receive an erythropoiesis-stimulating agent (ESA) and oral iron treatment. This study evaluated whether a switch from oral iron to intravenous ferric carboxymaltose can reduce ESA requirements and improve iron status and hemoglobin in patients with ND-CKD. Methods This prospective, single arm and single-center study included adult patients with ND-CKD (creatinine clearance ≤40 mL/min), hemoglobin 11–12 g/dL and iron deficiency (ferritin iron and ESA during 6 months prior to inclusion. Study patients received an intravenous ferric carboxymaltose dose of 1,000 mg iron, followed by a 6-months ESA/ ferric carboxymaltose maintenance regimen (target: hemoglobin 12 g/dL, transferrin saturation >20%). Outcome measures were ESA dose requirements during the observation period after initial ferric carboxymaltose treatment (primary endpoint); number of hospitalizations and transfusions, renal function before and after ferric carboxymaltose administration, number of adverse reactions (secondary endpoints). Hemoglobin, mean corpuscular volume, ferritin and transferrin saturation were measured monthly from baseline until end of study. Creatinine clearance, proteinuria, C-reactive protein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase bimonthly from baseline until end of study. Results Thirty patients were enrolled (age 70.1±11.4 years; mean±SD). Mean ESA consumption was significantly reduced by 83.2±10.9% (from 41,839±3,668 IU/patient to 6,879±4,271 IU/patient; pferric carboxymaltose-related adverse events were reported and no patient withdrew or required transfusions during the study. Conclusion Among patients with ND-CKD and stable normal or borderline hemoglobin, switching from oral iron to intravenous ferric carboxymaltose was associated with significant improvements in hematological and iron parameters and a significant reduction in ESA dose

  5. Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice.

    Directory of Open Access Journals (Sweden)

    Ghanashyam Sarikonda

    Full Text Available A recent type 1 diabetes (T1D clinical trial of rituximab (a B cell-depleting anti-CD20 antibody achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin with anti-CD3 antibody (a T cell-directed immunomodulator offers better protection than either entity alone, indicating that novel combination therapies that include a T1D-related autoantigen are possible. To accelerate the identification and development of novel combination therapies that can be advanced into the clinic, we have evaluated the combination of a mouse anti-CD20 antibody with either oral insulin or a proinsulin-expressing DNA vaccine. Anti-CD20 alone, given once or on 4 consecutive days, produced transient B cell depletion but did not prevent or reverse T1D in the NOD mouse. Oral insulin alone (twice weekly for 6 weeks was also ineffective, while proinsulin DNA (weekly for up to 12 weeks showed a trend toward modest efficacy. Combination of anti-CD20 with oral insulin was ineffective in reversing diabetes in NOD mice whose glycemia was controlled with SC insulin pellets; these experiments were performed in three independent labs. Combination of anti-CD20 with proinsulin DNA was also ineffective in diabetes reversal, but did show modest efficacy in diabetes prevention (p = 0.04. In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production.

  6. Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Osterlind, Kell; Rytter, Carsten

    2008-01-01

    BACKGROUND: Most chemotherapeutics are administrated intravenously (iv), but some are also available in an oral (po) formulation. This study was designed with the primary objective to estimate the patients' preference for po or iv vinorelbine in combination with carboplatin for the palliative.......001). The response rate was 23% and median survival 11.4 months. Patients with preference for po treatment stated that side effects were less with capsules and that daily life was less affected by capsules. CONCLUSION: Three out of four patients preferred oral vinorelbine. Clinical outcomes were comparable to other...

  7. 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.

  8. Combination therapy for erectile dysfunction: a randomized, double blind, unblinded active-controlled, cross-over study of the pharmacodynamics and safety of combined oral formulations of apomorphine hydrochloride, phentolamine mesylate and papaverine hydrochloride in men with moderate to severe erectile dysfunction.

    Science.gov (United States)

    Lammers, P I; Rubio-Aurioles, E; Castell, R; Castaneda, J; Ponce de Leon, R; Hurley, D; Lipezker, M; Loehr, L A; Lowrey, F

    2002-02-01

    Oral therapy has become first line treatment for patients with mild to moderate erectile dysfunction (ED). Studies have shown that sildenafil may not be effective in all patients, and has been associated with a variety of adverse effects and an adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes. The objective was to compare the efficacy and safety of three different oral combinations with the highest dose of sildenafil in men with moderate to severe ED. Randomized, double blind, unblinded active-controlled, Phase II study was carried out at three sites in Mexico. After a 4-week placebo run-in period, patients received all four of the following treatments using a 4-way cross-over design: 40 mg phentolamine (PM) +6 mg apomorphine (Apo); 40 mg PM +150 mg papaverine (Pap); 40 mg PM +6 mg Apo +150 mg Pap (Tricombo); 100 mg sildenafil (SC). With the exception of sildenafil tablets, all study medication was blinded. Moderate to severe ED was defined as a less than 50% vaginal penetration success rate during the placebo run-in period. A total of 44 patients were enrolled, of whom 36 completed all four treatment periods. All treatments produced a significant effect in primary efficacy variable (Sexual Encounter Profile) compared to baseline, however, no statistically significant differences were found between treatments. A significant period effect was observed. Also, the four treatments were found not to differ significantly in five out of six secondary efficacy variables. The lowest incidence of treatment-related adverse events (AE) occurred in the 40 mg PM +6 mg Apo group (9.8%), followed by 100 mg SC (15%), and the other two combinations (16.7 and 17.5%, respectively). Nasocongestion and headache were the most frequently reported AE. An oral combination of vasoactive agents may provide an alternative approach to sildenafil. Based on these results a combination of phentolamine and apomorphine warrants further clinical investigation.

  9. 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

    Background 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. Methods and results 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 AgNO3 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

  10. 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

  11. The comparison of removing plug by ultrasonic wave, chemical deplugging agent and ultrasound-chemical combination deplugging for near-well ultrasonic processing technology.

    Science.gov (United States)

    Wang, Zhenjun; Xu, Yuanming; Bajracharya, Suman

    2015-11-01

    Near-well ultrasonic processing technology is characterized by high adaptability, simple operation, low cost and zero pollution. The main plugs of oil production include paraffin deposition plug, polymer plug, and drilling fluid plug etc. Although some good results have been obtained through laboratory experiments and field tests, systematic and intensive studies are absent for certain major aspects, such as: effects of ultrasonic treatment for different kinds of plugs and whether effect of ultrasound-chemicals combination deplugging is better than that of ultrasonic deplugging. In this paper, the experiments of removing drilling fluid plug, paraffin deposition plug and polymer plug by ultrasonic wave, chemical deplugging agent and ultrasound-chemical combination deplugging respectively are carried out. Results show that the effect of ultrasound-chemical combination deplugging is clearly better than that of using ultrasonic wave and chemical deplugging agent separately, which indicates that ultrasonic deplugging and chemical deplugging can produce synergetic effects. On the one hand, ultrasonic treatment can boost the activity of chemical deplugging agent and turn chemical deplugging into dynamic chemical process, promoting chemical agent reaction speed and enhancing deplugging effect; on the other hand, chemical agent can reduce the adhesion strength of plugs so that ultrasonic deplugging effect can be improved significantly. Experimental results provide important reference for near-well ultrasonic processing technology.

  12. 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

  13. Widening the path and window of opportunity for FDA approval of non-vitamin K oral anticoagulant specific antidotes and reversal agents.

    Science.gov (United States)

    Patel, Sunny; Steen, Dylan

    2016-02-01

    There remains a need for safe, immediately effective, and easy to administer antidotes for patients taking novel oral anticoagulants (NOACs) in the settings of major bleeding, need for emergency surgery, and accidental overdose. We review considerations for the successful safety and effectiveness evaluation of potential antidotes currently under development. These compounds are in expedited regulatory approval programs aimed at accelerating the preclinical and clinical evaluation and approval processes for treatments of serious conditions. We review the features of these expedited programs as well as the FDA's efforts to broadly advance the efficiency of drug development and increase the number of new compounds brought to market. The critical path initiative and regulatory science initiative have resulted in numerous successful programs to address current challenges such as a paucity of validated biomarkers and surrogate endpoints as well as unreliable animal models of toxicity. The FDA has also advocated for increased use of pharmacokinetic/pharmacodynamic modeling and adaptive trial design. These efforts foster collaboration between academia, industry and the public sector across interdisciplinary sciences and may continue to widen the pathway for NOAC-specific reversal agents and other novel compounds.

  14. Determination of designer doping agent--2-ethylamino-1-phenylbutane--in dietary supplements and excretion study following single oral supplement dose.

    Science.gov (United States)

    Wójtowicz, Marzena; Jarek, Anna; Chajewska, Katarzyna; Turek-Lepa, Ewa; Kwiatkowska, Dorota

    2015-11-10

    The quantitative analysis of a new designer doping agent, 2-ethylamino-1-phenylbutane (EAPB) and its metabolite, 2-amino-1-phenylbutane (APB) in urine samples, and the determination of EAPB in dietary supplement samples, have been presented. The main purpose of the present study was to develop simple and reliable gas chromatography-mass spectrometry method (GC-MS) for excretion study following a single oral administration of dietary supplements containing EAPB. Three analytical methods for the determination of EAPB in urine and supplement samples, and APB in urine samples using the GC-MS system, have been validated. The method of the determination of EAPB in supplement samples was applied to analyze seventeen dietary supplements, CRAZE and DETONATE. Two other methods were used to determine the urinary excretion profile of EAPB and APB in the case of three healthy volunteers and, on further investigation, it was applied to the anti-doping control in sport. Quantification was obtained on the basis of the ions at m/z 86, 58 and 169, monitored for EAPB, APB and diphenylamine (used as an internal standard), respectively. The limits of detection and quantification were 2.4 and 7.3μg/g for EAPB in the case of supplement analysis, 2.9 and 8.8ng/mL for EAPB in the case of urine analysis, and 3.2 and 9.7ng/mL for APB. The other validation parameters as linearity, precision and trueness have been also investigated with the acceptable results. The extraction yield of all presented methods was above 69%. EAPB was detected in fourteen analyzed supplements (not included EAPB in their labels) and its content varied between 1.8 and 16.1mg/g. Following oral administration of three supplements with EAPB to one male and two female volunteers, the parent compound of EAPB and its metabolite were monitored and the excretion parameters as the maximum concentration of the analyte in urine (2.2-4.2μg/mL for EAPB; 1.1-5.1μg/mL for APB) and the time for the maximum height of the excretion

  15. Ceftolozane/tazobactam and ceftazidime/avibactam: two novel β-lactam/β-lactamase inhibitor combination agents for the treatment of resistant Gram-negative bacterial infections.

    Science.gov (United States)

    Liscio, Jordan L; Mahoney, Monica V; Hirsch, Elizabeth B

    2015-09-01

    The rise in resistant Gram-negative bacteria is a major concern and has led to difficulty in treating multidrug-resistant (MDR) infections. Two recently approved combination antibiotics, ceftolozane/tazobactam and ceftazidime/avibactam, may be effective in treating these resistant infections. Ceftolozane is a novel cephalosporin that has been developed in combination with tazobactam, a recognised β-lactamase inhibitor (BLI). Avibactam is a novel BLI combined with ceftazidime, a cephalosporin with an established history. Both of these β-lactam/BLI combination agents have been shown to retain in vitro activity against selected resistant Gram-negative pathogens, including Enterobacteriaceae and Pseudomonas aeruginosa; notably, ceftazidime/avibactam has demonstrated consistent activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms. Both agents have been approved for the indications of complicated intra-abdominal infection (with metronidazole) and complicated urinary tract infection, and have ongoing phase 3 trials for the treatment of ventilator-associated and nosocomial pneumonia. This manuscript will review current data available regarding the spectrum of activity and clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents. Both agents appear to be well tolerated and show promise in the treatment of MDR Gram-negative infections.

  16. Agent-Based Control of Distributed Electricity Generation with Micro Combined Heat and Power: Cross-Sectoral Learning for Process and Infrastructure Engineers

    NARCIS (Netherlands)

    Van Dam, K.H.; Houwing, M.; Lukszo, Z.; Bouwmans, I.

    2007-01-01

    For the distributed control of an electricity infrastructure incorporating clusters of residential combined heat and power units (micro-CHP or μCHP) a Multi-Agent System approach is considered. The network formed by households generating electricity with μCHP units and the facilitating energy

  17. Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain

    Science.gov (United States)

    Maia, Hugo; Haddad, Clarice; Casoy, Julio

    2014-01-01

    Endometriosis is a chronic disease in which a persistent state of heightened inflammation is maintained by nuclear factor-kappa B (NF-κB) activation. The progestins present in oral contraceptives are potent inhibitors of NF-κB translocation to cell nuclei, while Pycnogenol® (Pinus pinaster) acts by blocking post-translational events. In this study, the effects of Pycnogenol on pain scores were investigated in patients with endometriosis using oral contraceptives containing either gestodene or drospirenone in extended regimens. Pain scores were determined using a visual analog scale before and after 3 months of treatment. Oral contraceptives, used alone (groups 1 and 3) or in association with Pycnogenol (groups 2 and 4), resulted in significant decreases in pain scores after 3 months of treatment; however, this reduction was significantly greater in the groups using oral contraceptives + Pycnogenol (groups 2 and 4) compared with those using oral contraceptives alone (groups 1 and 3). In the groups using oral contraceptives alone, 50% of patients became pain-free by the end of the third month of treatment. These results suggest that Pycnogenol increases the efficacy of oral contraceptives for the treatment of endometriosis-related pain. PMID:24379702

  18. 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.

  19. 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 unmo