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Sample records for sublingual combination formulation

  1. Formulation and evaluation of sublingual tablets of losartan potassium

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    Nikunj J. Aghera

    2012-05-01

    Full Text Available Objective: Sublingual tablets of Losartan Potassium were prepared to improve its bioavailability, to avoid pre-systemic metabolism in the gastrointestinal tract and hepatic first pass elimination. Methods: The Sublingual tablets were prepared by direct compression procedure using different concentration of Starch 1500 and microcrystalline cellulose. Compatibility studies of drug and polymer were performed by FTIR spectroscopy and DSC. Preformulation property of API was evaluated. Postcompressional parameters such disintegration time, wetting time, water absorption ratio, in vitro drug release and in vivo bioavailability study of optimized formulation were determined. Results: FTIR spectroscopy and DSC study revealed that there was no possible interaction between drug and polymers. The precompression parameters were in acceptable range of pharmacopoeial specification. The disintegration time of optimized formulation (F3 was upto 48 sec. The in vitro release of Losartan Potassium was upto 15 min. The percentage relative bioavailability of Losartan Potassium from optimized sublingual tablets was found to be 144.7 %. Conclusions: Sublingual tablets of Losartan Potassium were successfully prepared with improved bioavailability.

  2. Formulation and Evaluation of New Glimepiride Sublingual Tablets

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    Wafa Al-Madhagi

    2017-01-01

    Full Text Available Oral mucosal delivery of drugs promotes rapid absorption and high bioavailability, with a subsequent immediate onset of pharmacological effect. However, many oral mucosal deliveries are compromised by the possibility of the patient swallowing the active substance before it has been released and absorbed locally into the systemic circulation. The aim of this research was to introduce a new glimepiride formula for sublingual administration and rapid drug absorption that can be used in an emergency. The new sublingual formulation was prepared after five trials to prepare the suitable formulation. Two accepted formulations of the new sublingual product were prepared, but one of them with disintegration time of 1.45 min and searching for preferred formulation, the binder, is changed with Flulac and starch slurry to prepare formula with disintegration time of 21 seconds that supports the aim of research to be used in an emergency. The five formulations were done, after adjusting to the binder as Flulac and aerosil with disintegration time of 21 seconds and accepted hardness as well as the weight variation. The assay of a new product (subglimepiride is 103% which is a promising result, confirming that the formula succeeded. The new product (subglimepiride is accepted in most quality control tests and it is ready for marketing.

  3. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

    OpenAIRE

    Fischer, Andreas; J?nsson, Martin; Hjelmstr?m, Peter

    2013-01-01

    Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv?), using su...

  4. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers.

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    Fischer, Andreas; Jönsson, Martin; Hjelmström, Peter

    2015-01-01

    Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg). Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. A sublingual tablet formulation with an improved acceptability has been successfully developed.

  5. Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration

    NARCIS (Netherlands)

    Srinarong, Parinda; Pham, Bao T; Holen, Maru; van der Plas, Afke; Schellekens, Reinout C A; Hinrichs, Wouter L J; Frijlink, Henderik W

    The aim of this study was to develop a new fast-disintegrating tablet formulation containing 1mg tacrolimus for sublingual application. First, solid dispersions containing tacrolimus (2.5%, 5% and 10% w/w) incorporated in Ac-Di-Sol®and carriers (inulin 1.8kDa and 4kDa, and polyvinylpyrrolidone (PVP)

  6. Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model.

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    Rawas-Qalaji, Mutasem; Rachid, Ousama; Mendez, Belacryst A; Losada, Annette; Simons, F Estelle R; Simons, Keith J

    2015-01-01

    For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model. The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively. Epimean (standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P adrenaline levels). Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings. © 2014 Royal Pharmaceutical Society.

  7. In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

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    Lim SCB

    2013-04-01

    Full Text Available Stephen CB Lim,1,3 Michael J Paech,2 Bruce Sunderland,3 Yandi Liu3 1Pharmacy Department, Armadale Health Service, Armadale, 2School of Medicine and Pharmacology, University of Western Australia, and Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, Subiaco, 3School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia Background: The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods: The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results: In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion: These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. Keywords: absolute bioavailability, fentanyl wafer, in vitro dissolution, in vivo study, pharmacokinetics, sublingual

  8. In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

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    Lim, Stephen CB; Paech, Michael J; Sunderland, Bruce; Liu, Yandi

    2013-01-01

    Background The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. PMID:23596347

  9. Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

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    Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

    2017-01-01

    In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

  10. Fast Dissolving Sublingual Films Containing Sumatriptan Alone and Combined with Methoclopramide: Evaluation in Vitro Drug Release and Mucosal Permeation

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    Maryam Maghsoodi, Mahdieh Rahmani, Hamed Ghavimi, Seyed Hassan Montazam, Saieede Soltani, Mitra Alami, Sara Salatin, Mitra Jelvehgari

    2016-10-01

    Full Text Available ackground: Sumatriptan succinate is a 5-HT1 receptor agonist which is used in the treatment of migraine. It shows low bioavailability (15% due to high hepatic first pass metabolism. The present work intended to formulate mucoadhesive sublingual films of sumatriptan combined with metoclopramide and sumatriptan alone with the objective of improving the therapeutic efficacy, patient compliance, and bioavailability. Methods: The sublingual films were formulated by solvent casting technique using mucoadhesive polymer of hydroxypropyl methylcellulose and propylene glycol as plasticizers. This study was also designed to evaluate the physicochemical and mucoadhesive characteristics of the films. The films were evaluated for their mechanical strength, folding endurance, drug content uniformity, swelling, in vitro residence time, in vitro release, in vitro bioadhesion, and in vivo mucoadhesion. Results: They showed good appearance and elasticity. The best drugs of polymer ratio were S3 (1:2 and SM2 (2.7:1:8. The film of S3 and SM2 showed 10.6 and 11.01 mg weight, 2.2 and 22.5 µm thickness, 300 folding endurance, 55.9 and 100% content uniformity, respectively. The Differential Scanning Calorimetry (DSC showed no stable sample of sumatriptan and metoclopramide in the drug loaded films and revealed amorphous form and transition of hydrate to anhydrous form for metoclopramide. The results showed that the films prepared were fast dissolving. The films (sumatriptan combined with metoclopramide and sumatriptan alone exhibited very good mucoadhesive properties and shorter retention time (15-30 s. Conclusion: The formulations were found to be suitable candidates for the development of sublingual films for therapeutic uses.

  11. Formulation and Characterization of Fast-Dissolving Sublingual Film of Iloperidone Using Box-Behnken Design for Enhancement of Oral Bioavailability.

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    Londhe, Vaishali; Shirsat, Rucha

    2018-02-02

    Iloperidone is a second-generation antipsychotic drug which is used for the treatment of schizophrenia and has very low aqueous solubility and bioavailability. This drug also undergoes first-pass metabolism. The aim of this work is to formulate fast-dissolving sublingual films of iloperidone to improve its bioavailability. Sublingual films were prepared by solvent casting method. Hydroxypropyl methyl cellulose E5, propylene glycol 400, and transcutol HP were optimized using Box-Behnken three-level statistical design on the basis of disintegration time and folding endurance of films. Iloperidone:hydroxypropyl-β-cyclodextrin kneaded complex was used in films instead of plain drug due to its low solubility. Optimized film was further evaluated for drug content, pH, dissolution studies, ex vivo permeation studies, and pharmacokinetic studies in rats. The optimized film disintegrated within 30 s. The in vitro dissolution of the film showed 80.3 ± 3.4% drug dissolved within first 5 min. In ex vivo permeation studies using sublingual tissue, flux achieved within first 15 min by film was around 117.1 ± 0.35 (mcg/cm 2 /h) which was ten times more than that of plain drug. This formulation showed excellent uniformity. AUC and C max of film were significantly higher (p films was 148% when compared to the plain drug. Thus, this study showed optimized fast-dissolving sublingual film to improve permeation and bioavailability of iloperidone. Fast-dissolving films will be customer-friendly approach for geadiatric schizophrenic patients.

  12. Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in African children with malaria.

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    Salman, Sam; Bendel, Daryl; Lee, Toong C; Templeton, David; Davis, Timothy M E

    2015-01-01

    The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in 91 young African children with severe malaria or who could not tolerate oral antimalarial therapy. Each received 3.0 mg/kg of body weight of artemether at 0, 8, 24, 36, 48, and 60 h or until the initiation of oral treatment. Few blood samples were drawn postdose. Plasma artemether and dihydroartemisinin (DHA) levels were measured using liquid chromatography-mass spectrometry, and the data were analyzed using established population compartmental pharmacokinetic models. Parasite clearance was prompt (median parasite clearance time, 24 h), and there were no serious adverse events. Consistent with studies in healthy adults (S. Salman, D. Bendel, T. C. Lee, D. Templeton, and T. M. E. Davis, Antimicrob Agents Chemother 59:3197-3207, 2015, http://dx.doi.org/10.1128/AAC.05013-14), the absorption of sublingual artemether was biphasic, and multiple dosing was associated with the autoinduction of the metabolism of artemether to DHA (which itself has potent antimalarial activity). In contrast to studies using healthy volunteers, pharmacokinetic modeling indicated that the first absorption phase did not avoid first-pass metabolism, suggesting that the drug is transferred to the upper intestine through postdose fluid/food intake. Simulations using the present data and those from an earlier study in older Melanesian children with uncomplicated malaria treated with artemether-lumefantrine tablets suggested that the bioavailability of sublingual artemether was at least equivalent to that after conventional oral artemether-lumefantrine (median [interquartile range] areas under the concentration-time curve for artemether, 3,403 [2,471 to 4,771] versus 3,063 [2,358 to 4,514] μg · h/liter, respectively; and for DHA, 2,958 [2,146 to 4,278] versus 2,839 [1,812 to 3,488] μg · h/liter, respectively; P ≥ 0.42). These findings suggest that sublingual artemether could be used as prereferral treatment for sick

  13. Assessment of the ventilation function and serum biochemical indexes after sublingual dermatophagoides farinae drops combined with loratadine treatment of children with asthma and allergic rhinitis

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    Ruo-Qing Qiu

    2017-06-01

    Full Text Available Objective: To study the ventilation function after sublingual dermatophagoides farinae drops combined with loratadine treatment of children with asthma and allergic rhinitis and the influence on serum biochemical indexes. Methods: A total of 40 children with asthma and allergic rhinitis treated in our hospital between September 2013 and March 2015 were collected and divided into the control group (n=22 who accepted loratadine therapy alone and the observation group (n=18 who accepted sublingual dermatophagoides farinae drops combined with loratadine therapy after the treatment was reviewed. Before treatment and after 6 months and 1 year of treatment, spirometer was used to test ventilation function indexes; ELISA method was used to determine the contents of inflammatory mediators; RIA method was used to determine the contents of airway remodeling indicators. Results: Before treatment, differences in ventilation function index levels as well as inflammatory mediator and airway remodeling index contents were not statistically significant between two groups of children. After 6 months and 1 year of treatment, FEV1, FVC and PEF levels of observation group were higher than those of control group; serum IL-2 content was higher than that of control group while IL-5, IL-17 and IL-33 contents were lower than those of control group; serum PDGFBB, TGF-β1 and NF-κB contents were lower than those of control group. Conclusion: Sublingual dermatophagoides farinae drops combined with loratadine therapy can optimize the ventilation function, reduce the systemic inflammatory response and inhibit airway remodeling in children with asthma and allergic rhinitis.

  14. Budgetary impact of the utilization of buprenorphine/naloxone sublingual film and tablet for Medicaid in the United States.

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    Asche, Carl V; Clay, Emilie; Kharitonova, Elizaveta; Zah, Vladimir; Ruby, Jane; Aballéa, Samuel

    2015-01-01

    The buprenorphine/naloxone combination for the treatment of opioid dependence is available in a film or tablet formulation. Recent retrospective studies demonstrated that treatment with the sublingual film formulation is associated with improved treatment retention and lower healthcare costs. In March 2013, generic buprenorphine/naloxone tablets were approved in the US. A budget impact model was built to compare healthcare expenditures for different market shares of sublingual film and tablet. A Markov model was developed to track a cohort of opioid dependent patients treated with sublingual film or tablet through the following treatment phases: initiation, maintenance, discontinuation, off-treatment and reinitiation. Transition probabilities and costs for each phase were estimated from the MarketScan Medicaid database for the period between 1 March 2010 and 30 June 2012. The total expenditure for the plan and expenditure per plan member per month were predicted over 5 years. Two market share scenarios were considered: 1) sublingual film is progressively replaced by generic tablet (current situation) and 2) the sublingual film holds a market share of 100%. Predicted total costs over 5 years were $6400 million when the sublingual film holds a market share of 100% (as per Scenario 2) which is lower than when sublingual film is progressively replaced by generic tablet (current situation as per Scenario 1) by $64 million. These savings were mostly driven by inpatient care ($56 million saved over 5 years), followed by emergency room care ($27 million) and pharmaceutical costs ($24 million). Costs of outpatient care attenuated the difference as they were predicted to be higher by $44 million in Scenario 2. The reduction in total cost per member per month reached $0.027 in the fifth year. Results were most sensitive to price rebates and to the probability of non-psychiatric hospitalization. While using the sublingual film formulation for more patients treated with

  15. Fentanyl Sublingual Spray

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    Fentanyl sublingual spray is used to treat breakthrough pain (sudden episodes of pain that occur despite round ... effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic ( ...

  16. A comparison of the effects of morphine and sublingual desmopressin combination therapy with morphine alone in treatment of renal colic: a controlled clinical trial.

    Science.gov (United States)

    Keshvari Shirvani, Maliheh; Darabi Mahboub, Mohammadreza; Ghazi, Mahdi; Delijani, Alireza

    2015-02-22

    To compare the therapeutic efficacy of combined desmopressin and morphine with morphine and placebo on acute renal colic. In a single blind case-control clinical trial 81 consecutive patients, 54 males and 27 females with the mean age of 30.12 ± 9.88 years, presenting with acute renal colic to the urology emergency unit were studied. The patients were randomly assigned into two groups. The 40 cases were treated with 0.1 mg/kg IM morphine and 60 μg of sublingual desmopressin melt; whereas the 41 controls received the same dose of morphine beside a placebo. There were no significant statistical differences regarding the mean age, gender, stone size, location and affected side between the two groups. Our results showed a significantly higher acuity of pain in the study group in comparison to the controls at 10, 20 and 30 minutes of receiving the medication (P = .06, .017 and P = .008, respectively). No superiority was found in adding desmopressin to morphine compared to the traditional treatments (opioids only) in relieving the pain of acute renal colic cases.

  17. A pragmatic approach to the analysis of a combination formulation

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    Noshin Mubtasim

    2016-11-01

    The proposed combination formulation has shown compatibility with the chosen excipients, verified through FT-IR study. A novel gradient RP-HPLC method was developed and validated according to the ICH guideline which was found to be suitable for the simultaneous estimation of rosuvastatin calcium and amlodipine besylate from the formulation. The retention time of 2.7 and 6.08 min allows the analysis of large amount of samples with less mobile phase which makes the method economic. The dissolution profiles of both the drugs in different dissolution medium were encouraging which makes the combination formulation of rosuvastatin calcium and amlodipine besylate superior and effective in achieving patient compliance.

  18. Sublingual allergen immunotherapy

    DEFF Research Database (Denmark)

    Calderón, M A; Simons, F E R; Malling, Hans-Jørgen

    2012-01-01

    -presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast......To cite this article: Calderón MA, Simons FER, Malling H-J, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy 2012; 67: 302-311. ABSTRACT: Allergen immunotherapy reorients inappropriate immune responses...... in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen...

  19. Sublingual vein parameters, AFP, AFP-L3, and GP73 in patients with hepatocellular carcinoma.

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    Zhao, J; Guo, L-Y; Yang, J-M; Jia, J-W

    2015-06-26

    This study evaluated the diagnostic value of alpha-fetoprotein (AFP), AFP heterogeneity 3 (AFP-L3), Golgi protein 73 (GP73), and sublingual vein parameters in hepatocellular carcinoma (HCC). Levels of serum AFP, AFP-L3, GP73, and sublingual vein scores were measured in 34 patients with chronic hepatitis, 65 patients with post-hepatitis B cirrhosis, 71 patients with HCC, and 6 healthy controls. Logistic regression analysis was used to explore potential correlations. Sublingual vein grades in patients with HCC were higher than those in the other three groups; sublingual vein scores were also different between groups; combined diagnosis using AFP, GP73, and sublingual vein grade was superior to the individual parameters alone or when only two were used in different combinations. Thus, sublingual vein grade can be considered as an independent risk factor for diagnosis of HCC. Furthermore, combined detection with AFP, GP73, and sublingual vein grade is simple, inexpensive, and effective. It may therefore be suitable for screening high-risk populations for early diagnosis of HCC.

  20. Formulation And Evaluation of a Combined Chloroquine Phosphate ...

    African Journals Online (AJOL)

    B2) were separately formulated with maize starch and lactose with polyvinylpyrrolidone (10% w/v) as binder. B1 was coated with 5% w/v ethylcellulose to varying degrees by increasing the spray time of the coating solution by 2 minutes ...

  1. The cultural formulation: A model to combine nosology and patients' life context in psychiatric diagnostic practice.

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    Bäärnhielm, Sofie; Scarpinati Rosso, Marco

    2009-09-01

    This article discusses the experience of adapting and applying the Outline for a Cultural Formulation in DSM-IV to the Swedish context. Findings from a research project on the Cultural Formulation highlight the value of combining psychiatric nosological categorization with an understanding of patients' cultural life context in order to increase the validity of categorization and to formulate individualized treatment plans. In clinical care practitioners need models and tools that help them take into account patients' cultural backgrounds, needs, and resources in psychiatric diagnostic practice. We present a summary of a Swedish manual for conducting a Cultural Formulation interview. The need for further development of the Cultural Formulation is also discussed.

  2. Tumors of the sublingual gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; Bjørndal, K; Agander, T K

    2016-01-01

    Tumors of the salivary glands are a heterogeneous group of diseases most often originating in the major salivary glands. Only a minor proportion of mainly malignant tumors arise in the sublingual gland. Due to the rarity of sublingual gland tumors (SGTs), little is known about the clinicopathologic...... characteristics, prognostic factors, and clinical course. We present a large national series of histopathologically revised SGTs from the past 35 years in Denmark with clinicopathologic correlation. Twenty nine cases were identified, of which 96.6 % were malignant and 16/28 (57.1 %) were adenoid cystic carcinomas...... (ACC). Patient demography was similar to salivary gland tumors in other locations. All fine needle aspiration cytologies (FNACs) interpreted as benign were from ACCs. Metastatic disease was found in 12.5 % of ACCs at diagnosis with one third of all ACC patients having metastases at the end of follow...

  3. Development of a new formulation combining calcipotriol and betamethasone dipropionate in an ointment vehicle

    DEFF Research Database (Denmark)

    Simonsen, Lene; Høy, Gert; Didriksen, Erik

    2004-01-01

    was to develop a formulation which combines calcipotriol and betamethasone dipropionate in a single vehicle hereby achieving optimal delivery of both substances into the skin. As the two substances are incompatible in aqueous and alcoholic medias, different non-aqueous formulations were prepared. Skin permeation...

  4. Formule.

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    Le Comité de Rédaction d' EspacesTemps.net

    2004-09-01

    Full Text Available Vous découvrez aujourd’hui la nouvelle formule d’EspacesTemps. net. Ce basculement repose sur des changements techniques d’une certaine ampleur et nous vous demandons d’être indulgents si quelques imperfections subsistent dans les prochains jours. Il s’agit d’abord de la substitution du dispositif de mise en ligne : à partir de maintenant, nous utilisons le logiciel Lodel. Dans l’esprit de l’association Revues.org, à laquelle EspacesTemps adhère, l’unification du ...

  5. Clinical Applications of Sublingual Immunotherapy.

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    Edwards, Thomas S; Wise, Sarah K

    2017-12-01

    Sublingual immunotherapy (SLIT) is effective for the treatment of allergic rhinitis and allergic asthma in adults and children. In a limited number of studies, SLIT efficacy has been demonstrated for the treatment of food allergy. SLIT has a higher safety profile versus subcutaneous immunotherapy, although some systemic reactions have been reported. Appropriate patient selection, meticulous patient education, and routine follow-up are key for the safe and effective administration of SLIT. With organization and attention to detail, adding SLIT to one's practice can provide a highly valued patient service. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Sublingual desmopressin is efficient and safe in the therapy of lithiasic renal colic.

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    Pricop, Catalin; Branisteanu, Dumitru D; Orsolya, Martha; Puia, Dragos; Matei, Anca; Checherita, Ionel Alexandru

    2016-02-01

    To evaluate the effects of newer sublingual desmopressin administration in lithiasic renal colic, alone or combined with a nonsteroidal anti-inflammatory drug (NSAID). Prospective single-blind study including an initial number of 249 patients with lithiasic renal colic was randomized as follows: group NSAID (71 patients) received ketorolac tromethamine (ketorolac) 30 mg im and sublingual placebo (vitamin C), groups D1 and D2 (57 and 62 patients) received sublingual desmopressin (Minirin Melt), 60 and 120 μg, respectively, whereas group C (59 patients) received a combination of 30 mg im ketorolac and 60 μg sublingual desmopressin. Pain intensity was assessed using the visual analogue scale before and thirty minutes after drug administration. Patients experiencing pain aggravation were rescued and excluded from the study. Dropout incidence was higher in the NSAID group than in the groups treated with desmopressin in monotherapy or combined with ketorolac (p desmopressin and ketorolac. The higher dose of desmopressin and the combination therapy decreased pain intensity with 56 and 59%, respectively, significantly more than the 47% decrease obtained with ketorolac alone (p desmopressin is at least as potent as NSAID in the treatment of lithiasic renal colic. The combination of sublingual desmopressin and NSAID has additive analgesic effects.

  7. Benefits of Combinations of Vitamin A, C and E Derivatives in the Stability of Cosmetic Formulations

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    Patrícia Maria Berardo Gonçalves Maia Campos

    2012-02-01

    Full Text Available Chemically stable ester derivatives of vitamins A, C and E have become a focus of interest for their role in the satisfactory results in skin aging treatments. Accordingly, the aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies of physical stability, a Brookfield rheometer was used to determine rheological behavior of formulations containing the vitamins. Chemical stability was determined by HPLC on a Shimadzu system with UV detection. Results showed that formulations had pseudoplastic behavior and that vitamins did not alter their apparent viscosity and thixotropy. In the chemical stability studies, first-order reaction equations were used for determinations of the shelf-life of vitamins derivatives considering a remaining concentration of 85%. Combined vitamins in a single formulation had a slightly lower degradation rate as compared to different preparations containing only one of the vitamins. Considering that many cosmetic formulations contain vitamin combinations it is suggested that the present study may contribute to the development of more stable formulations containing liposoluble vitamins.

  8. Benefits of combinations of vitamin A, C and E derivatives in the stability of cosmetic formulations.

    Science.gov (United States)

    Gianeti, Mirela Donato; Gaspar, Lorena Rigo; Camargo, Flávio Bueno de; Campos, Patrícia Maria Berardo Gonçalves Maia

    2012-02-22

    Chemically stable ester derivatives of vitamins A, C and E have become a focus of interest for their role in the satisfactory results in skin aging treatments. Accordingly, the aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies of physical stability, a Brookfield rheometer was used to determine rheological behavior of formulations containing the vitamins. Chemical stability was determined by HPLC on a Shimadzu system with UV detection. Results showed that formulations had pseudoplastic behavior and that vitamins did not alter their apparent viscosity and thixotropy. In the chemical stability studies, first-order reaction equations were used for determinations of the shelf-life of vitamins derivatives considering a remaining concentration of 85%. Combined vitamins in a single formulation had a slightly lower degradation rate as compared to different preparations containing only one of the vitamins. Considering that many cosmetic formulations contain vitamin combinations it is suggested that the present study may contribute to the development of more stable formulations containing liposoluble vitamins.

  9. New developments in the management of opioid dependence: focus on sublingual buprenorphine–naloxone

    Directory of Open Access Journals (Sweden)

    Soyka M

    2015-01-01

    Full Text Available Michael Soyka1,21Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany; 2Private Hospital Meiringen, Meiringen, SwitzerlandAbstract: Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine–naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed.Keywords: buprenorphine, methadone, naloxone, opioids, opioid dependence, therapy

  10. Intranasal and sublingual delivery of inactivated polio vaccine.

    Science.gov (United States)

    Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

    2017-05-09

    Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

  11. Sublingual immunotherapy: World Allergy Organization position paper 2013 update

    NARCIS (Netherlands)

    G.W. Canonica (Giorgio Walter); L. Cox (Linda); R. Pawankar (Ruby); C.E. Baena-Cagnani (Carlos); M.S. Blaiss (Michael); S. Bonini (Sergio); J. Bousquet (Jean); M. Calderon (Moises); E. Compalati (Enrico); S.R. Durham (Stephen); R. Gerth van Wijk (Roy); D. Larenas-Linnemann (Désirée); H. Nelson (Harold); G. Passalacqua (Giovanni); O. Pfaar (Oliver); K. Rosario (Karyna); D. Ryan (Dermot); L. Rosenwasser (Lanny); P. Schmid-Grendelmeier (Peter); G.E. Senna (Gianenrico); E. Valovirta (Erkka); H.P. van Bever (Hugo); P. Vichyanond (Pakit); U. Wahn (Ulrich); O.M. Yusuf (Osman)

    2014-01-01

    textabstractWe have prepared this document, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update", according to the evidence-based criteria, revising and updating chapters of the originally published paper, "Sublingual Immunotherapy: World Allergy Organization Position

  12. Sublingual vs. Oral Captopril in Hypertensive Crisis.

    Science.gov (United States)

    Kaya, Adnan; Tatlisu, Mustafa Adem; Kaplan Kaya, Tugba; Yildirimturk, Ozlem; Gungor, Baris; Karatas, Baran; Yazici, Selcuk; Keskin, Muhammed; Avsar, Sahin; Murat, Ahmet

    2016-01-01

    There are confusing data in literature regarding oral and sublingual captopril effects over blood pressure (BP) decrease. In our study we compared oral and sublingual captopril effectiveness over BP decrease in patients admitted to our Emergency Department with hypertensive urgency. Our study was conducted from January 2012 to January 2013 in patients with hypertensive urgency. In this cross-sectional study after two initial BP measurements, patients were identified as eligible for the study. An initial electrocardiogram was obtained and blood samples were drawn. A total of 212 patients were accepted as eligible for the study, and 25 mg of captopril was randomly given orally or sublingually; BP was measured at 10, 30, and 60 min. We selected the patients to the groups consecutively. A 25% reduction of initial BP 1 h after initiation of the treatment was accepted as an accomplishment. A second 25 mg of captopril was given if the target of 25% reduction of BP was not reached after the first tablet. Intravenous drugs were administered to the patients resistant to the captopril and these patients were excluded from the study. The 10-min systolic BP (SBP), diastolic BP, and mean BP (MBP) decrease was more prominent in the sublingual captopril group (p  0.05). In our study, sublingual captopril was found to decrease BP more efficiently in the first 30 min, but this difference equalized at 60 min. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans.

    Science.gov (United States)

    Solomon, Keith R; Wilks, Martin F; Bachman, Ammie; Boobis, Alan; Moretto, Angelo; Pastoor, Timothy P; Phillips, Richard; Embry, Michelle R

    2016-11-01

    When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs.

  14. Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers.

    Science.gov (United States)

    Kaialy, Waseem; Emami, Parastou; Asare-Addo, Kofi; Shojaee, Saeed; Nokhodchi, Ali

    2014-05-01

    Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12 h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12 h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.

  15. Sublingual immunotherapy in children with allergic rhinitis : quality of systematic reviews

    NARCIS (Netherlands)

    de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roeder, Esther; van Wijk, Roy G.; van der Wouden, Johannes C.

    Systematic reviews have gained popularity as a way to combine the increasing amount of research information. This study assessed the quality of systematic reviews and meta-analyses of sublingual immunotherapy (SLIT) for allergic rhinitis in children, published since 2000. Eligible reviews were

  16. Fast-disintegrating sublingual tablets: Effect of epinephrine load on tablet characteristics

    OpenAIRE

    Rawas-Qalaji, Mutasem M.; Estelle, F.; Simons, R.; Simons, Keith J.

    2006-01-01

    The aim of this study was to evaluate the effect of increasing epinephrine load on the characteristics of fast-disintegrating sublingual tablets for the potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C, and D, containing 0%, 6%, 12%, and 24% of epinephrine bitartrate, respectively, and microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9∶1), were prepared by direct compression, at a range of compression forces. Tablet weight variation, content u...

  17. Tinnitus after administration of sublingual immunotherapy

    DEFF Research Database (Denmark)

    Juel, Jacob

    2017-01-01

    , for example, itching, swelling, irritation, ulceration of the oropharynx and nausea, abdominal pain, diarrhoea, and vomiting. More severe side effects are dominated by systemic and respiratory tract manifestations. RESULTS: In this clinical case, the author reports a right-sided transient tinnitus lasting...... for 48 h after administration of sublingual immunotherapy for house dust mite in allergic rhinitis. CONCLUSIONS: This case provide important insights for clinical practice, as tinnitus has not been previously reported as a side effect of sublingual immunotherapy with house dust mite allergens....

  18. Aerodynamic deposition of combination dry powder inhaler formulations in vitro: a comparison of three impactors.

    Science.gov (United States)

    Taki, Mohammed; Marriott, Christopher; Zeng, Xian-Ming; Martin, Gary P

    2010-03-30

    Inertial impaction is generally regarded as the 'gold standard' for the in vitro assessment of aerodynamic deposition of inhaled formulations. Despite the availability of several impactors, few studies have compared measurements of aerodynamic deposition using multiple impactors and none employed a combination formulation. The aerodynamic deposition of the combination dry powder inhaler (DPI) Seretide Accuhaler, which contains salmeterol xinafoate (SX) and fluticasone propionate (FP), was assessed using the Andersen cascade impactor (ACI), multi-stage liquid impinger (MSLI) and next generation impactor (NGI) and the results were compared. Two Seretide products were tested at flow rates of 30 and QLmin(-1), the latter corresponding to a pressure drop of 4kPa across the device. Significant differences in the particle size distributions were observed when the same formulation was tested using various impactors. The ACI was found to be less suitable for DPI testing at flow rates considerably higher than 28.3Lmin(-1) due to the significant overlap in the cut-off curves of the pre-separator and stage 0. This was not the case with the MSLI but the data derived were limited by the relatively small number of stages. Deposition data determined by the three impactors were significantly different. The NGI produced good resolution and minimal inter-stage overlap and was regarded as the impactor of choice for DPI testing. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  19. Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants.

    Directory of Open Access Journals (Sweden)

    Rachel P J Lai

    Full Text Available Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA, are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (p<0.05. Sequential prime-boost immunizations with different adjuvants did not offer improvements over the use of FCA/FIA or MF59. Remarkably however, the concurrent use of the combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (p<0.05. This combination was not associated with any obvious local or systemic adverse effects. Antibody competition indicated that the majority of the neutralizing activities were directed to the CD4 binding site (CD4bs. Increased antibody titers to the gp41 membrane proximal external region (MPER and gp120 V3 were detected when the more potent adjuvants were used. These data reveal that the combination of Carbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes.

  20. Investigating the potential benefits of a new artificial tear formulation combining two polymers

    Directory of Open Access Journals (Sweden)

    Simmons PA

    2017-09-01

    Full Text Available Peter A Simmons, Joseph G Vehige Allergan plc, Irvine, CA, USA Purpose: Artificial tear formulations typically contain a water-soluble polymer to enhance residence time, moisture retention, and binding to the mucin coat of the ocular surface, which facilitate corneal healing. This study investigated the potential advantages of combining carboxymethylcellulose (CMC and hyaluronic acid (HA polymers in a single formulation. Materials and methods: Individual CMC and HA solutions were prepared and tested for bulk viscosity in comparison to a solution that combined CMC and HA. Rheometry determined the differences between solutions at increasing shear rates, simulating eye movement and blinking. Results: The bulk viscosity of the individual 0.5% CMC and 0.1% HA solutions was 2.5 and 5.7 cP, respectively. The viscosity of the combined solution (13.1 cP was 60% higher than predicted by additive effects. Rheometry revealed shear rates between 10/second (open eye and 10,000/second (blinking eye. At these rates, viscosity ranged from 2.7 to 3.5 cP for 0.5% CMC, 2.8 to 6.8 cP for 0.1% HA, and 5.2 to 15.3 cP for the 0.5% CMC–0.1% HA combination. Low-shear viscosity of the CMC–HA combination increased 48% over the sum of the individual solutions, but high-shear viscosity remained virtually unchanged. Data from CMC and HA solutions at higher concentrations were consistent with these results. Conclusion: Combining CMC and HA polymers produced a synergistic increase in low-shear viscosity (which cannot be fully explained by simple molecular entanglement, while the high-shear viscoelasticity of the combined solution remained unaffected. These data suggest that CMC–HA combinations have properties that may be used to formulate artificial tears that optimize ocular retention (through higher low-shear viscosity, while minimizing blur and stickiness during blinking (through lower high-shear viscosity. Keywords: artificial tear, eyedrop, dry eye

  1. Development and characterization of gastroretentive sustained-release formulation by combination of swelling and mucoadhesive approach: a mechanistic study.

    Science.gov (United States)

    Sankar, R; Jain, Subheet Kumar

    2013-01-01

    Acyclovir has pharmacokinetic limitations, including poor oral bioavailability of 15%-30%, high variability, and short elimination half-life of 2.3 hours. These limitations necessitate frequent administration of acyclovir, up to five times daily, leading to poor patient compliance, which in turn leads to a reduction in therapeutic efficacy and development of resistance. A gastroretentive sustained-release (GR) formulation of acyclovir, based on a combination of swelling and mucoadhesive mechanisms, has been developed. Composition has been optimized after evaluation of different polymers, carbomer, polyethylene oxide, and sodium alginate alone and/or in combination. GR formulations were characterized for in-process quality-control tests, drug release and release rate kinetics, similarity factor analysis, swelling index, and matrix erosion. A formulation containing a combination of carbomer and polyethylene oxide had the highest similarity of drug release compared with a target drug-release profile obtained by pharmacokinetic simulations. The measurement of mucoadhesive strength, carried out with a texture analyzer, showed that the mucoadhesive strength of the GR formulation was significantly higher than that of the immediate-release (IR) tablet. The optimized GR formulation was found to be retained in the upper part of the gastrointestinal tract for 480 minutes; the IR tablet was retained for only 90 minutes as measured using a gastrointestinal retention study in albino rabbits. The GR formulation was also found to maintain more sustained plasma concentrations than the IR tablet. Mean residence time of the GR formulation was 7 hours versus 3.3 hours for the IR formulation. The relative bioavailability of the GR formulation was 261% of the IR formulation. The GR formulation of acyclovir, based on swelling and mucoadhesive mechanisms, has prolonged retention in the upper gastrointestinal tract, sustained in vitro drug release, prolonged in vivo absorption, and better

  2. Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

    Directory of Open Access Journals (Sweden)

    Allam A

    2016-08-01

    Full Text Available Ayat Allam, Gihan Fetih Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt Abstract: The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes, while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration following sublingual administration was found to be significantly higher (91.06%±13.28%, as compared with that after oral tablet administration (39.37%±11.4%. These results indicate that the fast dissolving niosomal film could be a promising delivery system to

  3. Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund's Adjuvants

    Science.gov (United States)

    Lai, Rachel P. J.; Seaman, Michael S.; Tonks, Paul; Wegmann, Frank; Seilly, David J.; Frost, Simon D. W.; LaBranche, Celia C.; Montefiori, David C.; Dey, Antu K.; Srivastava, Indresh K.; Sattentau, Quentin; Barnett, Susan W.; Heeney, Jonathan L.

    2012-01-01

    Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA), are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs) was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (pCarbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (pCarbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes. PMID:22509385

  4. Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants.

    Science.gov (United States)

    Lai, Rachel P J; Seaman, Michael S; Tonks, Paul; Wegmann, Frank; Seilly, David J; Frost, Simon D W; LaBranche, Celia C; Montefiori, David C; Dey, Antu K; Srivastava, Indresh K; Sattentau, Quentin; Barnett, Susan W; Heeney, Jonathan L

    2012-01-01

    Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA), are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs) was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (pCarbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (pCarbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes.

  5. Tinnitus after administration of sublingual immunotherapy

    DEFF Research Database (Denmark)

    Juel, Jacob

    2017-01-01

    BACKGROUND/OBJECTIVES: Sublingual immunotherapy was first described in 1986. Since then, its use has been increased as an alternative to subcutaneously administered immunotherapy in the treatment of allergic rhinitis. The most common side effects are of oropharyngeal and gastrointestinal in natur...

  6. Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers

    Science.gov (United States)

    Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

    2014-01-01

    Aims The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Methods Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Results Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Conclusions Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. PMID:24809233

  7. Dental Composite Formulation Design with Bioactivity on Protein Adsorption Combined with Crack-Healing Capability

    Directory of Open Access Journals (Sweden)

    Chen Chen

    2017-09-01

    Full Text Available Fracture and secondary caries are the primary reasons for the failure of dental restorations. To face this omnipresent problem, we report the formulation design and synthesis of a protein-resistant dental composite composed of 2-methacryloyloxyethyl phosphorylcholine (MPC that also can self-repair damage and recover the load-bearing capability via microencapsulated triethylene glycol dimethacrylate (TEGDMA and N,N-dihydroxy ethyl-p-toluidine (DHEPT. The bioactivity of the resulting MPC-microencapsulated TEGDMA-DHEPT was evaluated on protein adsorption through early bacterial attachment. Its mechanical properties were also investigated, including self-healing assessment. Microcapsules of poly (urea-formaldehyde (PUF were synthesized by incorporating a TEGDMA-DHEPT healing liquid. A set of composites that contained 7.5% of MPC, 10% of microcapsules, and without MPC/microcapsules were also prepared as controls. The two distinct characteristics of strong protein repellency and load-bearing recovery were achieved by the combined strategies. The novel dual composite with a combination of protein-repellent MPC and PUF microcapsules for restoring microcracks is a promising strategy for dental restorations to address the two main challenges of fracture and secondary caries. The new dual composite formulation design has the potential to improve the longevity of dental restorations significantly.

  8. Fast-Acting Sublingual Zolpidem for Middle-of-the-Night Wakefulness

    Directory of Open Access Journals (Sweden)

    Joseph V. Pergolizzi

    2014-01-01

    Full Text Available Sleep disorders (somnipathies are conditions characterized by disruptions of sleep quality or of sleep pattern. They can involve difficulty falling asleep (prolonged sleep onset latency, difficulty staying asleep (disturbance of sleep maintenance, sleep of poor quality (unrefreshing, or combinations of these and can lead to poor health and quality of life problems. A subtype of sleep-maintenance insomnia is middle-of-the-night wakefulness, a relatively common occurrence. Zolpidem, a nonbenzodiazepine benzodiazepine receptor agonist, allosterically modulates an ion channel and increases the influx of Cl−, thereby dampening the effect of excitatory (sleep disrupting input. Recently, product label changes to some zolpidem containing products have been implemented by the FDA in order to reduce the risk associated with their morning after residual side effects. A new formulation of zolpidem tartrate (Intermezzo sublingual tablet, an approved product indicated exclusively for the treatment of middle-of-the-night wakefulness and difficulty returning to sleep, did not have its label changed. We present a short summary of its basic science and clinical attributes in light of the recent regulatory changes for zolpidem products.

  9. Sublingual Immunotherapy for Allergic Fungal Sinusitis.

    Science.gov (United States)

    Melzer, Jonathan M; Driskill, Brent R; Clenney, Timothy L; Gessler, Eric M

    2015-10-01

    Allergic fungal sinusitis (AFS) is a condition that has an allergic basis caused by exposure to fungi in the sinonasal tract leading to chronic inflammation. Despite standard treatment modalities, which typically include surgery and medical management of allergies, patients still have a high rate of recurrence. Subcutaneous immunotherapy (SCIT) has been used as adjuvant treatment for AFS. Evidence exists to support the use of sublingual immunotherapy (SLIT) as a safe and efficacious method of treating allergies, but no studies have assessed the utility of SLIT in the management of allergic fungal sinusitis. A record review of cases of AFS that are currently or previously treated with sublingual immunotherapy from 2007 to 2011 was performed. Parameters of interest included serum IgE levels, changes in symptoms, Lund-McKay scores, decreased sensitization to fungal allergens associated with AFS, and serum IgE levels. Ten patients with diagnosed AFS were treated with SLIT. No adverse effects related to the use of SLIT therapy were identified. Decreases in subjective complaints, exam findings, Lund-McKay scores, and serum IgE levels were observed. Thus, sublingual immunotherapy appears to be a safe adjunct to the management of AFS that may improve patient outcomes. © The Author(s) 2015.

  10. Development and characterization of gastroretentive sustained-release formulation by combination of swelling and mucoadhesive approach: a mechanistic study

    Directory of Open Access Journals (Sweden)

    Sankar R

    2013-12-01

    Full Text Available R Sankar,1 Subheet Kumar Jain1,2 1Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India; 2Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India Background: Acyclovir has pharmacokinetic limitations, including poor oral bioavailability of 15%–30%, high variability, and short elimination half-life of 2.3 hours. These limitations necessitate frequent administration of acyclovir, up to five times daily, leading to poor patient compliance, which in turn leads to a reduction in therapeutic efficacy and development of resistance. Methods: A gastroretentive sustained-release (GR formulation of acyclovir, based on a combination of swelling and mucoadhesive mechanisms, has been developed. Composition has been optimized after evaluation of different polymers, carbomer, polyethylene oxide, and sodium alginate alone and/or in combination. GR formulations were characterized for in-process quality-control tests, drug release and release rate kinetics, similarity factor analysis, swelling index, and matrix erosion. Results: A formulation containing a combination of carbomer and polyethylene oxide had the highest similarity of drug release compared with a target drug-release profile obtained by pharmacokinetic simulations. The measurement of mucoadhesive strength, carried out with a texture analyzer, showed that the mucoadhesive strength of the GR formulation was significantly higher than that of the immediate-release (IR tablet. The optimized GR formulation was found to be retained in the upper part of the gastrointestinal tract for 480 minutes; the IR tablet was retained for only 90 minutes as measured using a gastrointestinal retention study in albino rabbits. The GR formulation was also found to maintain more sustained plasma concentrations than the IR tablet. Mean residence time of the GR formulation was 7 hours versus 3.3 hours for the IR formulation. The relative

  11. Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design.

    Science.gov (United States)

    Isailović, Tanja; Ðorđević, Sanela; Marković, Bojan; Ranđelović, Danijela; Cekić, Nebojša; Lukić, Milica; Pantelić, Ivana; Daniels, Rolf; Savić, Snežana

    2016-01-01

    We aimed to develop lecithin-based nanoemulsions intended for effective aceclofenac (ACF) skin delivery utilizing sucrose esters [sucrose palmitate (SP) and sucrose stearate (SS)] as additional stabilizers and penetration enhancers. To find the suitable surfactant mixtures and levels of process variables (homogenization pressure and number of cycles - high pressure homogenization manufacturing method) that result in drug-loaded nanoemulsions with minimal droplet size and narrow size distribution, a combined mixture-process experimental design was employed. Based on optimization data, selected nanoemulsions were evaluated regarding morphology, surface charge, drug-excipient interactions, physical stability, and in vivo skin performances (skin penetration and irritation potential). The predicted physicochemical properties and storage stability were proved satisfying for ACF-loaded nanoemulsions containing 2% of SP in the blend with 0%-1% of SS and 1%-2% of egg lecithin (produced at 50°C/20 cycles/800 bar). Additionally, the in vivo tape stripping demonstrated superior ACF skin absorption from these nanoemulsions, particularly from those containing 2% of SP, 0.5% of SS, and 1.5% of egg lecithin, when comparing with the sample costabilized by conventional surfactant - polysorbate 80. In summary, the combined mixture-process experimental design was shown as a feasible tool for formulation development of multisurfactant-based nanosized delivery systems with potentially improved overall product performances.

  12. [Formulation of combined predictive indicators using logistic regression model in predicting sepsis and prognosis].

    Science.gov (United States)

    Duan, Liwei; Zhang, Sheng; Lin, Zhaofen

    2017-02-01

    To explore the method and performance of using multiple indices to diagnose sepsis and to predict the prognosis of severe ill patients. Critically ill patients at first admission to intensive care unit (ICU) of Changzheng Hospital, Second Military Medical University, from January 2014 to September 2015 were enrolled if the following conditions were satisfied: (1) patients were 18-75 years old; (2) the length of ICU stay was more than 24 hours; (3) All records of the patients were available. Data of the patients was collected by searching the electronic medical record system. Logistic regression model was formulated to create the new combined predictive indicator and the receiver operating characteristic (ROC) curve for the new predictive indicator was built. The area under the ROC curve (AUC) for both the new indicator and original ones were compared. The optimal cut-off point was obtained where the Youden index reached the maximum value. Diagnostic parameters such as sensitivity, specificity and predictive accuracy were also calculated for comparison. Finally, individual values were substituted into the equation to test the performance in predicting clinical outcomes. A total of 362 patients (218 males and 144 females) were enrolled in our study and 66 patients died. The average age was (48.3±19.3) years old. (1) For the predictive model only containing categorical covariants [including procalcitonin (PCT), lipopolysaccharide (LPS), infection, white blood cells count (WBC) and fever], increased PCT, increased WBC and fever were demonstrated to be independent risk factors for sepsis in the logistic equation. The AUC for the new combined predictive indicator was higher than that of any other indictor, including PCT, LPS, infection, WBC and fever (0.930 vs. 0.661, 0.503, 0.570, 0.837, 0.800). The optimal cut-off value for the new combined predictive indicator was 0.518. Using the new indicator to diagnose sepsis, the sensitivity, specificity and diagnostic accuracy

  13. Efficacy Evaluation of a Multifunctional Cosmetic Formulation: The Benefits of a Combination of Active Antioxidant Substances

    Directory of Open Access Journals (Sweden)

    Mirela D. Gianeti

    2014-11-01

    Full Text Available This study presents the association of active antioxidants substances in a multifunctional cosmetic formulation with established efficacy against signs of aging. A multifunctional cosmetic formulation containing an association of UV filters and antioxidant substances (liposoluble vitamins A, C and E, Ginkgo biloba and Phorphyra umbilicalis extracts was evaluated. This formulation was submitted to a clinical efficacy study using biophysics techniques and skin images analysis (digital photography imaging systems, 20 MHz ultrasound, and reflectance confocal microscopy. The volunteers applied the formulation containing the UV filters and antioxidant substances during the day and the formulation with antioxidant substances and without the UV filters at night, for 90 days. The formulation increased the hydration and protected the skin barrier function after a single application. At the long term assessment the formulation provided an improvement in skin barrier function and skin hydration to the deeper layers of the epidermis, leading to an improvement in skin appearance by reducing wrinkles and skin roughness. The multifunctional cosmetic formulation studied can be suggested to preventing signs of aging and improving skin conditions. In addition, this study presents the benefits of associating different active antioxidants substances in a single cosmetic formulation to prevent skin aging.

  14. Combinational enhancing effects of formulation and encapsulation on digestive stability and intestinal transport of green tea catechins.

    Science.gov (United States)

    Son, Yu-Ra; Chung, Jae-Hwan; Ko, Sanghoon; Shim, Soon-Mi

    2016-01-01

    The hypothesis was that green tea catechins (GTCs) formulated with vitamin C and xylitol followed by enteric coating with hydroxypropyl methyl cellulose phthalate (HPMCP) or encapsulated into γ-cyclodextrin (γ-CD) could enhance intestinal absorption of GTCs. Surface morphology and size obtained by SEM were different. Digestive stability of GTCs encapsulated into γ-CD or coated with HPMCP was enhanced up to 65.56% or 57.63%, respectively. When GTCs were formulated, the digestive stability was greater than the one not formulated. Formulated GTCs followed by encapsulation into γ-CD significantly increased intestinal transport. Absorption of GTCs was 2.8%, 9.64%, 11.97%, 8.41% and 14.36% for only GTCs, GTCs encapsulated into γ-CD, formulated GTCs encapsulated into γ-CD, GTCs coated with HPMCP and formulated GTCs coated with HPMCP, respectively. This study suggests that GTCs, formulated with vitamin C and xylitol followed by γ-CD encapsulation or HPMCP enteric coating, provide combinational effect to increase bioavailability of GTCs.

  15. Simple field assays to check quality of current artemisinin-based antimalarial combination formulations.

    Directory of Open Access Journals (Sweden)

    Jean-Robert Ioset

    Full Text Available INTRODUCTION: Malaria continues to be one of the major public health problems in Africa, Asia and Latin America. Artemisinin derivatives (ARTs; artesunate, artemether, and dihydroartemisinin derived from the herb, Artemisia annua, are the most effective antimalarial drugs available providing rapid cures. The World Health Organisation (WHO has recommended that all antimalarials must be combined with an artemisinin component (artemisinin-based combination therapy; ACT for use as first line treatment against malaria. This class of drugs is now first-line policy in most malaria-endemic countries. Reports of ad hoc surveys from South East Asia show that up to 50% of the artesunate currently sold is counterfeit. Drug quality is rarely assessed in resource poor countries in part due to lack of dedicated laboratory facilities which are expensive to build, equip and maintain. With a view to address this unmet need we developed two novel colour reaction assays that can be used in the field to check the quality of ARTs. METHODS AND FINDINGS: Our assays utilise thin layer chromatography silica gel sheets and 2, 4 dinitrophenylhydrazine or 4-Benzoylamino-2, 5-dimethoxybenzenediazonium chloride hemi (zinc chloride salt as the reagents showing a pink or blue product respectively only in the presence ARTs. We are able to detect as low as 10% of ARTs in ACTs (WINTHROP--artesunate/amodiaquine, Coartem--artemether/lumefantrine and Duocortexcin--dihydroartemisinin/piperaquine. The assays have been validated extensively by testing eighty readily accessible and widely used drugs in malaria endemic countries. None of the other antimalarial drugs or a range of commonly used excipients, antiretroviral drugs or other frequently used drugs from the WHO essential drugs list such as analgesics or antibiotics are detected with our assays. CONCLUSIONS: Our two independent assays requiring no specialist training are specific, simple to use, rapid, robust, reproducible

  16. Simple field assays to check quality of current artemisinin-based antimalarial combination formulations.

    Science.gov (United States)

    Ioset, Jean-Robert; Kaur, Harparkash

    2009-09-30

    Malaria continues to be one of the major public health problems in Africa, Asia and Latin America. Artemisinin derivatives (ARTs; artesunate, artemether, and dihydroartemisinin) derived from the herb, Artemisia annua, are the most effective antimalarial drugs available providing rapid cures. The World Health Organisation (WHO) has recommended that all antimalarials must be combined with an artemisinin component (artemisinin-based combination therapy; ACT) for use as first line treatment against malaria. This class of drugs is now first-line policy in most malaria-endemic countries. Reports of ad hoc surveys from South East Asia show that up to 50% of the artesunate currently sold is counterfeit. Drug quality is rarely assessed in resource poor countries in part due to lack of dedicated laboratory facilities which are expensive to build, equip and maintain. With a view to address this unmet need we developed two novel colour reaction assays that can be used in the field to check the quality of ARTs. Our assays utilise thin layer chromatography silica gel sheets and 2, 4 dinitrophenylhydrazine or 4-Benzoylamino-2, 5-dimethoxybenzenediazonium chloride hemi (zinc chloride) salt as the reagents showing a pink or blue product respectively only in the presence ARTs. We are able to detect as low as 10% of ARTs in ACTs (WINTHROP--artesunate/amodiaquine, Coartem--artemether/lumefantrine and Duocortexcin--dihydroartemisinin/piperaquine). The assays have been validated extensively by testing eighty readily accessible and widely used drugs in malaria endemic countries. None of the other antimalarial drugs or a range of commonly used excipients, antiretroviral drugs or other frequently used drugs from the WHO essential drugs list such as analgesics or antibiotics are detected with our assays. Our two independent assays requiring no specialist training are specific, simple to use, rapid, robust, reproducible, inexpensive and, have successfully resulted in detecting two

  17. Sublingual injection of microparticles containing glycolipid ligands for NKT cells and subunit vaccines induces antibody responses in oral cavity.

    Science.gov (United States)

    DeLyria, Elizabeth S; Zhou, Dapeng; Lee, Jun Soo; Singh, Shailbala; Song, Wei; Li, Fenge; Sun, Qing; Lu, Hongzhou; Wu, Jinhui; Qiao, Qian; Hu, Yiqiao; Zhang, Guodong; Li, Chun; Sastry, K Jagannadha; Shen, Haifa

    2015-03-20

    Natural Killer T (NKT) cells are a unique type of innate immune cells which exert paradoxical roles in animal models through producing either Th1 or Th2 cytokines and activating dendritic cells. Alpha-galactosylceramide (αGalCer), a synthetic antigen for NKT cells, was found to be safe and immune stimulatory in cancer and hepatitis patients. We recently developed microparticle-formulated αGalCer, which is selectively presented by dendritic cells and macrophages, but not B cells, and thus can avoid the anergy of NKT cells. In this study, we have examined the immunogenicity of microparticles containing αGalCer and protein vaccine components through sublingual injection in mice. The results showed that sublingual injection of microparticles containing αGalCer and ovalbumin triggered IgG responses in serum (titer >1:100,000), which persisted for more than 3months. Microparticles containing ovalbumin alone also induced comparable level of IgG responses. However, immunoglobulin subclass analysis showed that sublingually injected microparticles containing αGalCer and ovalbumin induced 20 fold higher Th1 biased antibody (IgG2c) than microparticles containing OVA alone (1:20,000 as compared to 1:1000 titer). Sublingual injection of microparticles containing αGalCer and ovalbumin induced secretion of both IgG (titer >1:1000) and IgA (titer=1:80) in saliva secretion, while microparticles containing ovalbumin alone only induced secretion of IgG in saliva. Our results suggest that sublingual injection of microparticles and their subsequent trafficking to draining lymph nodes may induce adaptive immune responses in mucosal compartments. Ongoing studies are focused on the mechanism of antigen presentation and lymphocyte biology in the oral cavity, as well as the toxicity and efficacy of these candidate microparticles for future applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Warfarin induced sublingual hematoma: a Ludwig angina mimic.

    Science.gov (United States)

    Pathak, Ranjan; Supplee, Suzanne; Aryal, Madan Raj; Karmacharya, Paras

    2015-01-01

    Sublingual hematoma is a rare but life-threatening complication of oral anticoagulants. It is important to differentiate this from infectious processes like Ludwig's angina. Securing the airway should be a priority and immediate reversal of anticoagulation with close monitoring is required. We present a case of sublingual hematoma secondary to warfarin therapy without airway compromise which was managed conservatively with reversal of INR with oral vitamin K. Although rare, it is crucial to differentiate sublingual hematomas from infectious processes. Reversal of anticoagulation with low threshold for artificial airway placement in the event of airway compromise is the treatment of choice. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Male oriental fruit moth response to a combined pheromone-based attracticide formulation targeting both oriental fruit moth and codling moth (Lepidoptera: Tortricidae).

    Science.gov (United States)

    Evenden, Maya L; McClaughlin, John R

    2005-04-01

    Combined attracticide formulations targeting Oriental fruit moth, Grapholita molesta (Busck), and codling moth, Cydia pomonella (L.), were tested in a field trapping experiment. Capture of male codling moths in traps baited with the combined formulation was reduced compared with traps baited with the codling moth formulation alone, whereas capture of male Oriental fruit moth was increased compared with traps baited with the Oriental fruit moth formulation alone. Subsequent wind tunnel experiments showed that a single locus of the mixed attracticide formulation or close parallel presentation of the two formulations enhanced source contact by male Oriental fruit moths but did not influence earlier behaviors. However, the two formulations presented in a serial arrangement to Oriental fruit moth males in the wind tunnel resulted in enhanced lock-on, upwind flight, and source contact behaviors. In addition, male Oriental fruit moths remained on mixed pheromone droplets of the paste matrix longer than on droplets of the Oriental fruit moth formulation alone. The increased time spent on the mixed droplet was correlated with a more rapid poisoning and a greater proportion of poisoned males compared with males exposed to the Oriental fruit moth attracticide alone. These results demonstrate that a combined attracticide formulation will have different effects on each of the targeted species. It is anticipated that, due to decreased attractiveness, a combined formulation would be less effective against the codling moth. However, a mixed formulation, due to increased attractiveness and toxicity, could be more effective against the Oriental fruit moth under field conditions.

  20. Gum pigmentation: an unusual adverse effect of sublingual immunotherapy

    OpenAIRE

    Goh, Anne; Chiang, Wen Chin; Kang, Liew Woei; Rao, Rajeshwar; Lim, Hwee Hoon; Chng, Chai Kiat

    2014-01-01

    Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is...

  1. Same effect of sublingual and oral captopril in hypertensive crisis.

    Science.gov (United States)

    Karakiliç, E; Büyükcam, F; Kocalar, G; Gedik, S; Atalar, E

    2012-11-01

    Hypertensive crisis is a condition characterized by rapid and inappropriate symptomatic elevation of blood pressure (BP) that is commonly seen in Emergency Departments. Oral or sublingual captopril is commonly used in the Emergency Departments. The unpleasant taste of the sublingual drugs causes uncomfortable condition to the patient. Studies showing no difference between oral and sublingual captopril has been ignored so far. Herein we compared the oral and sublingual captopril efficiency in the hypertensive urgencies. In this retrospective observational study, 71 patients admitted with hypertensive urgency to Emergency Departments of two hospitals in 2011 whose blood pressure were recorded before captopril administration and blood pressure were recorded after captopril administration at 0-5-15-30-45-60 minutes were included the study. The reductions of the blood pressure of oral and sublingual captopril groups were compared. There were 28 patients at oral and 43 at sublingual captopril group. The mean age ± SD was 58.13 ± 8.66 years and 41 (57.7%) patients were female. The most common complaints were headache, nausea/vomiting and weakness. 65 (91.5%) patients were using antihypertensive drugs before admitted to hospital. The blood pressure at 0, 5, 15, 30, 45 and 60th minutes of therapy didn't show any difference between oral and sublingual captopril use. There was any difference between oral and sublingual captopril efficiency to control of hypertension in patient with hypertensive urgency. For a more comfortable treatment, oral captopril may be a more convenient choice in the hypertensive urgencies.

  2. Debut of Gastroesophageal Reflux Concomitant with Administration of Sublingual Immunotherapy

    DEFF Research Database (Denmark)

    Juel, J.

    2017-01-01

    , and dysphagia. Sublingual immunotherapy (SLIT) was first described in 1986. Following this description, the use has greatly increased in the treatment of allergic rhinitis, as an alternative to subcutaneously administered immunotherapy. Side effects are commonly of oropharyngeal and gastrointestinal nature...... to administration of sublingual immunotherapy for house dust mite in allergic rhinitis. The patient had to stop the SLIT after two weeks of administration due to GORD. The cessation resulted in rapid resolution of symptoms....

  3. Sublingual immunotherapy: World Allergy Organization position paper 2013 update

    Science.gov (United States)

    2014-01-01

    We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations. Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. PMID:24679069

  4. NUT Carcinoma of the Sublingual Gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; French, C A; Josiassen, Michael

    2016-01-01

    NUT carcinoma (NC) is a recently described, rare and extremely aggressive cancer primarily located to supradiaphragmatic structures and affecting young individuals. NC is characterized by translocations involving the NUT gene on 15q14 with the most common translocation partner gene being BRD4 on 19......p13, resulting in the t(15;19)(q14;p13) karyotype. NC is poorly differentiated and is likely to be overlooked and misdiagnosed as poorly differentiated squamous cell carcinoma (SCC) when immunohistochemical evaluation of NUT protein expression is omitted. Previously, NC has been found in the parotid...... and submandibular glands and we present the first case in the sublingual gland arising in a 40-year-old woman. We discuss the diagnostic considerations for poorly differentiated carcinomas of the salivary glands and advocate the inclusion of NUT immunohistochemistry in this setting. Not only does the NC diagnosis...

  5. SUBLINGUAL BUPRENORPHINE VS MIDAZOLAM FOR PREMEDICATION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V.A HASANI

    2000-03-01

    Full Text Available Background. Preanesthetic medication may reduce the risks of adverse psychological and physiological sequel of induction in children. Administration of premedication by sublingual route may provide the best compromise because of relatively rapid absorption without causing pain. In this study sedative and anxitolytic effects of sublingual midazolam and buprenorphine in children were compared. Methods. In a randomized, controlled, double blind clinical trial, one hundred and fifty children aged between 4 to 10 years in first or second class of ASA scheduled for adenotonsillectomy were divided in three equal groups. These groups recieved sublingual bupronorphine 3 µg/kg, midazolam 0.2 mg/kg and no premedication respectively. Cardiorespiratory variables were recorded from the time of premedication to awakening from anesthesia. Anxiety and sedation scores and patients acceptance of mask at induction were recorded using four point rating scales. Time of spontaneous eye opening and postoperative emesis occurrence were also recorded. Findings. Children recieving sublingual midazolam or buprenorphine had similar sedation, anxiety and mask acceptance scores, but different from no premedication group (P < 0.0001. None of the children experienced respiratory depression or oxygen desaturation after drug administration and during postoperative period. Time of spontaneous eye opening was longer in the midazolam group (P < 0.0001.Emetic episodes were similar in all groups. Conclusion. Midazolam is extensively studied and demonstrated that the drug is highly effective in alleviating anxiety and increasing cooperation. We concluded that sublingual buprenorphine is as effective as sublingual midazolam in providing sedation and anxitolysis for pediatric premedication.

  6. Clindamycin phosphate-tretinoin combination gel revisited: status report on a specific formulation used for acne treatment.

    Science.gov (United States)

    Del Rosso, James Q

    2017-03-01

    Topical agents, including retinoids and antibiotics, are commonly used to treat acne vulgaris (AV) and remain as components of acne treatment guidelines. Approved topical combination formulations offer the advantages of established efficacy, decreased frequency of application, and improved convenience for patients. This article discusses both clindamycin phosphate (CP) and tretinoin (Tret) as components of a topical aqueous-based combination gel that has been shown to be effective, safe, and well tolerated for treatment of facial AV. Clinically relevant considerations with use of this treatment are also discussed, including therapeutic advantages and potential limitations.

  7. Sublingual ketorolac and sublingual piroxicam are equally effective for postoperative pain, trismus, and swelling management in lower third molar removal.

    Science.gov (United States)

    Trindade, Paulo A K; Giglio, Fernando P M; Colombini-Ishikiriama, Bella L; Calvo, Adriana M; Modena, Karin Cristina S; Ribeiro, Debora A; Dionísio, Thiago J; Brozoski, Daniel T; Lauris, José Roberto P; Faria, Flávio Augusto C; Santos, Carlos F

    2012-07-01

    Lower third molar removal provides a clinical model for studying analgesic drugs. The present study's aim was to compare the clinical efficacy of sublingual ketorolac and sublingual piroxicam in managing pain, trismus and swelling after lower third molar extraction in adult volunteers. In this double-blinded, randomized, crossover investigation, 47 volunteers received for 4 days ketorolac sublingually (10 mg 4 times daily) and piroxicam sublingually (20 mg once daily) during 2 separate appointments after lower third molar extraction of symmetrically positioned lower third molars. A surgeon evaluated objective parameters (surgery duration, mouth opening, rescue analgesic medication, and facial swelling) and volunteers documented subjective parameters (postoperative pain and global evaluation), comparing postoperative results for a total of 7 days after surgery. The means of the objective and subjective parameters were compared for statistical significance (P .05). Additionally, values for mouth openings measured just before surgery and immediately after suture removal 7 days later were similar among volunteers (P > .05), and the type of nonsteroidal antiinflammatory drug (NSAID) used in this study showed no significant differences between swellings on the second or seventh days after surgery (P > .05). Pain, trismus, and swelling after lower third molar extraction, independent of surgical difficulty, were successfully controlled by sublingual ketorolac (10 mg 4 times daily) or sublingual piroxicam (20 mg once daily), and no significant differences were observed between the NSAIDs evaluated. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy

    Directory of Open Access Journals (Sweden)

    Liu Feng

    2010-11-01

    Full Text Available Abstract Background Schistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. Although there are no vaccines available to date, this strategy appears feasible since natural immunity develops in individuals suffering from repeated infection during a lifetime. Since vaccinations resulting in both Th1- and Th2-type responses have been shown to contribute to protective immunity, a vaccine formulation with the capacity for stimulating multiple arms of the immune response will likely be the most effective. Previously we developed partially protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV (T3-PDDV and B3-PDDV, respectively capable of eliciting immune responses against the Schistosoma japonicum 22.6 kDa tegument antigen (Sj22.6 and a 62 kDa fragment of myosin (Sj62, respectively. Results In this study, we developed PDDV cocktails containing multiple epitopes of S. japonicum from Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potential in vivo. Results showed that mice immunized with a single-epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice immunized with either the T3- or B3- single-epitope PDDV formulation were partially protected against infection. However, mice immunized with a multicomponent (3 PDDV components formulation elicited variable immune responses that were less immunoprotective than single-epitope PDDV formulations. Conclusions Our data show that combining these different antigens did not result in a more effective vaccine formulation when compared to each component administered individually, and further suggest that immune interference resulting from immunizations with antigenically distinct vaccine targets may be an important consideration in the development of multicomponent vaccine preparations.

  9. Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen

    DEFF Research Database (Denmark)

    Aliu, Have; Rask, Carola; Brimnes, Jens

    2017-01-01

    Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the - treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development...

  10. Efficacy of Combined Formulations of Fungicides with Different Modes of Action in Controlling Botrytis Gray Mold Disease in Chickpea

    Directory of Open Access Journals (Sweden)

    M. H. Rashid

    2014-01-01

    Full Text Available Botrytis gray mold (BGM caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L. and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur in Bangladesh for three years (2008, 2009, and 2010. Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%, and Protaf 250EC, propiconazole (0.05%], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%; Secure 600 WG, phenomadone + mancozeb (0.2%; and Companion, mancozeb 63% + carbendazim 12% (0.2%]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1–9 scale and the highest increase (38% of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance.

  11. A finite element formulation with combined loadings for shear dominant RC structures.

    Science.gov (United States)

    2008-08-01

    Inelastic failure of reinforced concrete (RC) structures under seismic loadings can be due either to loss of flexural, shear or bond : capacity. Specifically, the effect of combined loadings can lead to a complex failure mechanism that plays a vital ...

  12. The role of combination anthelmintic formulations in the sustainable control of sheep nematodes.

    Science.gov (United States)

    Bartram, David J; Leathwick, Dave M; Taylor, Mike A; Geurden, Thomas; Maeder, Steven J

    2012-05-25

    Combinations of anthelmintics with a similar spectrum of activity and different mechanisms of action and resistance are widely available in several regions of the world for the control of sheep nematodes. There are two main justifications for the use of such combinations: (1) to enable the effective control of nematodes in the presence of single or multiple drug resistance, and (2) to slow the development of resistance to the component anthelmintic classes. Computer model simulations of sheep nematode populations indicate that the ability of combinations to slow the development of resistance is maximised if certain prerequisite criteria are met, the most important of which appear to concern the opportunity for survival of susceptible nematodes in refugia and the pre-existing levels of resistance to each of the anthelmintics in the combination. Combinations slow the development of a resistant parasite population by reducing the number of resistant genotypes which survive treatment, because multiple alleles conferring resistance to all the component anthelmintic classes must be present in the same parasite for survival. Individuals carrying multiple resistance alleles are rarer than those carrying single resistance alleles. This enhanced efficacy leads to greater dilution of resistant genotypes by the unselected parasites in refugia, thus reducing the proportion of resistant parasites available to reproduce with other resistant adults that have survived treatment. Concerns over the use of anthelmintic combinations include the potential to select for resistance to multiple anthelmintic classes concurrently if there are insufficient parasites in refugia; the potential for shared mechanisms of resistance between chemical classes; and the pre-existing frequency of resistance alleles may be too high on some farms to warrant the introduction of certain combinations. In conclusion, anthelmintic combinations can play an important role in resistance management. However, they

  13. Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization

    Science.gov (United States)

    Gupta, M. M.; Gupta, Niraj; Chauhan, Bhupendra S.; Pandey, Shweta

    2014-01-01

    The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC). The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP), croscarmellose sodium (CCM), and sodium starch glycolate (SSG) as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT), and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results. PMID:26556198

  14. Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization

    Directory of Open Access Journals (Sweden)

    M. M. Gupta

    2014-01-01

    Full Text Available The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC. The tablets were prepared using microcrystalline cellulose (MCC PH 102 as diluent along with crospovidone (CP, croscarmellose sodium (CCM, and sodium starch glycolate (SSG as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT, and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.

  15. Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization.

    Science.gov (United States)

    Gupta, M M; Gupta, Niraj; Chauhan, Bhupendra S; Pandey, Shweta

    2014-01-01

    The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC). The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP), croscarmellose sodium (CCM), and sodium starch glycolate (SSG) as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT), and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.

  16. Characterization and formulation of a new eco-friendly hydraulic binder based on combination of inorganic and organic admixtures

    Directory of Open Access Journals (Sweden)

    Khudhair M.H.R.

    2018-01-01

    Full Text Available This work aims to valorize a mineral and natural resources such as the Limestone Fillers (F-Lime and the Natural Pozzolan (PN by incorporating them into the formulation matrix of cement or concrete. In order to minimize the CO2 emissions into the atmosphere, to reduce the energy and raw materials consumption and as well as, to improve the physical and mechanical properties in fresh cement paste and of mortar or concrete in the hardened state. In this present manuscript, we substituted the clinker by the combination between the F-Lime and NP at 40% by weight of cement with steps of 5% with the admixture of superplasticizers. The influences of the incorporation of these additions on physical and mechanical properties of mortar or concrete in the fresh cement paste and hardened state were evaluated. The obtained results by different formulations elaborated to show that the replacement a part of clinker by the mixing of F-Lime and PN has produced a new hydraulic binder eco-friendly and durable with improved physicochemical, physical and mechanical properties. These results show that we have succeeded to manufacture, characteristic and formulated of new ecofriendly hydraulic binder and sustainable with improved physical, chemical, and mechanical properties while minimizing greenhouse gas emissions on one hand and the reducing the energy raw materials consumption on the other hand.

  17. Sublingual Immunotherapy in Children: An Updated Review

    Directory of Open Access Journals (Sweden)

    Chang-Hung Kuo

    2009-04-01

    Full Text Available Although pharmacological therapy and allergen avoidance are effective means of managing allergic disease, allergen-specific immunotherapy is able to treat not only the symptoms, but also the underlying causes of the disease. Sublingual immuno-therapy (SLIT has been shown to be effective in patients with allergic diseases. It has demonstrated long-term clinical benefits and shown the potential to modify the course of allergic disease in children with rhinitis, conjunctivitis, and asthma. The precise mechanisms of SLIT remain unclear, but antigen-presenting cells in the oral mucosa may induce regulatory T-cells that suppress the allergic immune response by increasing production of interleukin-10. SLIT has also been shown to increase allergen-specific IgG antibodies that antagonize and block the allergic response. SLIT was well tolerated in all reported, double-blinded, placebo-controlled, randomized trials. SLIT is an ideal means of treating the pediatric population because of its excellent safety and good compliance. However, the optimal dose and duration of SLIT require further investigation.

  18. Formulating powder-device combinations for salmeterol xinafoate dry powder inhalers.

    Science.gov (United States)

    Hassoun, Mireille; Ho, Shirlene; Muddle, Joanna; Buttini, Francesca; Parry, Mark; Hammond, Mark; Forbes, Ben

    2015-07-25

    Using salmeterol xinafoate (SX) as an active pharmaceutical ingredient, the effects of carrier lactose particle type, total lactose fines content and device resistance on dry powder inhaler performance were investigated in vitro. To mimic drug levels in commercial preparations, interactive mixtures containing 0.58% w/w SX were prepared by low shear tumble mixing. Three types of milled inhalation grade lactose were used (Lactohale(®) LH 200, Respitose(®) ML006 and ML001) and the concentration of fine lactose (Lactohale(®) 300) added was varied. The in vitro deposition of each mixture was studied using a next generation impactor and inhaler devices exhibiting different resistances, Rotahaler(®)MMAD) ± geometric standard deviation (GSD) and fine particle fraction (FPF). Increases of up to eight-fold in FPF were observed with increasing intrinsic fine lactose content. The addition of extra fine lactose increased the FPF further, although the effect diminished as more fines were added. The Aerolizer produced the best aerosol performance with any given powder blend, although suitable formulations were identified for each device as defined by the a priori success criteria: >80% ED and MMAD ± GSD between 1-5 μm. The results confirmed the factors under investigation to be important determinants of product performance, but demonstrated using realistic conditions how individual factor impact may be enhanced or mitigated by inter-dependency. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Sublingual Microcirculation is Impaired in Post-cardiac Arrest Patients

    DEFF Research Database (Denmark)

    G. Omar, Yasser; Massey, Michael; Wiuff Andersen, Lars

    2013-01-01

    the microcirculation flow index (MFI) at 6 and 24h in the cardiac arrest patients, and within 6h of emergency department admission in the sepsis and control patients. RESULTS: We evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual...... markers in the post-cardiac arrest state. METHODS: We prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using Sidestream Darkfield microscopy. Microcirculatory flow was assessed using...

  20. Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine.

    Science.gov (United States)

    Ott, J

    2001-01-01

    Summarized are psychonautic bioassays (human self-experiments) of pharmepéna--crystalline 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-Me-bufotenine), at times combined with crystalline beta-carbolines (harmaline or harmine). These substances were administered via intranasal, sublingual and oral routes, by way of pharmacological modeling of diverse South American shamanic inebriants (principally the snuffs epéna/nyakwana, prepared from barks of diverse species of Virola.) Intranasal, sublingual and oral psychoactivity of 5-MeO-DMT, and the 1967 Holmstedt-Lindgren hypothesis of the paricá-effect--intranasal potentiation of tryptamines by concomitant administration of monoamine-oxidase-inhibiting (MAOI) beta-carbolines from stems of Banisteriopsis caapi admixed with the snuffs--have been confirmed by some 17 psychonautic bioassays. Salient phytochemical and psychonautic literature is reviewed.

  1. Investigation of the enhanced antimicrobial activity of combination dry powder inhaler formulations of lactoferrin.

    Science.gov (United States)

    Marshall, Lindsay J; Oguejiofor, Wilson; Price, Robert; Shur, Jagdeep

    2016-12-05

    The airways of most people with cystic fibrosis are colonized with biofilms of the Gram-negative, opportunistic pathogen Pseudomonas aeruginosa. Delivery of antibiotics directly to the lung in the form of dry powder aerosols offers the potential to achieve high local concentrations directly to the biofilms. Unfortunately, current aerosolised antibiotic regimes are unable to efficiently eradicate these biofilms from the airways. We investigated the ability of the innate antimicrobial, lactoferrin, to enhance the activity of two aminoglycoside antibiotics (tobramycin and gentamicin) against biofilms of P. aeruginosa strain PAO1. Biofilms were prepared in 96 well polystyrene plates. Combinations of the antibiotics and various lactoferrin preparations were spray dried. The bacterial cell viability of the various spray dried combinations was determined. Iron-free lactoferrin (apo lactoferrin) induced a 3-log reduction in the killing of planktonic cell by the aminoglycoside antibiotics (plactoferrin and an aminoglycoside displays potential as an effective new therapeutic strategy in the treatment of P. aeruginosa biofilms infections such as those typical of the CF lungs. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. [Polymorphic light eruption: prophylaxis using a topical combination of antioxidants and UVA protection formulations].

    Science.gov (United States)

    Jeanmougin, M; Peyron, J-L; Thomas, P; Beani, J-C; Guez, E; Bachot, N

    2006-05-01

    In a recent randomized, double-blind, placebo-controlled clinical study, the efficacy of a combination consisting of 0.25% alpha-glucosyl-rutin, 1% vitamin E and a broad-spectrum, highly UVA-protective sunscreen (sun protector factor 15 - persistent pigmentation darkening 6) regarding prevention of polymorphous light eruption was well demonstrated. We evaluated this combination under real solar exposure conditions. Patients with three previous typical polymorphous light eruptions (including one in the last year) were included in an open prospective multicenter study. The preparation was applied every two hours after the first summer exposure. No topical or systemic treatments presumed to be effective against polymorphous light eruption were given concomitantly. Evaluation was performed after the summer by a dermatologist. Two of the 54 patients dropped out of the study, one for an adverse effect (contact dermatitis). At the end of the study following application of the test preparation, no eruption was seen for 35 patients (67%), with minor eruption for 10 patients (19%) and an marked eruption for 7 patients (13%). Pruritus (present in all patients the year before) was not seen in 36 patients (69%), was considered bearable for 36 patients and unbearable for only 3 patients compared to 27 before inclusion. For the dermatologists, efficacy was excellent for 35 patients and good for 7 patients, giving global efficacy of around 80%, with inadequate results in 10% of cases (5 patients). Concerning protection against erythema, the test product reduced sunburn by 60% compared with the previous year. Because of the high clinical efficacy of the product noted after UVA challenge tests and verified by this clinical study under actual conditions of exposure, it may be proposed as a new prophylactic treatment for polymorphous light eruption.

  3. A combined analytical formulation and genetic algorithm to analyze the nonlinear damage responses of continuous fiber toughened composites

    Science.gov (United States)

    Jeon, Haemin; Yu, Jaesang; Lee, Hunsu; Kim, G. M.; Kim, Jae Woo; Jung, Yong Chae; Yang, Cheol-Min; Yang, B. J.

    2017-09-01

    Continuous fiber-reinforced composites are important materials that have the highest commercialized potential in the upcoming future among existing advanced materials. Despite their wide use and value, their theoretical mechanisms have not been fully established due to the complexity of the compositions and their unrevealed failure mechanisms. This study proposes an effective three-dimensional damage modeling of a fibrous composite by combining analytical micromechanics and evolutionary computation. The interface characteristics, debonding damage, and micro-cracks are considered to be the most influential factors on the toughness and failure behaviors of composites, and a constitutive equation considering these factors was explicitly derived in accordance with the micromechanics-based ensemble volume averaged method. The optimal set of various model parameters in the analytical model were found using modified evolutionary computation that considers human-induced error. The effectiveness of the proposed formulation was validated by comparing a series of numerical simulations with experimental data from available studies.

  4. Sublingual lorazepam in the treatment of familial paroxysmal nonkinesigenic dyskinesia.

    Science.gov (United States)

    Dooley, Joseph M; Brna, Paula M

    2004-05-01

    Familial paroxysmal nonkinesigenic dyskinesia (Mount and Reback syndrome) is characterized by episodes of dystonia and chorea, which are precipitated by fatigue, emotional stress, alcohol, or foods. We report two children from a large kindred with this condition who responded to sublingual lorazepam.

  5. Abnormal blood flow in the sublingual microcirculation at high altitude

    NARCIS (Netherlands)

    Martin, Daniel S.; Ince, Can; Goedhart, Peter; Levett, Denny Z. H.; Grocott, Mike P. W.

    2009-01-01

    We report the first direct observations of deranged microcirculatory blood flow at high altitude, using sidestream dark-field imaging. Images of the sublingual microcirculation were obtained from a group of 12 volunteers during a climbing expedition to Cho Oyu (8,201 m) in the Himalayas.

  6. CONGENITAL SUBLINGUAL DERMOID CYST IN A NEONATE: A ...

    African Journals Online (AJOL)

    there is no embryologic link between the two lesions. The differential diagnosis of dermoid cysts of floor of mouth include ranula, thyroglossal duct cyst, cystic hygroma, sialolithiasis or infection of the sublingual and submandibular glands, acute infection or cellulitis of the floor of mouth, benign. Tumours (eg. lipoma, fibroma, ...

  7. Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners.

    Science.gov (United States)

    Pranskunas, Andrius; Arstikyte, Justina; Pranskuniene, Zivile; Bernatoniene, Jurga; Kiudulaite, Inga; Vaitkaitiene, Egle; Vaitkaitis, Dinas; Brazaitis, Marius

    2017-01-01

    We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37 ± 30.2 versus 221.80 ± 23.4 min, p = 0.045), ingested less fluids (907 ± 615 versus 1950 ± 488 mL, p = 0.007) during the race, and lost much more weight (-2.4 ± 1.3 versus -1.0 ± 0.8 kg, p = 0.041). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.

  8. Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners

    Directory of Open Access Journals (Sweden)

    Andrius Pranskunas

    2017-01-01

    Full Text Available We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands, and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km, directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37±30.2 versus 221.80±23.4 min, p=0.045, ingested less fluids (907±615 versus 1950±488 mL, p=0.007 during the race, and lost much more weight (-2.4±1.3 versus -1.0±0.8 kg, p=0.041. Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.

  9. Optimization of formulation of soy-cakes baked in infrared-microwave combination oven by response surface methodology.

    Science.gov (United States)

    Şakıyan, Özge

    2015-05-01

    The aim of present work is to optimize the formulation of a functional cake (soy-cake) to be baked in infrared-microwave combination oven. For this optimization process response surface methodology was utilized. It was also aimed to optimize the processing conditions of the combination baking. The independent variables were the baking time (8, 9, 10 min), the soy flour concentration (30, 40, 50 %) and the DATEM (diacetyltartaric acid esters of monoglycerides) concentration (0.4, 0.6 and 0.8 %). The quality parameters that were examined in the study were specific volume, weight loss, total color change and firmness of the cake samples. The results were analyzed by multiple regression; and the significant linear, quadratic, and interaction terms were used in the second order mathematical model. The optimum baking time, soy-flour concentration and DATEM concentration were found as 9.5 min, 30 and 0.72 %, respectively. The corresponding responses of the optimum points were almost comparable with those of conventionally baked soy-cakes. So it may be declared that it is possible to produce high quality soy cakes in a very short time by using infrared-microwave combination oven.

  10. Effects of Sublingual Captopril in Immediate Treatment of Hypertensive Crisis

    Directory of Open Access Journals (Sweden)

    H. Kazerani

    2007-04-01

    Full Text Available Introduction & Objective: Sublingual captopril was shown to be a safe and effective drug to control hypertensive urgencies. However the exact time and efficacy of lowering blood pressure (BP is a matter of interest and importance. In this study we evaluated the time and efficacy of 25 mg sublingual captopril in lowering blood pressure. Materials & Methods: In a randomized clinical trial 101 patients (34 men, 67 women with blood pressure of 180/110 mmHg (or more who had no finding of major organ damage (heart – brain -eyes –renal were studied by prescription of 25 mg sublingual captopril. Then systolic and diastolic blood pressure was measured at 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 105, 120 minutes following drug administration. Data analysis was performed using paired t-test and SPSS software. Results: The results showed that almost all the patients had some decrease in BP. After 120 minutes blood pressure dropped about 5% in 30%, and 5-30% in 70% of patients, compared to first measured BP. Maximal effect was observed in 25-30 minutes after drug administration: after 30 minutes systolic pressure dropped in 68.4% and diastolic pressure in 65.3% of patients about 5-25%. 47 patients had low response to therapy after 60 minutes, so they received another 25 mg captopril sublingual, which BP dropped in 45% of them. 19 patients were prescribed IV furosemide after 120 minutes. This group had resistant HTN and 25 cases of them were treated with ACEI previously. BP decreased gradually and not more than 30% of first BP. None of the patients encountered side effects. Conclusion: Sublingual captopril is a good, safe, effective, available and cost effective drug, with very low side effects in treating patients with hypertensive crisis. It is recommended to use this drug instead of Nifedipine in all hypertensive patients.

  11. Clinical evaluation of sublingual administration of dust mite drops in the treatment of allergic asthma and allergic rhinitis of children.

    Science.gov (United States)

    Yin, G-Q; Jiang, W-H; Wu, P-Q; He, C-H; Chen, R-S; Deng, L

    2016-10-01

    This study focuses on evaluating the clinical effects of sublingual dust mite drops for the treatment of allergic asthma in children. 156 pediatric patients with allergic rhinitis and asthma were randomly divided into control and observation groups (78 cases each). For the control group the standard global initiative for asthma (GINA) asthma control scheme was adopted; meanwhile, the observation group patients received the standard GINA combined with sublingual administration of dust mite drops, once per day, gradually increasing the dose to reach a high maintenance level. After six months the sublingual drops were stopped and then the effects of the treatments on both groups of patients were compared. The symptoms of asthma and rhinitis in the daytime and nighttime for both groups decreased gradually with time. However, the observation group's outcome at the 6th, 12th and 24th month were significantly better than those of the control group (p 0.05). But at the 24th month, the observation group had significantly higher rates of complete and good control (p 0.05); however, the levels of IL-2 increased gradually and improved more in the observation group (p allergic rhinitis and asthma can improve clinical symptoms, increase the efficiency rate and increase the serum IL-2 level, and does not cause an increase in adverse reactions or IgE levels in treated children.

  12. Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.

    Science.gov (United States)

    Fihlman, Mari; Hemmilä, Tuija; Hagelberg, Nora M; Kuusniemi, Kristiina; Backman, Janne T; Laitila, Jouko; Laine, Kari; Neuvonen, Pertti J; Olkkola, Klaus T; Saari, Teijo I

    2016-11-01

    This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine. We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured. Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC 0-∞ ) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance.

  13. Acceptability, compliance, and adverse reactions when isoniazid, rifampin, and pyrazinamide are given as a combined formulation or separately during three-times-weekly antituberculosis chemotherapy.

    Science.gov (United States)

    1989-12-01

    In Hong Kong, 627 adult Chinese patients with newly diagnosed pulmonary tuberculosis received, for the first 2 months of chemotherapy, streptomycin together with isoniazid, rifampin, and pyrazinamide allocated at random to be given either as a combined formulation or separately. Each tablet of the combined formulation, which was designed for intermittent use, contained 125 mg of isoniazid, 100 mg of rifampin, and 375 mg of pyrazinamide. Patients weighing 42 kg or less received 5 tablets per dose, 43 to 57 kg, 6 tablets per dose, and 58 kg or more, 7 tablets per dose. The dosage of each drug was very similar whether it was given combined or separately. During the 2 months, spontaneous complaints, the commonest of which were nausea and vomiting, were made by 38% of patients receiving the combined and 39% receiving the separate formulations; 1% compared with 5%, respectively, complained that the tablets or capsules were too many, too large, difficult to swallow or that they stuck in the throat (p less than 0.05), and 32% compared with 45% regularly brought their own drink (usually milk or fruit juice) to the clinic to help them swallow their medicament (p less than 0.01). Only 14% of patients in each group missed one or more doses through default. Reported adverse reactions were mainly trivial, 4% of patients receiving the combined and 7% receiving the separate formulations having the administration of one or more drugs terminated. Thus, the differences between the combined and separate formulations showed a small advantage to the combined formulation in terms of acceptability to patients.

  14. Ação do mononitrato-5 de isossorbida sublingual durante cinecoronariografia. Comparação com o uso de nitroglicerina sublingual Sublingual isosorbide-5 mononitrate during coronary arteriography. Comparison with sublingual nitroglycerin

    Directory of Open Access Journals (Sweden)

    Anellys E. L. C. Moreira

    1997-10-01

    Full Text Available OBJETIVO: Avaliar o efeito sublingual do mononitrato-5 de isossorbida (MN5IS e nitroglicerina (NTG sobre o diâmetro luminal de artérias coronárias epicárdicas, pressão arterial média e efeitos colaterais. MÉTODOS: Cinqüenta pacientes foram submetidos a cateterismo cardíaco e cinecoronariografia, na condição inicial e 5min após administração sublingual de MN5IS grupo A (GA ou NTG grupo B (GB. RESULTADOS: O diâmetro coronário de referência aumentou em ambos os grupos, sem significância estatística entre os mesmos. Nos GA e GB foram demonstrados uma diminuição (1,66mmHg e um aumento (0,79mmHg na pressão arterial média, respectivamente (p=0,123. Não foram observados efeitos colaterais com o uso destas drogas. CONCLUSÃO: MN5IS sublingual é uma alternativa à administração de NTG durante cinecoronariografia e representa uma alternativa terapêutica para o tratamento de doença cardíaca isquêmica.PURPOSE: To evaluate the effect of sublingual isosorbide-5 mononitrate (ISMN and nitroglycerin (NTG on luminal diameter of epicardial coronary arteries, mean arterial pressure and deleterious effects. METHODS: Fifty patients were submitted to cardiac catheterization and coronary arteriography, at baseline, and 5min after sublingual administration of ISMN, group A (GA or NTG, group B (GB. RESULTS: Reference vessel diameter increased in both groups, without statistical significance. In GA and GB, a decrease (1.66mmHg and an increase (0.79mmHg in mean arterial pressure, respectively, were demonstrated (p=0.123. There were no deleterious effects with the use of these drugs. CONCLUSION: Sublingual ISMN is an alternative to administration of NTG during coronary arteriography, and represents a therapeutic alternative to ischemic heart disease treatment.

  15. Development and evaluation of fixed dose bi therapy sublingual tablets for treatment stress hypertension and anxiety

    Directory of Open Access Journals (Sweden)

    Mohamed A El-Nabarawi

    2013-01-01

    Full Text Available Objective: A stress induced rise in the blood pressure. Some believe that patients with hypertension are characterized by a generalized state of increased anxiety. Aim: The purpose of this study is to prepare a fixed dose bi therapy using bisoprolol hemifumarate (BH as antihypertensive drug and buspirone hydrochloride (BuHCl as anxiolytic drug, which can be used to treat both diseases concomitantly. Using sublingual tablets is hopeful to improve the BuHCl poor oral bioavailability and to facilitate administration to patients experiencing problems with swallowing. Materials and Methods: A total of 5mg BH and 10mg BuHCl were selected based on compatibility study. A 3×22 full factorial design was adopted for the optimization of the tablets prepared by direct compression method. The effects of the filler type, the binder molecular weight, and the binder type were studied. The prepared formulae were evaluated according to their physical characters as hardness, friability, disintegration time (new modified method and in vivo disintegration time and wetting properties. In vitro drugs dissolute, permeation through the buccal mucosa and the effect of storage were analyzed by a new valid high pressure liquid chromatography (HPLC method. Bioavailability study of the selected formula study was carried out and followed by the clinical. Results: The optimized tablet formulation showed accepted average weight, hardness, wetting time, friability, content uniformity, disintegration time (less than 3 min. Maximum drug release could be achieved with in 10 min. In addition enhancing drug permeation through the buccal mucosa and, the maximum concentration of the drug that reached the blood was in the first 10 min which means a rapid onset of action and improved the extent of both drug′s absorption. Conclusion: The results revealed that sublingual (F6 tablets containing both drugs would maintain rapid onset of action, and increase bioavailability. BuHCl with BH

  16. Comparison of sublingual and vaginal misoprostol for second-trimester pregnancy terminations.

    Directory of Open Access Journals (Sweden)

    Forozan Milani

    2014-03-01

    Full Text Available Comparing sublingual and vaginal misoprostol in second trimester pregnancy termination.In this study 268 women at 12-24 weeks of gestation candidate for pregnancy termination were enrolled. Women were randomly divided in two groups. The first group received 400 µg sublingual misoprostol and vaginal placebo and the second group received 400 µg vaginal misoprostol and sublingual placebo every 4 hours for a maximum of five doses. The course of misoprostol was repeated if the women did not abort within 24 hours.The median induction-to-abortion interval was shorter in sublingual group (12/72 hours in sublingual and 14/67 hours in vaginal. There was no significant difference in the success rate at 24 and 48 hours and in side effects. The preference for the sublingual route of administration was higher.Both vaginal and sublingual misoprostol are effective for medical abortion in second trimester termination. But it appears from shorter induction interval in sublingual and higher acceptability that sublingual route is a better choice.

  17. Improving the controlled delivery formulations of caffeine in alginate hydrogel beads combined with pectin, carrageenan, chitosan and psyllium.

    Science.gov (United States)

    Belščak-Cvitanović, Ana; Komes, Draženka; Karlović, Sven; Djaković, Senka; Spoljarić, Igor; Mršić, Gordan; Ježek, Damir

    2015-01-15

    Alginate-based blends consisting of carrageenan, pectin, chitosan or psyllium husk powder were prepared for assessment of the best formulation aimed at encapsulation of caffeine. Alginate-pectin blend exhibited the lowest viscosity and provided the smallest beads. Alginate-psyllium husk blend was characterised with higher viscosity, yielding the largest bead size and the highest caffeine encapsulation efficiency (83.6%). The release kinetics of caffeine indicated that the porosity of alginate hydrogel was not reduced sufficiently to retard the diffusion of caffeine from the beads. Chitosan coated alginate beads provided the most retarded release of caffeine in water. Morphological characteristics of beads encapsulating caffeine were adversely affected by freeze drying. Bitterness intensity of caffeine-containing beads in water was the lowest for alginate-psyllium beads and chitosan coated alginate beads. Higher sodium alginate concentration (3%) for production of hydrogel beads in combination with psyllium or chitosan coating would present the most favourable carrier systems for immobilization of caffeine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Clinical safety and efficacy studies of a novel formulation combining 1.2% clindamycin phosphate and 0.025% tretinoin for the treatment of acne vulgaris.

    Science.gov (United States)

    Schlessinger, Joel; Menter, Alan; Gold, Michael; Leonardi, Craig; Eichenfield, Lawrence; Plott, R Todd; Leyden, James; Wortzman, Mitchell

    2007-06-01

    Clindamycin phosphate 1.2% and tretinoin 0.025% gel (CLIN/RA gel [ZIANA Gel]) is a novel topical combination agent approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older. A solution of clindamycin phosphate 1.2% combined with partially solubilized and crystalline tretinoin 0.025% suspended in an aqueous-based, alcohol-free gel formulation, CLIN/RA gel was studied in 2 randomized, vehicle-controlled trials involving more than 4,500 patients. Efficacy results from these studies showed that treatment with the combination significantly reduced lesion counts and improved patients' overall appearance to a greater extent than the individual components. Individual ingredients and the combination were well-tolerated. Among those treated with the combination formulation, discontinuation rates due to adverse events were 1% or less.

  19. Gum pigmentation: an unusual adverse effect of sublingual immunotherapy.

    Science.gov (United States)

    Goh, Anne; Chiang, Wen Chin; Kang, Liew Woei; Rao, Rajeshwar; Lim, Hwee Hoon; Chng, Chai Kiat

    2014-07-01

    Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is pigmentation of the gums which can occur anytime during the course of the immunotherapy. It resolves on stopping the immunotherapy and is likely due to a local inflammatory process occurring in the gums of these children. There is no associated pain or itching with the pigmentation. It can persist as long as the child is on the immunotherapy.

  20. Therapeutic Effects and Biomarkers in Sublingual Immunotherapy: A Review

    Directory of Open Access Journals (Sweden)

    Takashi Fujimura

    2012-01-01

    Full Text Available Immunotherapy is considered to be the only curative treatment for allergic diseases such as pollinosis, perennial rhinitis, asthma, and food allergy. The sublingual route is widely applied for immunotherapy for allergy, instead of the conventional administration by subcutaneous route. A recent meta-analysis of sublingual immunotherapy (SLIT has shown that this approach is safe, has positive clinical effects, and provides prolonged therapeutic effects after discontinuation of treatment. However, the mechanism of SLIT and associated biomarkers are not fully understood. Biomarkers that change after or during SLIT have been reported and may be useful for response monitoring or as prognostic indicators for SLIT. In this review, we focus on the safety, therapeutic effects, including prolonged effects after treatment, and new methods of SLIT. We also discuss response monitoring and prognostic biomarkers for SLIT. Finally, we discuss immunological mechanisms of SLIT with a focus on oral dendritic cells and facilitated antigen presentation.

  1. Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence

    OpenAIRE

    Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi

    2016-01-01

    Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient’s daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure...

  2. Formulation and evaluation of a topical niosomal gel containing a combination of benzoyl peroxide and tretinoin for antiacne activity

    Science.gov (United States)

    Gupta, Ankush; Singh, Sima; Kotla, Niranjan G; Webster, Thomas J

    2015-01-01

    A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of elastic vesicles (niosomes) which can be transported through the skin through channel-like structures. In this study, a combination of tretinoin (keratolytic agent) and benzoyl peroxide (BPO) (a potent antibacterial) was given by using niosomes as promising carriers for the effective treatment of acne by acting on a pathogenic site. In this section, niosomal gel formulation encapsulated drugs have been evaluated for in vitro, ex vivo, and in vivo, for their predetermined characteristics; and finally the stability of the niosome gel was tested at different temperature conditions for understanding of the storage conditions required for maintaining the quality of formulation attributes. The prepared niosome was found to be in the range of 531 nm with a zeta potential of −43 mV; the entrapment efficiencies of tretinoin (TRA) and BPO niosomes were found to be 96.25%±0.56% and 98.75%±1.25%, respectively. The permeated amount of TRA and BPO from the niosomal gel after 24 hours was calculated as 6.25±0.14 μg/cm2 and 5.04±0.014 μg/cm2, respectively. A comparative drug retention study in Wistar rat skin using cream, an alcoholic solution, and a niosomal gel showed 11.54 μg, 2.68 μg, and 15.54 μg amounts of TRA and 68.85 μg, 59.98 μg, and 143.78 μg amounts of BPO were retained in the layers of skin, respectively. In vivo studies of the niosomal gel and antiacne cream of TRA and BPO showed that the niosomal gel was more efficacious than the antiacne cream because niosomal gels with a 4.16-fold lower dose of BPO provided the same therapeutic index at targeted sites in comparison to the antiacne cream. PMID

  3. Use of formulated Trichoderma sp. Tri-1 in combination with reduced rates of chemical pesticide for control of Sclerotinia sclerotiorium on oilseed rape

    Science.gov (United States)

    Sustainable strategies for control of Sclerotinia sclerotiorum on oilseed rape are needed. Here we tested combinations of Trichoderma sp. Tri-1, formulated with oilseed rape seedcake and straw, with reduced application rates of the chemical pesticide Carbendazim for control of this pathogen on oils...

  4. Duration of immunity induced by an equine influenza and tetanus combination vaccine formulation adjuvanted with ISCOM-Matrix.

    Science.gov (United States)

    Heldens, J G M; Pouwels, H G W; Derks, C G G; Van de Zande, S M A; Hoeijmakers, M J H

    2010-10-08

    Equine influenza is a contagious disease caused by equine influenza virus which belongs to the orthomyxovirus family. Outbreaks of equine influenza cause severe economic loses to the horse industry and consequently horses in competition are required to be regularly vaccinated against equine influenza. Unlike the existing inactivated vaccines, Equilis Prequenza Te is the only one able to induce protection against clinical disease and virus excretion after a primary vaccination course consisting of two vaccine applications 4-6 weeks apart until the recommended time of the third vaccination. In this paper we describe the duration of immunity profile, tested in an experimental setting according to European legislation, of this inactivated equine influenza and tetanus combination vaccine. In addition to influenza antigen, the formulation contains a second generation ISCOM (the so called ISCOMatrix) as an adjuvant. The vaccine aims at the induction of protection from the primary vaccination course until the time of annual revaccination 12 months later, against challenge with a virulent equine influenza strain. The protection against A/equine/Kentucky/95 (H3N8) at the time of annual revaccination was evidenced by a significant reduction of clinical signs of influenza, a significant reduction of virus excretion and a significant reduction of fever. The effect of the annual revaccination on the duration of immunity against influenza and tetanus was also studied by serology. For tetanus, as a consequence of the 24 months duration of immunity, an alternating annual vaccination schedule consisting of Prequenza and Prequenza Te is proposed after the first three doses of Prequenza Te. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability.

    Science.gov (United States)

    De Caro, Viviana; Ajovalasit, Alessia; Sutera, Flavia Maria; Murgia, Denise; Sabatino, Maria Antonietta; Dispenza, Clelia

    2017-06-24

    Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young's Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m². FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application.

  6. Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability

    Directory of Open Access Journals (Sweden)

    Viviana De Caro

    2017-06-01

    Full Text Available Administered by an oral route, Furosemide (FUR, a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young’s Modulus, yield strength, and relative elongation of break percentage (EB% allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m2. FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application.

  7. Soy polysaccharide as a novel superdisintegrant in sildenafil citrate sublingual tablets: preparation, characterization, and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Hosny KM

    2015-01-01

    can be concluded that SC sublingual tablet is a promising formulation that results in higher solubility, faster dispersion and onset of action, higher release rate, and higher systemic bioavailability. Keywords: bioavailability, erectile dysfunction, onset of action, polyvinylpyrrolidone, Emcosoy

  8. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Khinchi, M S; Poulsen, Lars K.; Carat, F

    2004-01-01

    Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed.......Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed....

  9. Combined semi-empirical screening and design of experiments (DOE) approach to identify candidate formulations of a lyophilized live attenuated tetravalent viral vaccine candidate.

    Science.gov (United States)

    Patel, Ashaben; Erb, Steven M; Strange, Linda; Shukla, Ravi S; Kumru, Ozan S; Smith, Lee; Nelson, Paul; Joshi, Sangeeta B; Livengood, Jill A; Volkin, David B

    2017-05-12

    A combination experimental approach, utilizing semi-empirical excipient screening followed by statistical modeling using design of experiments (DOE), was undertaken to identify stabilizing candidate formulations for a lyophilized live attenuated Flavivirus vaccine candidate. Various potential pharmaceutical compounds used in either marketed or investigative live attenuated viral vaccine formulations were first identified. The ability of additives from different categories of excipients, either alone or in combination, were then evaluated for their ability to stabilize virus against freeze-thaw, freeze-drying, and accelerated storage (25°C) stresses by measuring infectious virus titer. An exploratory data analysis and predictive DOE modeling approach was subsequently undertaken to gain a better understanding of the interplay between the key excipients and stability of virus as well as to determine which combinations were interacting to improve virus stability. The lead excipient combinations were identified and tested for stabilizing effects using a tetravalent mixture of viruses in accelerated and real time (2-8°C) stability studies. This work demonstrates the utility of combining semi-empirical excipient screening and DOE experimental design strategies in the formulation development of lyophilized live attenuated viral vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. In vitro antioxidant, collagenase inhibition, and in vivo anti-wrinkle effects of combined formulation containing Punica granatum, Ginkgo biloba, Ficus carica, and Morus alba fruits extract

    Directory of Open Access Journals (Sweden)

    Ghimeray AK

    2015-07-01

    Full Text Available Amal Kumar Ghimeray,1 Un Sun Jung,1,2 Ha Youn Lee,1 Young Hoon Kim,1 Eun Kyung Ryu,1 Moon Sik Chang11R&D Center, Natural Solution Co., Ltd, Gojan-dong, Namdong-gu, Incheon, Republic of Korea; 2Department of Horticultural Biotechnology, Kyung Hee University, Yongin, Republic of KoreaBackground: In phytotherapy, the therapeutic potential is based on the combined action of different herbal drugs. Our objective was to evaluate the antioxidant, anti-collagenase (in vitro, and anti-wrinkle (in vivo effect of combined formulation containing Ginkgo biloba, Punica granatum, Ficus carica, and Morus alba fruits extract.Methods: Antioxidant evaluation was based on the scavenging activity of free radicals (1,1-diphenyl-2-picrylhydrazyl, H2O2, and O2- and the anti-collagenase activity was based on the reduction of collagenase enzyme in vitro. In an in vivo study, 21 female subjects were examined in a placebo-controlled trail. Facial wrinkle, especially the crow's feet region of eyes, was treated with topical formulated 2% cream for 56 days and compared with the placebo.Results: In the in vitro study, the combination of fruits extract showed a higher antioxidant activity which was comparable with the positive standard (ascorbic acid, butylated hydroxyanisole, and Trolox. The data also showed a dose-dependent inhibition of collagenase. In the in vivo study, treatment with 2% formulated cream for 56 days significantly reduced the percentage of wrinkle depth, length, and area with 11.5, 10.07, and 29.55, respectively.Conclusion: The combined formulation of fruit extracts showed excellent antioxidative and anti-collagenase activity as well as a significant effect on anti-wrinkle activity on human skin.Keywords: antioxidant, anti-collagenase, anti-wrinkle, fruits, topical formulation

  11. Development of nanoparticle based delivery systems for sublingual immunotherapy

    DEFF Research Database (Denmark)

    Alija, Hava; Rask, Carola; Brimnes, Jens

    The prevalence of IgE mediated allergic diseases is increasing dramatically in industrialized countries. Sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficacious treatment for IgE mediated allergic diseases, but requires protracted treatment duration. Even though SLIT...... is considered to have a better safety profile than subcutaneous immunotherapy, SLIT can still cause adverse events requiring clinical supervision for the first administration. Optimization of SLIT, by reducing the administration dose and treatment duration, would improve safety profile. For this purpose...

  12. Improvement of a dry formulation of Pseudomonas fluorescens EPS62e for fire blight disease biocontrol by combination of culture osmoadaptation with a freeze-drying lyoprotectant.

    Science.gov (United States)

    Cabrefiga, J; Francés, J; Montesinos, E; Bonaterra, A

    2014-10-01

    To study the effect of lyoprotectants and osmoadaptation on viability of Pseudomonas fluorescens EPS62e during freeze-drying and storage and to evaluate the formulation in terms of efficacy in biocontrol and fitness on pear flowers. A wettable powder formulation of a biocontrol agent of fire blight was optimized by means of lyoprotectants and culture osmoadaptation. Freeze-drying was used to obtain dehydrated cells, and the best viability (70% of survival) was obtained using lactose as lyoprotectant. Survival during lyophilization was additionally improved using physiological adaptation of cells during cultivation under salt-amended medium (osmoadaptation). The procedure increased the survival of cells after freeze-drying attaining viability values close to a 100% in the lactose-formulated product (3 × 10(11) CFU g(-1) ), and through the storage period of 1 year at 4°C. The dry formulation showed also an improved biocontrol efficacy and survival of EPS62e on pear flowers under low relative humidity conditions. Cell viability after freeze-drying was improved using lactose as lyoprotectant combined with a procedure of osmoadaptation during cultivation. The powder-formulated product remained active for 12 months and retained biocontrol levels similar to that of fresh cells. The formulation showed an improved survival of EPS62e on flowers and an increase of the efficacy of biocontrol of fire blight at low relative humidity. The results have a potential value for commercial application in biocontrol agents not only of fire blight but also of other plant diseases. © 2014 The Society for Applied Microbiology.

  13. A meta-analysis of sublingual allergen immunotherapy and pharmacotherapy in pollen-induced seasonal allergic rhinoconjunctivitis.

    Science.gov (United States)

    Devillier, Philippe; Dreyfus, Jean-François; Demoly, Pascal; Calderón, Moisés A

    2014-05-01

    The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible. We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo. Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast. In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact

  14. Development of a sublingual allergy vaccine for grass pollinosis

    Directory of Open Access Journals (Sweden)

    Franco Frati

    2010-06-01

    Full Text Available Franco Frati1,2, Silvia Scurati1, Paola Puccinelli1, Marie David3, Cecile Hilaire4, Maurizio Capecce4, Francesco Marcucci2, Cristoforo Incorvaia51Medical and Scientific Department, Stallergenes, Milan, Italy; 2University Department of Medical and Surgical Specialties and Public Health, Perugia, Italy; 3Laboratoire Stallergenes, Antony, France; 4Marketing Department, Stallergenes, Milan, Italy; 5Allergy/Pulmonary Rehabilitation Unit, ICP Hospital, Milan, ItalyAbstract: Grass pollen is a very common cause of allergic rhinitis and asthma. The only treatment targeting the underlying causes of allergy is immunotherapy (IT. Sublingual immunotherapy (SLIT has been introduced to solve the problem of systemic reactions to subcutaneous IT (SCIT. This article evaluates the characteristics of the allergen extract, Staloral, in terms of practical administration, effectiveness, safety, and mechanism of action. Efficacy data were obtained from double-blind, placebo-controlled studies using Staloral in patients sensitized to grass pollen, while practical administration, cost-effectiveness, and mechanism of action data were provided by well designed studies. The efficacy and safety of Staloral, as demonstrated by review of published studies which used doses up to 1125 times those administered with SCIT, shows that this allergen extract has optimal characteristics for treating patients with seasonal allergies due to grass pollens. The main mechanism of action is the interaction between dendritic cells of the oral mucosa and the subsequent tolerance induced in T-cells.Keywords: allergen extracts, high-dose, efficacy, safety, sublingual immunotherapy

  15. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp®) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions...... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...... of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus...

  16. Concurrent Spontaneous Sublingual and Intramural Small Bowel Hematoma due to Warfarin Use

    Directory of Open Access Journals (Sweden)

    Gül Pamukçu Günaydın

    2015-01-01

    Full Text Available Introduction. We present a case of concurrent spontaneous sublingual and intramural small bowel hematoma due to warfarin anticoagulation. Case. A 71-year-old man presented to the emergency department complaining of a swollen, painful tongue. He was on warfarin therapy. Physical examination revealed sublingual hematoma. His international normalized ratio was 11.9. The computed tomography scan of the neck demonstrated sublingual hematoma. He was admitted to emergency department observation unit, monitored closely; anticoagulation was reversed with fresh frozen plasma and vitamin K. 26 hours after his arrival to the emergency department, his abdominal pain and melena started. His abdomen tomography demonstrated intestinal submucosal hemorrhage in the ileum. He was admitted to surgical floor, monitored closely, and discharged on day 4. Conclusion. Since the patient did not have airway compromise holding anticoagulant, reversing anticoagulation, close monitoring and observation were enough for management of both sublingual and spontaneous intramural small bowel hematoma.

  17. Parotid and submandibular/sublingual salivary flow during high dose radiotherapy

    NARCIS (Netherlands)

    Burlage, FR; Coppes, RP; Meertens, H; Stokman, MA; Vissink, A

    2001-01-01

    It was studied whether differences in acute radiosensitivity exist between parotid and submandibular/sublingual glands. The results revealed that salivary flow rates decreased dramatically during the first 2 weeks of radiotherapy. Neither recovery nor significant differences were observed between

  18. Critical appraisal of the clinical utility of sublingual immunotherapy in allergy

    Directory of Open Access Journals (Sweden)

    S. Aissa

    2016-12-01

    We performed a literature review in order to remind the mechanisms of action and to demonstrate efficacy and tolerability of the sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma and its impact on the quality of life.

  19. Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography : a Systematic Review

    NARCIS (Netherlands)

    Takx, Richard A. P.; Suchá, D.; Park, Jakob; Leiner, Tim; Hoffmann, Udo

    2015-01-01

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic

  20. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis

    NARCIS (Netherlands)

    Dahl, Ronald; Kapp, Alexander; Colombo, Giselda; deMonchy, Jan G. R.; Rak, Sabina; Emminger, Waltraud; Rivas, Montserrat Fernandez; Ribel, Mette; Durham, Stephen R.

    Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking.

  1. effect of pre-operative sub-lingual misoprostol versus intravenous ...

    African Journals Online (AJOL)

    2012-09-09

    Sep 9, 2012 ... EFFECT OF PRE-OPERATIVE SUB-LINGUAL MISOPROSTOL VERSUS INTRAVENOUS OXYTOCIN ON CAESAREAN. OPERATION BLOOD LOSS ... infusion of oxytocin in reducing blood loss at Caesarean section operation. However, occurrence of ..... WHO Reproductive Health Library; Geneva: World.

  2. Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a phase-1 study

    DEFF Research Database (Denmark)

    Larsen, T H; Poulsen, Lars K.; Melac, M

    2006-01-01

    A single-centre, randomized, double-blind, placebo-controlled study. Aims: To compare the safety and tolerability of four different sublingual immunotherapy (SLIT) regimes in grass pollen allergic rhinitis....

  3. COMPARISON OF SUBLINGUAL THERAPEUTIC VACCINE WITH ANTIBIOTICS FOR THE PROPHYLAXIS OF RECURRENT URINARY TRACT INFECTIONS

    OpenAIRE

    María Fernanda Lorenzo-Gómez; María Fernanda Lorenzo-Gómez; María Fernanda Lorenzo-Gómez; Bárbara ePadilla-Fernández; María Begoña García-Cenador; Álvaro Julio Virseda Rodríguez; Álvaro Julio Virseda Rodríguez; Isidoro eMartín-García; Alfonso eSánchez-Escudero; Manuel José Vicente-Arroyo; José Antonio Mirón-Canelo

    2015-01-01

    Objective: To evaluate the clinical impact of the prophylactic treatment with sublingual immunostimulation in the prevention of recurrent urinary tract infections (rUTIs) compared with the use of antibiotics.Material and Methods: Retrospective cohort study evaluating the clinical records of 669 women with rUTIs; 339 had a 6-month prophylaxis with antibiotics and 360 had a 3-month prophylaxis with a sublingual bacterial preparation (MV 140-Uromune®). The time after the prophylaxis-period until...

  4. Comparison of sublingual therapeutic vaccine with antibiotics for the prophylaxis of recurrent urinary tract infections

    OpenAIRE

    Lorenzo-G?mez, Mar?a F.; Padilla-Fern?ndez, B?rbara; Garc?a-Cenador, Mar?a B.; Virseda-Rodr?guez, ?lvaro J.; Mart?n-Garc?a, Isidoro; S?nchez-Escudero, Alfonso; Vicente-Arroyo, Manuel J.; Mir?n-Canelo, Jos? A.

    2015-01-01

    Objective: To compare the clinical impact of a prophylactic treatment with sublingual immunostimulation in the prevention of recurrent urinary tract infections (rUTIs) with the use of antibiotics. Material and Methods: Retrospective cohort study evaluating the medical records of 669 women with rUTIs; 339 had a 6-month prophylaxis with antibiotics and 360 a 3-month prophylaxis with a sublingual bacterial preparation (MV 140-Uromune®). The time frame after the prophylaxis-period until the ap...

  5. Two-stage in vitro digestibility assay, a tool for formulating non-starch polysaccharide degrading enzyme combinations for commonly used feed ingredients of poultry rations

    Directory of Open Access Journals (Sweden)

    Y. Ramana Reddy

    2013-05-01

    Full Text Available Aim: An attempt was made to assess the effect of pure enzyme combinations with the objective of formulating customized enzyme mixtures based on sugar release when subjected to two-stage in vitro digestion assay. Materials and Methods: A two-stage in vitro digestibility assay was carried out for commonly used feed ingredients for poultry viz., maize, soy bean meal, sunflower cake, and de-oiled rice bran supplemented with three concentrations of xylanase (5000; 7500 and 10000 IU/kg, cellulase (50; 100 and 400 IU/kg and â-D-glucanase (100; 200 and 400 IU/kg were used to formulate various NSP enzymes combinations. In total 27 NSP enzyme combinations (3x3x3 were formulated and the sugar released due to NSP digestion was quantified by phenol sulphuric acid method. Results: The total sugar release was significantly (P<0.05 higher with supplementation of various enzymes combinations for maize, sunflower cake and de-oiled rice bran where as no significant (P<0.05 interaction of various NSP enzymes combinations was observed for soy bean meal. The NSP digestibility was highest in combination (xylanase-5000, cellulase-50 and â-D-glucanase-400 IU/kg, (xylanase-10000, cellulase-50 and â-D-glucanase-200 IU/kg and (xylanase-7500, cellulase- 100 and â-D-glucanase-100 IU/kg for maize, sunflower cake and de-oiled rice bran respectively. In case of sunflower cake, significant (P<0.01 three way interaction was observed among the xylanase, cellulose, and â-D-glucanase enzymes and the two-way interactions between the enzymes were also significant (P<0.01. Conclusion: It is concluded that 'n' number of non-starch Polysaccharide enzymes combinations can be screened for their efficiency to digest non-starch Polysaccharides present in various feed ingredients commonly used in poultry rations by employing two-stage in vitro digestibility assay as a tool. [Vet World 2013; 6(8.000: 525-529

  6. Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence.

    Science.gov (United States)

    Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi

    2016-02-08

    Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient's daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness.

  7. Subcutaneous and Sublingual Immunotherapy in Allergic Asthma in Children

    Directory of Open Access Journals (Sweden)

    Sophia Tsabouri

    2017-04-01

    Full Text Available This review presents up-to-date understanding of immunotherapy in the treatment of children with allergic asthma. The principal types of allergen immunotherapy (AIT are subcutaneous immunotherapy (SCIT and sublingual immunotherapy (SLIT. Both of them are indicated for patients with allergic rhinitis and/or asthma, who have evidence of clinically relevant allergen-specific IgE, and significant symptoms despite reasonable avoidance measures and/or maximal medical therapy. Studies have shown a significant decrease in asthma symptom scores and in the use of rescue medication, and a preventive effect on asthma onset. Although the safety profile of SLIT appears to be better than SCIT, the results of some studies and meta-analyses suggest that the efficacy of SCIT is better and that SCIT has an earlier onset than SLIT in children with allergic asthma. Severe, not controlled asthma, and medical error were the most frequent causes of SCIT-induced adverse events.

  8. Serum IL-9 levels and sublingual immunotherapy: preliminary report.

    Science.gov (United States)

    Ciprandi, G; De Amici, M; Marseglia, G L

    2011-01-01

    Th9 is a new T cell subset characterized by IL-9 production. It has been reported that serum IL-9 levels are related with symptom severity in patients with allergic rhinitis (AR). This study is aimed at investigating whether serum IL-9 may be modulated by sublingual immunotherapy (SLIT) in patients with persistent AR due to Parietaria allergy. Twenty-one AR patients (9 males, median age 41 years) successfully treated with SLIT and 52 AR patients (25 males, median age 34 years) treated only with drugs were evaluated during the pollen season. Serum IL-9 was dosed in all patients. SLIT-treated patients showed significantly lower serum IL-9 levels than untreated AR patients (p <0.0001). In conclusion, this preliminary study shows that a single pre-seasonal SLIT course might modulate serum IL-9.

  9. Adenoid cystic carcinoma of the sublingual gland: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ji Young [Dept. of Oral and Maxillofacial Surgery, School of Medicine, Jeju National University, Jeju (Korea, Republic of)

    2016-12-15

    Adenoid cystic carcinoma (ACC) of the sublingual gland is an extremely rare neoplasm. The clinicopathological characteristics of ACC are slow-growing swelling with or without ulceration, perineural spread, local recurrence, and distant metastasis. This report describes a 58-year-old male who had a slowly growing swelling without ulceration on the right side of the mouth floor that had been present for 1 month. In a radiological examination, the mass showed multilocular cystic features and no bony or tongue muscle invasion. No enlarged cervical lymph nodes were detected. Excisional biopsy and histological analysis showed that the lesion was ACC. In addition to reporting a rare case of ACC, this report also discusses the differential diagnosis and treatment of ACC with a review of the relevant literature.

  10. Treating allergic rhinitis by sublingual immunotherapy: a review

    Directory of Open Access Journals (Sweden)

    Cristoforo Incorvaia

    2012-06-01

    Full Text Available OBJECTIVE: Allergic rhinitis (AR is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT, but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years.

  11. Sublingual immunotherapy for allergic rhinitis: where are we now?

    Science.gov (United States)

    Incorvaia, Cristoforo; Mauro, Marina; Ridolo, Erminia

    2015-01-01

    Sublingual immunotherapy (SLIT) was introduced in the 1980s as a safer option to subcutaneous immunotherapy and in the latest decade achieved significant advances. Its efficacy in allergic rhinitis is supported by a number of meta-analyses. The development of SLIT preparations in tablets to fulfill the requirements of regulatory agencies for quality of allergen extracts made available optimal products for grass-pollen-induced allergic rhinitis. Preparations of other allergens based on the same production methods are currently in progress. A notable outcome of SLIT, that is shared with subcutaneous immunotherapy, is the evident cost-effectiveness, showing significant cost savings as early as 3 months from starting the treatment, that become as high as 80% compared with drug treatment in the ensuing years.

  12. Histoanatomical study of the Sublingual Salivary Gland in the Camel

    Directory of Open Access Journals (Sweden)

    M.a Ebrahimi

    2008-02-01

    Full Text Available The heads of ten adult camels were used in this study. Following skin removal, the length, width and thickness of the gland was measured by ruler and caliper. Dye injection was used to distinguish the sublingual duct papilla and 1cm sections from the gland were removed and fixed to prepare histologic sections stained with H & E for microscopic studies. The long, ribbon like and lobulated monostomatic part of the gland is situated underneath the tongue alongside the hypoglossus muscle. This part of the gland begins from the mandibular symphysis and is continued caudally to near the root of the tongue. The average length, width and thickness of this part were 15.2±0.02, 2.2±0.03 and 0.5±0.05 cm respectively. The polystomatic part was observed as scattered and lobulated near the submucosa and in front of the monostomatic part with decreasing concentration caudally. The average size of these fragments was approximately 0.5±0.02 cm. The overall appearance of the gland was lobulated with a pink colour. The monostomatic part has a single duct entering the sublingual caruncle. The minute polystomatic ducts open into the depressions alongside the tongue inside the oral cavity. These ducts are numerous. Histologically, the gland is surrounded by a capsule of dense connective tissue. Trabcules from the capsule penetrate the gland and divide it into lobules. Loose connective tissue makes up the framework of the gland and there are tubulo-acinus glands in the spaces of this framework. Approximately 95% of the secretory cells of this gland consist of mucous secreting cells. Myoepithelial cells are seen on the external surface of the secretory cells and also alongside the connecting ducts.

  13. Monitoring Microcirculatory Blood Flow with a New Sublingual Tonometer in a Porcine Model of Hemorrhagic Shock

    Directory of Open Access Journals (Sweden)

    Péter Palágyi

    2015-01-01

    Full Text Available Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (n=9 and shock groups (n=27. Hemorrhagic shock was induced by reducing mean arterial pressure (MAP to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60–180 min. Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV and capillary perfusion rate (CPR were assessed by orthogonal polarization spectral (OPS imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap (PSLCO2 gap, which significantly improved during the 120 min resuscitation phase. There was significant correlation between PSLCO2 gap and sublingual RBCV (r=-0.65, p<0.0001, CPR (r=-0.64, p<0.0001, central venous oxygen saturation (r=-0.50, p<0.0001, and central venous-to-arterial PCO2 difference (r=0.62, p<0.0001. This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock.

  14. Clinical benefits of treatment with SQ house dust mite sublingual tablet in house dust mite allergic rhinitis.

    Science.gov (United States)

    Demoly, P; Kleine-Tebbe, J; Rehm, D

    2017-10-01

    Treatment with SQ (standardised quality) house dust mite sublingual tablet for 1 year resulted in a decreased probability of having an allergic rhinitis (AR) exacerbation day (from 11% [placebo] to 5% [SQ house dust mite sublingual tablet]) and an increased probability of having a mild AR day (from 16% [placebo] to 34% [SQ house dust mite sublingual tablet]). © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  15. Pharmacokinetics and relative bioavailability of fixed-dose combination of clopidogrel and aspirin versus coadministration of individual formulations in healthy Korean men.

    Science.gov (United States)

    Choi, Hyang-Ki; Ghim, Jong-Lyul; Shon, Jihong; Choi, Young-Kyung; Jung, Jin Ah

    2016-01-01

    Simultaneous prescription of clopidogrel and low-dose aspirin is recommended for the treatment of acute coronary syndrome because of improvements in efficacy and patient compliance. In this study, the pharmacokinetics of a fixed-dose combination (FDC) of clopidogrel and aspirin was compared with coadministration of individual formulations to clarify the equivalence of the FDC. This was a randomized, open-label, two-period, two-treatment, crossover study in healthy Korean men aged 20-55 years. Subjects received two FDC capsules of clopidogrel/aspirin 75/100 mg (test) or two tablets of clopidogrel 75 mg and two capsules of aspirin 100 mg (reference) with a 14-day washout period. Plasma concentrations of clopidogrel, aspirin, and salicylic acid were measured using validated ultraperformance liquid chromatography-tandem mass spectrometry. Bioequivalence was assessed by analysis of variance and calculation of the 90% confidence intervals (CIs) of the ratios of the geometric means (GMRs) for AUClast and Cmax for clopidogrel and aspirin. Sixty healthy subjects were enrolled, and 53 completed the study. Clopidogrel, aspirin, and salicylic acid showed similar absorption profiles and no significant differences in Cmax, AUClast, and Tmax between FDC administration and coadministration of individual formulations. The GMRs (90% CI) for the Cmax and AUClast of clopidogrel were 1.08 (0.95, 1.23) and 0.93 (0.84, 1.03), respectively. The GMRs (90% CI) for the Cmax and AUClast of aspirin were 0.98 (0.84, 1.13) and 0.98 (0.93, 1.04), respectively. Both treatments were well tolerated in the study subjects. The FDC of clopidogrel and aspirin was bioequivalent to coadministration of each individual formulation. The FDC capsule exhibited similar safety and tolerability profiles to the individual formulations. Therefore, clopidogrel/aspirin 75 mg/100 mg FDC capsules can be prescribed to improve patient compliance.

  16. Effect of preload alternations on a new Doppler echocardiographic index of combined systolic and diastolic performance

    DEFF Research Database (Denmark)

    Møller, J E; Poulsen, S H; Egstrup, K

    1999-01-01

    The objective of the study was to assess the effect of preload alternations on a nongeometric Doppler index of combined systolic and diastolic myocardial performance (MPI). Doppler echocardiography was performed during Valsalva maneuver, passive leg lifting, and after sublingual administration...

  17. Sublingual immunization with the phosphate-binding-protein (PstS) reduces oral colonization by Streptococcus mutans.

    Science.gov (United States)

    Ferreira, E L; Batista, M T; Cavalcante, R C M; Pegos, V R; Passos, H M; Silva, D A; Balan, A; Ferreira, L C S; Ferreira, R C C

    2016-10-01

    Bacterial ATP-binding cassette (ABC) transporters play a crucial role in the physiology and pathogenicity of different bacterial species. Components of ABC transporters have also been tested as target antigens for the development of vaccines against different bacterial species, such as those belonging to the Streptococcus genus. Streptococcus mutans is the etiological agent of dental caries, and previous studies have demonstrated that deletion of the gene encoding PstS, the substrate-binding component of the phosphate uptake system (Pst), reduced the adherence of the bacteria to abiotic surfaces. In the current study, we generated a recombinant form of the S. mutans PstS protein (rPstS) with preserved structural features, and we evaluated the induction of antibody responses in mice after sublingual mucosal immunization with a formulation containing the recombinant protein and an adjuvant derived from the heat-labile toxin from enterotoxigenic Escherichia coli strains. Mice immunized with rPstS exhibited systemic and secreted antibody responses, measured by the number of immunoglobulin A-secreting cells in draining lymph nodes. Serum antibodies raised in mice immunized with rPstS interfered with the adhesion of bacteria to the oral cavity of naive mice challenged with S. mutans. Similarly, mice actively immunized with rPstS were partially protected from oral colonization after challenge with the S. mutans NG8 strain. Therefore, our results indicate that S. mutans PstS is a potential target antigen capable of inducing specific and protective antibody responses after sublingual administration. Overall, these observations raise interesting perspectives for the development of vaccines to prevent dental caries. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Assay of effervescent tablets by near-infrared spectroscopy in transmittance and reflectance mode: acetylsalicylic acid in mono and combination formulations.

    Science.gov (United States)

    Merckle, P; Kovar, K A

    1998-07-01

    Near-infrared spectroscopy (NIRS) was used to determine acetylsalicylic acid (ASA) in three different effervescent tablet formulations. The nominal ASA concentrations were 14.9% in the single substance formulation (ASA Mono), 17.4% in the combination with ascorbic acid (ASA + C) and 8.7% in the combination with paracetamol and ascorbic acid (ASA Combi). In each case the tablet matrix was composed of seven excipients typical of effervescent tablets. All three formulations were measured as intact tablets in diffuse transmittance and reflectance and as powdered tablets in diffuse reflectance. Calibration was carried out by partial least square (PLS) regression of second derivative spectra. High-performance liquid chromatography (HPLC) was used as the reference method. The relative standard errors of calibration (RSEC) achieved for the three NIR methods were between 1.20 and 2.01% for ASA Mono, between 1.91 and 2.21% for ASA + C and between 2.41 and 4.50% for ASA Combi. The results obtained in transmittance mode were comparable with those obtained in reflectance mode, which is normally used in NIRS. In the test sets of ASA Mono and ASA + C relative root mean square (RRMS) values between 2.21 and 3.13% were obtained. The three NIR methods applied are thus suitable for the quantitative determination of ASA in effervescent tablets and have the advantage over HPLC of being rapid and simply carried out with little sample preparation; they are nondestructive and do not require any environmentally harmful reagents.

  19. Analysis of Piroxicam in Pharmaceutical Formulation and Human Urine by Dispersive Liquid–Liquid Microextraction Combined with Spectrophotometry

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    Nakisa Seyyedeh Tutunchi

    2013-02-01

    Full Text Available Purpose: Piroxicam, is non–steroidal anti–inflammatory and analgesic agent, which is widely used in the treatment of patients with rheumatologic disorders. A new analytical approach based on the dispersive liquid–liquid microextraction (DLLME has been developed for the extraction and determination of PX in pharmaceutical preparation and human urine. Methods: From the PX standard solution or solutions prepared from real samples, aliquot volumes were pipetted into centrifuge tubes and mixed with acetate buffer at pH 3.0 and NaCl solution. The contents were subjected to the DLLME, so 700 μL of methanol containing 70 μL of chloroform was injected rapidly into a sample solution. A cloudy solution was rapidly produced and the PX extracted into dispersed fine droplets. The mixture was centrifuged, thus these fine droplets of chloroform were settled. The supernatant aqueous phase was readily decanted, then the remained organic phase was diluted with ethanol and the absorbance measured at 355 ± 3 nm against a reagent blank. Results: The main factors affecting the extraction efficiency such as pH, extraction and disperser solvent types and etc. were studied and optimized systematically. Under optimized conditions, the calibration graphs were linear over the range of 0.2 to 4.8 μg/mL. The limit of detection and relative standard deviation were found to be 0.058 μg/mL and 2.83%, respectively. Relative recoveries in the spiked samples ranged from 97 to 110%. Conclusion: Using the developed method PX can be analyzed in pharmaceutical formulation and human urine sample in a simpler, cheaper and more rapid manner.

  20. Pharmacokinetic non-interaction analysis in a fixed-dose formulation in combination of atorvastatin and ezetimibe

    Directory of Open Access Journals (Sweden)

    Omar ePatiño-Rodríguez

    2014-11-01

    Full Text Available Recent clinical research has shown that atorvastatin in combination with cholesterol absorption inhibitor ezetimibe significantly reduces LDL-C level in patients with hypercholesterolemia, showing a superior lipid-lowering efficacy compared to statin alone. With no information currently available on the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the influence of ezetimibe on atorvastatin and conversely when the two drugs were coadministered. The purpose of this study was to investigate the presence of differences in the pharmacokinetic profiles of capsules containing atorvastatin 80 mg, ezetimibe 10 mg or the combination of both 80/10 mg administered to healthy Mexican volunteers. This was a randomized, three-period, six-sequences crossover study. 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by non-compartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC and maximum plasma drug concentration (Cmax were measured for each drug alone or together and tested for bioequivalence-based hypothesis. The estimation computed (90% confidence intervals for AUC and Cmax, were 96.04% (85.88%–107.42% and 97.04% (82.36%–114.35%, respectively for atorvastatin-ezetimibe combination versus atorvastatin alone, while 84.42% (77.19%–92.32% and 95.60% (82.43%–110.88%, respectively, for atorvastatin-ezetimibe combination versus ezetimibe alone were estimated. These results suggest that atorvastatin and ezetimibe have no relevant pharmacokinetic drug-drug interaction.

  1. Current issues on sublingual allergen-specific immunotherapy in children with asthma and allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Živković Zorica

    2016-01-01

    Full Text Available In 1993 the European Academy of Allergy and Clinical Immunology was the first official organization to recognize that sublingual administration could be “promising route” for allergic desensitization. A few years later, the World Health Organization recommended this therapy as “a viable alternative to the injection route in adults.” The first meta-analysis showed sublingual allergen specific immunotherapy (SLIT effectiveness for allergic rhinitis and another study showed SLIT can actually help prevent the development of asthma both in adults and in children. The main goal of this review article is to present insight into the most up-to-date understanding of the clinical efficacy and safety of immunotherapy in the treatment of pediatric patients with allergic rhinitis and asthma. A literature review was performed on PubMed from 1990 to 2015 using the terms “asthma,” “allergic rhinitis,” “children,” “allergen specific immune therapy.” Evaluating data from double-blind placebo-controlled randomized clinical trials (DB-PC-RCTs, the clinical efficacy (assessed as the reduction of symptom score and the need of rescue medicament of SLIT for allergic rhinitis and allergic asthma, has been confirmed in various meta-analysis Outcomes such as rhinoconjunctivitis score and medication scores, combined scores, quality of life, days with severe symptoms, immunological endpoints, and safety parameters were all improved in the SLIT-tablet compared with placebo group. SLIT safety has been already proven in many DB-PC-RCTs and real-life settings. In accordance with all of the above mentioned, the goals for future trials and studies are the development of comprehensive guidelines for clinical practice on immunotherapy, embracing all the different potential participants. The importance of allergen immunotherapy is of special relevance in the pediatric age, when the plasticity and modulability of the immune system are maximal, and when

  2. The Formulation and Solution of the Multi-objective Optimization Problem for an Autonomous Electrohydraulic Servo Actuator with Combined Control

    Directory of Open Access Journals (Sweden)

    O. S. Nozhnin

    2017-01-01

    Full Text Available The rapid development of electrical engineering industries for aviation has resulted in a gradual transition to the autonomous electrohydraulic drives, among which an electro-hydrostatic drive is currently considered to be the most advanced. However, high requirements for dynamic parameters of modern unstable and low-stability aircrafts put restriction on implementation of electro-hydrostatic drives in the industry.A combined control hydraulic drive arisen from the electro-hydrostatic drive development solves the problem of low dynamic parameters. High dynamics for combined control is achieved through the use of double (throttle and electric power control with each of them being predominant depending on the input signal value.Due to small knowledge of the drive with combined control, the article proposes to use a multi-criterion optimization method in order to obtain optimal results in its development. This will allows an adequate estimate of drive performance for its comparison with analogues and a justification of the feasibility of further research as well.The article describes all the stages of multi-criteria optimization of the combined control drive using the LP-search method. Optimization is carried out taking into account the requirements for modern aircrafts. As criteria, were taken three values , which, in the authors' opinion, provide the most complete description of the entire drive quality (a drive power consumption in the "neutral", an efficiency of the hydraulic part of the drive in the mode of electric power control, a value of ITAE when driving with a small signal. As a result of optimization, the Pareto front was obtained in three coordinates, corresponding to effective solutions, after which a compromise between the criteria was found, and the optimal solution was chosen.The design solution of the combined control drive, obtained after optimization, meets all the requirements for modern aircrafts and has both the high power

  3. Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

    Directory of Open Access Journals (Sweden)

    Sachiko Fukui

    2017-03-01

    Full Text Available The purpose of this study was to develop an extended-release (ER matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS and hydroxypropylcellulose (HPC were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet. Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method, dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin. Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

  4. Morphology and morphometry of the human sublingual glands in mouth floor enlargements of edentulous patients

    Directory of Open Access Journals (Sweden)

    Josiane Costa Rodrigues de SA

    2013-12-01

    Full Text Available Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. Objective: The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Material and Methods: Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20 and edentulous cadavers (n=20. The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p0.05. Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043. The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05. CONCLUSION: The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements.

  5. Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography: a Systematic Review.

    Science.gov (United States)

    Takx, Richard A P; Suchá, Dominika; Park, Jakob; Leiner, Tim; Hoffmann, Udo

    2015-12-01

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Sublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes. • Sublingual nitroglycerin administration results in significant coronary artery dilatation. • Nitroglycerin increases the number of evaluable coronary branches. • Image quality is improved the most in smaller coronary branches. • Nitroglycerin increases the diagnostic accuracy of coronary CT angiography. • Most side effects are mild and do not require medical intervention.

  6. Salivary lactoferrin is transferred into the brain via the sublingual route.

    Science.gov (United States)

    Hayashi, Takashi; To, Masahiro; Saruta, Juri; Sato, Chikatoshi; Yamamoto, Yuko; Kondo, Yusuke; Shimizu, Tomoko; Kamata, Yohei; Tsukinoki, Keiichi

    2017-07-01

    Lactoferrin (LF) is produced by exocrine glands including salivary gland, and has various functions including infection defense. However, the transfer of LF from peripheral organs into the brain remains unclear. To clarify the kinetics of salivary LF (sLF), we investigated the consequences of sialoadenectomy and bovine LF (bLF) sublingual administration in rats. The salivary glands were removed from male Wistar rats, and we measured rat LF levels in the blood and brain at 1 week post-surgery. We also examined the transfer of LF into the organs of the rats after sublingual administration of bLF. Rat LF levels in the blood and brain were significantly reduced by sialoadenectomy. Sublingual bLF administration significantly increased bLF levels in the brain, which then decreased over time. These results indicate that LF is transferred from the sublingual mucosa to the brain, in which favorable effects of sLF on brain will be expected via the sublingual mucosa.

  7. Combined Atomistic Molecular Calculations and Experimental Investigations for the Architecture, Screening, Optimization, and Characterization of Pyrazinamide Containing Oral Film Formulations for Tuberculosis Management.

    Science.gov (United States)

    Adeleke, Oluwatoyin A; Monama, Nkwe O; Tsai, Pei-Chin; Sithole, Happy M; Michniak-Kohn, Bozena B

    2016-02-01

    semicrystalline in nature and displayed a dual phased ex vivo mucosal permeation pattern. In silico and in vitro physicomechanical quantities revealed OF 2's flexibility, robustness, and compressibility. OF 2 was most stable under controlled environmental humidity, pressure, and temperature conditions in silico and in vitro. OF 2 was potentially non-cytotoxic and biocompatible. Succinctly, this work demonstrated the applicability of a combination of atomistic molecular mechanics and dynamics calculations as well as experimental analyses to the fabrication, screening, optimization, and characterization of drug formulations. Lastly, the fabricated OF 2 formulation can function as a potential alternative for the effective loading and delivery of PYZ.

  8. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Bo [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Sun, Ding [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Department of Hepatobiliary Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Zhu, Qing-Feng [The Johns Hopkins University School of Medicine, Division of Gastrointestinal and Liver Pathology, Baltimore, MD, 21205 (United States); Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 (China); Yang, Xin-Rong [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Gao, Ya-Bo [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032 (China); Tang, Wei-Guo [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Fan, Jia [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 (China); Maitra, Anirban [The Sol Goldman Pancreatic Cancer Research Center, Departments of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); and others

    2015-12-25

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. - Highlights: • Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. • In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest. • NanoCurcumin and

  9. Cost-Utility of a Single-Injection Combined Corticosteroid-Hyaluronic Acid Formulation vs a 2-Injection Regimen of Sequential Corticosteroid and Hyaluronic Acid Injections.

    Science.gov (United States)

    Belzile, Etienne L; Deakon, Robert T; Vannabouathong, Christopher; Bhandari, Mohit; Lamontagne, Martin; McCormack, Robert

    2017-01-01

    Research has shown early and sustained relief with a combination therapy of a corticosteroid (CS) and hyaluronic acid (HA) in knee osteoarthritis (OA) patients. This can be administered via a single injection containing both products or as separate injections. The former may be more expensive when considering only product cost, but the latter incurs the additional costs and time of a second procedure. The purpose of this study was to compare the cost-utility of the single injection with the 2-injection regimen. The results of this analysis revealed that the single-injection formulation of a CS and HA may be cost-effective, assuming a willingness-to-pay of $50 000 per quality-adjusted life year gained, for symptomatic relief of OA symptoms. This treatment may also be more desirable to patients who find injections to be inconvenient or unpleasant.

  10. Selection of patients for sublingual versus subcutaneous immunotherapy.

    Science.gov (United States)

    Larenas Linnemann, Désirée E S; Blaiss, Michael S

    2014-01-01

    Allergen immunotherapy is the sole treatment for IgE-mediated allergic diseases directed at the underlying mechanism. The two widely accepted administration routes are sublingual (SLIT) and subcutaneous (SCIT). We reviewed how patients should best be selected for immunotherapy and how the optimal administration route can be defined. Before deciding SCIT or SLIT, appropriate selection of patients for allergen immunotherapy (AIT) is mandatory. To be eligible for AIT, subjects must have a clear medical history of allergic disease, with exacerbation of symptoms on exposure to one or more allergens and a corresponding positive skin or in vitro test. Then the route of administration should be based on: published evidence of clinical and immunologic efficacy (which varies per allergic disease and per allergen); mono- or multi-allergen immunotherapy, for SLIT multi-allergen immunotherapy was not effective; safety: adverse events with SLIT are more frequent, but less severe; and, costs and patient preferences, closely related to adherence issues. All these are discussed in the article.

  11. Local Side Effects of Sublingual and Oral Immunotherapy.

    Science.gov (United States)

    Passalacqua, Giovanni; Nowak-Węgrzyn, Anna; Canonica, Giorgio Walter

    Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Heterologous prime-boost strategy in non-human primates combining the infective dengue virus and a recombinant protein in a formulation suitable for human use.

    Science.gov (United States)

    Valdés, Iris; Hermida, Lisset; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Martín, Jorge; Bernardo, Lídice; López, Carlos; Niebla, Olivia; Menéndez, Tamara; Romero, Yaremis; Sánchez, Jorge; Guzmán, María G; Guillén, Gerardo

    2010-05-01

    The aim of the present work was to test the concept of the heterologous prime-boost strategy combining an infective dengue virus with a recombinant chimeric protein carrying domain III of the envelope protein. Two studies in monkeys, combining recombinant protein PD5 (domain III of the envelope protein from dengue-2 virus, fused to the protein carrier P64k) and the infective dengue virus in the same immunization schedules were carried out. Humoral and cell-mediated immunity were evaluated. In the first study, monkeys received four doses of the protein PD5 and were subsequently infected with one dose of dengue virus. Antibody response measured after virus inoculation was significantly higher compared to that in non-primed monkeys and comparable to that elicited after two doses of infective virus. In a second study, monkeys were infected with one dose of the virus and subsequently boosted with one dose of the recombinant protein, reaching high levels of neutralizing antibodies, which were still detectable 14 months after the last immunization. In addition, the cellular immune response was also recalled. The results obtained in the present work support the approach of heterologous prime-boosting, in either order prime or boost, combining the chimeric protein PD5 (formulated in alum-CPS-A) and an infective dengue virus. The latter could potentially be replaced by an attenuated vaccine candidate. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. A vaccine formulation combining rhoptry proteins NcROP40 and NcROP2 improves pup survival in a pregnant mouse model of neosporosis.

    Science.gov (United States)

    Pastor-Fernández, Iván; Arranz-Solís, David; Regidor-Cerrillo, Javier; Álvarez-García, Gema; Hemphill, Andrew; García-Culebras, Alicia; Cuevas-Martín, Carmen; Ortega-Mora, Luis M

    2015-01-30

    Currently there are no effective vaccines for the control of bovine neosporosis. During the last years several subunit vaccines based on immunodominant antigens and other proteins involved in adhesion, invasion and intracellular proliferation of Neospora caninum have been evaluated as targets for vaccine development in experimental mouse infection models. Among them, the rhoptry antigen NcROP2 and the immunodominant NcGRA7 protein have been assessed with varying results. Recent studies have shown that another rhoptry component, NcROP40, and NcNTPase, a putative dense granule antigen, exhibit higher expression levels in tachyzoites of virulent N. caninum isolates, suggesting that these could be potential vaccine candidates to limit the effects of infection. In the present work, the safety and efficacy of these recombinant antigens formulated in Quil-A adjuvant as monovalent vaccines or pair-wise combinations (rNcROP40+rNcROP2 and rNcGRA7+rNcNTPase) were evaluated in a pregnant mouse model of neosporosis. All the vaccine formulations elicited a specific immune response against their respective native proteins after immunization. Mice vaccinated with rNcROP40 and rNcROP2 alone or in combination produced the highest levels of IFN-γ and exhibited low parasite burdens and low IgG antibody levels after the challenge. In addition, most of the vaccine formulations were able to increase the median survival time in the offspring. However, pup survival only ensued in the groups vaccinated with rNcROP40+rNcROP2 (16.2%) and rNcROP2 (6.3%). Interestingly, vertical transmission was not observed in those survivor pups immunized with rNcROP40+rNcROP2, as shown by PCR analyses. These results show a partial protection against N. caninum infection after vaccination with rNcROP40+rNcROP2, suggesting a synergistic effect of the two recombinant rhoptry antigens. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Sharp tooth induced sublingual hematoma in a patient with elevated international normalized ratio

    Directory of Open Access Journals (Sweden)

    John Baliah

    2015-01-01

    Full Text Available Sublingual hematoma secondary to anticoagulation is a rare fatal condition. Hemorrhagic complications of warfarin are well-known. This particular case is unique because the patient was on warfarin for the past 2 years but did not develop the sublingual hematoma. However, a trauma by an attrited sharp cusp triggered the episode of the sublingual hematoma in this patient. Being a medical emergency, patient was promptly hospitalized in cardiac care unit and managed by medical team. The patient was transfused with 2 units of fresh frozen plasma and warfarin was temporarily stopped for 4 days. Alternate day regimen of warfarin was started after 4 days, and international normalized ratio dropped to 3. In dental management, enameloplasty of the mandibular first molar tooth was done to prevent trauma and ulcer development in the floor of the mouth. The hematoma resolved, and no new hematoma formation was observed for a period of 6 months.

  15. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma.

    Science.gov (United States)

    Hu, Bo; Sun, Ding; Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang; Zhu, Qing-Feng; Yang, Xin-Rong; Gao, Ya-Bo; Tang, Wei-Guo; Fan, Jia; Maitra, Anirban; Anders, Robert A; Xu, Yang

    2015-12-25

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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

  17. Impact of extrafine formulations of inhaled corticosteroids/long-acting beta-2 agonist combinations on patient-related outcomes in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Scichilone N

    2014-11-01

    Full Text Available Nicola Scichilone,1 Alida Benfante,1 Luca Morandi,2 Federico Bellini,2 Alberto Papi21Biomedical Department of Internal and Specialist Medicine, Section of Pulmonology, University of Palermo, Italy; 2Respiratory Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, ItalyAbstract: Asthma and chronic obstructive pulmonary disease (COPD are among the most common chronic diseases worldwide, characterized by a condition of variable degree of airway obstruction and chronic airway inflammation. A large body of evidence has demonstrated the importance of small airways as a pharmacological target in these clinical conditions. Despite a deeper understanding of the pathophysiological mechanisms, the epidemiological observations show that a significant proportion of asthmatic and COPD patients have a suboptimal (or lack of control of their diseases. Different factors could influence the effectiveness of inhaled treatment in chronic respiratory diseases: patient-related (eg, aging; disease-related (eg, comorbid conditions; and drug-related/formulation-related factors. The presence of multiple illnesses is common in the elderly patient as a result of two processes: the association between age and incidence of degenerative diseases; and the development over time of complications of the existing diseases. In addition, specific comorbidities may contribute to impair the ability to use inhalers, such as devices for efficient drug delivery in the respiratory system. The inability to reach and treat the peripheral airways may contribute to the lack of efficacy of inhaled treatments. The recent development of inhaled extrafine formulations allows a more uniform distribution of the inhaled treatment throughout the respiratory tree to include the peripheral airways. The beclomethasone/formoterol extrafine formulation is available for the treatment of asthma and COPD. Different biomarkers of peripheral airways are improved by beclomethasone

  18. Synergistic combination of antioxidants, silver nanoparticles and chitosan in a nanoparticle based formulation: Characterization and cytotoxic effect on MCF-7 breast cancer cell lines.

    Science.gov (United States)

    Nayak, Debasis; Minz, Aliva Prity; Ashe, Sarbani; Rauta, Pradipta Ranjan; Kumari, Manisha; Chopra, Pankaj; Nayak, Bismita

    2016-05-15

    Chitosan (Cs) is a biocompatible, biodegradable cationic polymer having the ability of targeted drug delivery. Vitamin E and C are not synthesized in our body thus, when encapsulated within a carrier system these vitamins in combination with/alone can be utilized for their anti-cancer potentials. The present investigation was conducted to develop a stable nanoparticle based formulation encapsulating antioxidants (Vitamin E, catechol) and silver nanoparticles synthesized from Hibiscus rosa-sinensis (HRS) petal extracts within a chitosan matrix. The prepared nanoformulations were characterized using Field emission scanning electron microscopy (Fe-SEM), X-ray diffraction (XRD) and Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR). They were further tested for their antioxidant potentials using DPPH assay, hydrogen peroxide scavenging assay, nitric oxide scavenging assay and ferrous antioxidant reducing potential assay. The nanoformulations were found to be highly hemocompatible and showed high encapsulation efficiency up to 76%. They also showed higher antioxidant activity than their base materials. Further, their anti-cancer efficacy was observed against MCF-7 breast cancer cells having IC50 values of 53.36±0.36μg/mL (chitosan-ascorbic acid-glucose), 55.28±0.85μg/mL (chitosan-Vitamin E), 63.72±0.27μg/mL (Chitosan-catechol) and 58.53±0.55μg/mL (chitosan-silver nanoparticles). Thus, the prepared formulations can be therapeutically applied for effective and targeted delivery in breast cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Sublingual immunotherapy in polysensitized patients: effect on quality of life.

    Science.gov (United States)

    Ciprandi, G; Cadario, G; Valle, C; Ridolo, E; Verini, M; Di Gioacchino, M; Minelli, M; Gangemi, S; Sillano, V; Colangelo, C; Pravettoni, V; Pellegrino, R; Borrelli, P; Fiorina, A; Carosso, A; Gasparini, A; Riario-Sforza, G G; Incorvaia, C; Puccinelli, P; Scurati, S; Frati, F

    2010-01-01

    Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients. To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis. We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer). The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P < .01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44. This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.

  20. The efficacy of a combined oral formulation of derquantel-abamectin against anthelmintic resistant gastro-intestinal nematodes of sheep in the UK.

    Science.gov (United States)

    Geurden, Thomas; Hodge, Andrew; Noé, Laura; Winstanley, Dana; Bartley, David J; Taylor, Mike; Morgan, Colin; Fraser, Sarah J; Maeder, Steven; Bartram, David

    2012-10-26

    The objective of the present studies was to evaluate the efficacy of a combined formulation (Startect(®) Dual Active Oral Solution for Sheep, Pfizer Animal Health) of derquantel (DQL) and abamectin (ABA) for the treatment of: (1) sheep experimentally infected with a moxidectin (MOX)-resistant isolate of Teladorsagia circumcincta, and (2) multi-drug resistant gastrointestinal nematode parasites under UK field conditions. In the first study, a total of 40 animals were allocated into 4 treatment groups, and were either left untreated or treated with DQL+ABA, MOX or ABA. Faecal samples were collected on days 1-5 and on day 7 after treatment to examine the reduction in faecal egg excretion and to evaluate the egg viability. On day 14 post treatment all animals were euthanised for abomasal worm counts. There was a 100% reduction in geometric mean worm counts for the DQL+ABA treated animals compared to the untreated control animals (P0.05) and ABA-treated (P=0.0004) animals was 12.4% and 71.8%, respectively. The data from the egg hatch assay (EHA) indicated that in the MOX-treated and the ABA-treated animals, the majority of the eggs hatched after treatment. In the field study, performed on four farms, animals were allocated into 6 groups of 11-15 animals each in order to conduct a faecal egg count reduction test (FECRT), based on arithmetic mean egg counts. One group of animals remained untreated, whereas the other animals were treated with DQL+ABA, MOX, fenbendazole (FBZ), levamisole (LV) or ivermectin (IVM). On each of the farms the reduction in egg excretion after treatment with FBZ, LV or IVM was below 95.0%, indicating anthelmintic resistance. The efficacy of DQL+ABA ranged from 99.1 to 100%, yielding significantly lower egg counts compared to the untreated control group (P ≤ 0.003). For MOX the egg counts were significantly (P ≤ 0.003) lower compared to the untreated group at each farm, with reductions varying from 98.2 to 100%. The post-treatment copro

  1. Sublingual immunotherapy not effective in house dust mite-allergic children in primary care

    NARCIS (Netherlands)

    de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roder, Esther; Hop, Wim C. J.; de Groot, Hans; de Jongste, Johan C.; van Wijk, Roy Gerth; Bindels, Patrick J. E.; van der Wouden, Johannes C.

    Background: Sublingual immunotherapy (SLIT) as a therapy for the treatment of allergic rhinitis in children might be acceptable as an alternative for subcutaneous immunotherapy. However, the efficacy of SLIT with house dust mite extract is not well established. Objective: To investigate whether SLIT

  2. Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care

    NARCIS (Netherlands)

    Roder, Esther; Berger, Marjolein Y.; Hop, Wim C. J.; Bernsen, Roos M. D.; de Groot, Hans; van Wijk, Roy Gerth

    Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in

  3. Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma

    DEFF Research Database (Denmark)

    Virchow, Johann Christian; Backer, Vibeke; Kuna, Piotr

    2016-01-01

    IMPORTANCE: The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma. OBJECTIVES: To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticos...

  4. Neutrophils negatively regulate induction of mucosal IgA responses after sublingual immunization.

    Science.gov (United States)

    Jee, J; Bonnegarde-Bernard, A; Duverger, A; Iwakura, Y; Cormet-Boyaka, E; Martin, T L; Steiner, H E; Bachman, R C; Boyaka, P N

    2015-07-01

    Induction of mucosal immunoglobulin-A (IgA) capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. Innate immune cells are known to play a central role in induction of IgA responses by mucosal vaccines, but the relative contribution of myeloid cell subsets to these responses has not firmly been established. Using an in vivo model of sublingual vaccination with Bacillus anthracis edema toxin (EdTx) as adjuvant, we examined the role of myeloid cell subsets for mucosal secretory IgA responses. Sublingual immunization of wild-type mice resulted in a transient increase of neutrophils in sublingual tissues and cervical lymph nodes. These mice later developed Ag-specific serum IgG responses, but not serum or mucosal IgA. Interestingly, EdTx failed to increase neutrophils in sublingual tissues and cervical lymph nodes of IKKβ(ΔMye) mice, and these mice developed IgA responses. Partial depletion of neutrophils before immunization of wild-type mice allowed the development of both mucosal and serum IgA responses. Finally, co-culture of B cells with neutrophils from either wild-type or IKKβ(ΔMye) mice suppressed secretion of IgA, but not IgM or IgG. These results identify a new role for neutrophils as negative regulators of IgA responses.

  5. Comparison of Drug Acceptance and Anxiety Between Intranasal and Sublingual Midazolam Sedation.

    Science.gov (United States)

    Shanmugaavel, A Karthikeyan; Asokan, Sharath; John, J Baby; Priya, P R Geetha; Raaja, M Thirumalai

    2016-01-01

    The purpose of the study was to assess and compare the changes in anxiety level and drug acceptance after intranasal and sublingual midazolam sedation. Forty three- to seven-year-olds were randomly assigned to Group A (N equals 20; 0.2 mg/kg intranasal midazolam sedation) or Group B (N equals 20; 0.2 mg/kg sublingual midazolam sedation) sedation. The anxiety levels at various time periods were assessed from recorded videos using the Venham clinical anxiety scale by two pediatric dentists. The acceptance of the drug administration was assessed using a four-point scale. The Wilcoxon signed rank test and Mann-Whitney U test were used for statistical analysis using SPSS 17.0 software. There was a significant decrease in anxiety level from baseline to 20 minutes after drug administration in Group A (Pintranasal route of drug administration. Both intranasal and sublingual administrations of midazolam were equally effective in reducing the child's anxiety. The sublingual route of drug administration was better accepted than the intranasal route.

  6. Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response

    NARCIS (Netherlands)

    Gisolf, J.; Westerhof, B.E.; Dijk, N. van; Wesseling, K.H.; Wieling, W.; Karemaker, J.M.

    2004-01-01

    Objectives We set out to determine the effect of sublingual nitroglycerin (NTG), as used during routine tilt testing in patients with unexplained syncope, on hemodynamic characteristics and baroreflex control of heart rate (HR) and systemic vascular resistance (SVR). Background Nitroglycerin is used

  7. Sublingual nitroglycerin administration in coronary computed tomography angiography: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Takx, Richard A.P. [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Sucha, Dominika; Leiner, Tim [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Park, Jakob [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); University of Heidelberg, Department of Cardiology, Heidelberg (Germany); Hoffmann, Udo [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States)

    2015-12-15

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Sublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes. (orig.)

  8. 78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

    Science.gov (United States)

    2013-06-06

    ... HUMAN SERVICES Food and Drug Administration Determination That SUBOXONE (Buprenorphine Hydrochloride and... (buprenorphine hydrochloride (HCl) and naloxone HCl) sublingual tablets, 2 milligrams (mg)/0.5 mg and 8 mg/2 mg... to approve abbreviated new drug applications (ANDAs) for buprenorphine HCl and naloxone HCl...

  9. Changes in sublingual microcirculatory flow index and vessel density on ascent to altitude

    NARCIS (Netherlands)

    Martin, Daniel S.; Goedhart, Peter; Vercueil, Andre; Ince, Can; Levett, Denny Z. H.; Grocott, Mike P. W.

    2010-01-01

    We hypothesized that ascent to altitude would result in reduced sublingual microcirculatory flow index (MFI) and increased vessel density. Twenty-four subjects were studied using sidestream dark-field imaging, as they ascended to 5300 m; one cohort remained at this altitude (n = 10), while another

  10. effect of pre-operative sub-lingual misoprostol versus intravenous ...

    African Journals Online (AJOL)

    2012-09-09

    Sep 9, 2012 ... infusion of oxytocin in reducing blood loss at Caesarean section operation. However, .... is the type 2 error, σ is the standard deviation, and d .... Table 3. Comparison of means of intravenous oxytocin versus sub-lingual misoprostol. Variable. Diff of mean. Std Error. Signif. 95%. CI. IV. Oxytoc. Sub-ling.

  11. Revised Dose Schema of Sublingual Buprenorphine in the Treatment of the Neonatal Opioid Abstinence Syndrome

    Science.gov (United States)

    Kraft, Walter K.; Dysart, Kevin; Greenspan, Jay S.; Gibson, Eric; Kaltenbach, Karol; Ehrlich, Michelle E.

    2010-01-01

    AIMS Over half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacologic therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS. DESIGN Randomized, phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine. SETTING Large, urban, tertiary care hospital. PARTICIPANTS Twenty-four term infants requiring pharmacological treatment for NAS. MEASUREMENTS Outcomes were neonatal safety, length of treatment, and length of hospitalization. FINDINGS Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (p=0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (p=0.05). CONCLUSIONS Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine. PMID:20925688

  12. Soluble insulin analogs combining rapid- and long-acting hypoglycemic properties – From an efficient E. coli expression system to a pharmaceutical formulation

    Science.gov (United States)

    Mikiewicz, Diana; Bierczyńska-Krzysik, Anna; Sobolewska, Agnieszka; Stadnik, Dorota; Bogiel, Monika; Pawłowska, Monika; Wójtowicz-Krawiec, Anna; Baran, Piotr A.; Łukasiewicz, Natalia; Romanik-Chruścielewska, Agnieszka; Sokołowska, Iwona; Stadnik, Jacek; Borowicz, Piotr; Płucienniczak, Grażyna; Płucienniczak, Andrzej

    2017-01-01

    The discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been introduced to insulin preparations. The availability of molecular genetic techniques has enabled the creation of insulin analogs by changing the structure of the native protein in order to improve the therapeutic properties. A new expression vector pIBAINS for production of four recombinant human insulin (INS) analogs (GKR, GEKR, AKR, SR) was constructed and overexpressed in the new E. coli 20 strain as a fusion protein with modified human superoxide dismutase (SOD). The SOD gene was used as a signal peptide to enhance the expression of insulin. SOD::INS was manufactured in the form of insoluble inclusion bodies. After cleavage of the fusion protein with trypsin, the released insulin analogs were refolded and purified by reverse-phase high performance liquid chromatography (RP-HPLC). Elongation of chain A, described here for the first time, considerably improved the stability of the selected analogs. Their identity was confirmed with mass spectrometric techniques. The biological activity of the insulin derivatives was tested on rats with experimental diabetes. The obtained results proved that the new analogs described in this paper have the potential to generate prolonged hypoglycemic activity and may allow for even less frequent subcutaneous administration than once-a-day. When applied, all the analogs demonstrate a rapid onset of action. Such a combination renders the proposed biosynthetic insulin unique among already known related formulations. PMID:28296883

  13. Soluble insulin analogs combining rapid- and long-acting hypoglycemic properties - From an efficient E. coli expression system to a pharmaceutical formulation.

    Science.gov (United States)

    Mikiewicz, Diana; Bierczyńska-Krzysik, Anna; Sobolewska, Agnieszka; Stadnik, Dorota; Bogiel, Monika; Pawłowska, Monika; Wójtowicz-Krawiec, Anna; Baran, Piotr A; Łukasiewicz, Natalia; Romanik-Chruścielewska, Agnieszka; Sokołowska, Iwona; Stadnik, Jacek; Borowicz, Piotr; Płucienniczak, Grażyna; Płucienniczak, Andrzej

    2017-01-01

    The discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been introduced to insulin preparations. The availability of molecular genetic techniques has enabled the creation of insulin analogs by changing the structure of the native protein in order to improve the therapeutic properties. A new expression vector pIBAINS for production of four recombinant human insulin (INS) analogs (GKR, GEKR, AKR, SR) was constructed and overexpressed in the new E. coli 20 strain as a fusion protein with modified human superoxide dismutase (SOD). The SOD gene was used as a signal peptide to enhance the expression of insulin. SOD::INS was manufactured in the form of insoluble inclusion bodies. After cleavage of the fusion protein with trypsin, the released insulin analogs were refolded and purified by reverse-phase high performance liquid chromatography (RP-HPLC). Elongation of chain A, described here for the first time, considerably improved the stability of the selected analogs. Their identity was confirmed with mass spectrometric techniques. The biological activity of the insulin derivatives was tested on rats with experimental diabetes. The obtained results proved that the new analogs described in this paper have the potential to generate prolonged hypoglycemic activity and may allow for even less frequent subcutaneous administration than once-a-day. When applied, all the analogs demonstrate a rapid onset of action. Such a combination renders the proposed biosynthetic insulin unique among already known related formulations.

  14. Premedication with benzodiazepines for upper gastrointestinal endoscopy: Comparison between oral midazolam and sublingual alprazolam

    Directory of Open Access Journals (Sweden)

    Vahid Sebghatollahi

    2017-01-01

    Full Text Available Background: Premedication with orally administered benzodiazepines is effective in reducing anxiety and discomfort related to endoscopic procedures. We evaluated the efficacy and safety of oral midazolam in comparison to sublingual alprazolam as premedication for esophagogastroduodenoscopy (EGD. Materials and Methods: Adult candidates for diagnostic EGD received either oral midazolam (7.5 mg in 15 cc apple juice or sublingual alprazolam (0.5 mg 30 min before EGD. Procedural anxiety and pain/discomfort were assessed using 11-point numerical rating scales. Patients' overall tolerance (using a four-point Likert scale and willingness to repeat the EGD, if necessary, were also assessed. Blood pressure, heart rate, and arterial oxygen saturation were monitored from medication to 30 min after the procedure. Results: Patients experienced a similar reduction in procedural anxiety after medication with oral midazolam and sublingual alprazolam; mean (standard deviation [SD] of 1.86 [1.63] and 2.02 [1.99] points, respectively, P = 0.91. Compared to oral midazolam, pain/discomfort scores were lower with sublingual alprazolam; mean (SD of 4.80 (3.01 versus 3.68 (3.28, P = 0.024. There was no significant difference between the two groups in patients' tolerance, willingness to repeat the procedure, or hemodynamic events. Conclusion: Oral midazolam and sublingual alprazolam are equally effective in reducing EGD-related anxiety; however, EGD-related pain/discomfort is lower with alprazolam. Both benzodiazepines are equally safe and can be used as premedication for patients undergoing diagnostic EGD.

  15. The clinical impact of vehicle technology using a patented formulation of benzoyl peroxide 5%/clindamycin 1% gel: comparative assessments of skin tolerability and evaluation of combination use with a topical retinoid.

    Science.gov (United States)

    Del Rosso, James Q; Tanghetti, Emil

    2006-02-01

    A major challenge encountered in clinical practice in patients with acne vulgaris is irritation related to topical medications used for treatment. Advances in vehicle technology have improved formulations containing active ingredients known to produce irritation in some patients, such as benzoyl peroxide (BP) and topical retinoids. Clinical studies, including combination therapy studies have demonstrated that certain additives, such as silicates and specific humectants, reduce irritation by maintaining barrier integrity. A patented gel formulation of BP 5%/clindamycin phosphate 1% (clindamycin) containing dimethicone and glycerin has been studied both as a monotherapy and in combination with topical retinoid use. This article evaluates specific vehicle additives included in this gel formulation and explains their role in reducing irritation. Data from clinical trials utilizing this technology in acne management are also reviewed.

  16. Pharmacokinetics of the evogliptin/metformin extended-release (5/1,000 mg fixed-dose combination formulation compared to the corresponding loose combination, and food effect in healthy subjects

    Directory of Open Access Journals (Sweden)

    Rhee SJ

    2016-04-01

    Full Text Available Su-jin Rhee,1,* SeungHwan Lee,1,2,* Seo Hyun Yoon,1 Joo-Youn Cho,1 In-Jin Jang,1 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: A new fixed-dose combination formulation of evogliptin 5 mg and metformin extended-release (XR 1,000 mg (FDC_EVO5/MET1000 was developed to improve medication adherence for type 2 diabetes mellitus. The pharmacokinetics of FDC_EVO5/MET1000 was compared to the corresponding loose combination in a randomized, open-label, crossover study in 36 healthy male subjects (Part 1, and the food effect on FDC_EVO5/MET1000 was assessed (under fasted or fed conditions in a randomized, open-label, crossover study in 28 healthy male subjects (Part 2. Serial blood samples for pharmacokinetic analysis were collected up to 72 hours, and pharmacokinetic parameters of evogliptin and metformin were calculated using non-compartmental methods. The geometric mean ratios (fixed-dose combination to loose combination and 90% confidence intervals of pharmacokinetic parameters for evogliptin and metformin were all within 0.800–1.250, suggesting bioequivalent pharmacokinetic. After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR. FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events. In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration. Keywords: pharmacokinetics, bioequivalence, food effect, fixed-dose combination, evogliptin, metformin XR

  17. Sublingual flagellin protects against acute pneumococcal pneumonia in a TLR5-dependent and NLRC4-independent fashion.

    Science.gov (United States)

    Muñoz-Wolf, Natalia; Rial, Analía; Fougeron, Delphine; Tabareau, Julien; Sirard, Jean-Claude; Chabalgoity, José A

    2016-09-01

    To evaluate efficacy of sublingual flagellin to treat acute pneumonia. Mice were treated sublingually with flagellin and challenged intranasally with a lethal dose of pneumococcus. Flagellins lacking TLR5 or NLRC4 activation domains were used to assess their contribution to protection. Sublingual flagellin protected mice in a TLR5-dependent, NLRC4-independent fashion. Neutrophils were required for protection. Flagellin-stimulated lung epithelial cells recapitulated the lung's transcriptional profile suggesting they could be targeted by flagellin in vivo. Ligation of TLR5, a pathogen recognition receptor not naturally engaged by pneumococcus, protects mice from invasive pneumonia when administered via sublingual route. This can be a highly cost-effective alternative therapy against pneumonia.

  18. Chemometrics-Assisted UV Spectrophotometric and RP-HPLC Methods for the Simultaneous Determination of Tolperisone Hydrochloride and Diclofenac Sodium in their Combined Pharmaceutical Formulation

    Science.gov (United States)

    Gohel, Nikunj Rameshbhai; Patel, Bhavin Kiritbhai; Parmar, Vijaykumar Kunvarji

    2013-01-01

    Chemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial least-square regression models. Two sets of standard mixtures, calibration sets, and validation sets were prepared. Both models were optimized to quantify each drug in the mixture using the information included in the UV absorption spectra of the appropriate solution in the range 241–290 nm with the intervals λ = 1 nm at 50 wavelengths. The optimized models were successfully applied to the simultaneous determination of these drugs in synthetic mixture and pharmaceutical formulation. In addition, an HPLC method was developed using a reversed-phase C18 column at ambient temperature with a mobile phase consisting of methanol:acetonitrile:water (60:30:10 v/v/v), pH-adjusted to 3.0, with UV detection at 275 nm. The methods were validated in terms of linearity, accuracy, precision, sensitivity, specificity, and robustness in the range of 3–30 μg/mL for TOL and 1–10 μg/mL for DIC. The robustness of the HPLC method was tested using an experimental design approach. The developed HPLC method, and the PCR and PLS models were used to determine the amount of TOL and DIC in tablets. The data obtained from the PCR and PLS models were not significantly different from those obtained from the HPLC method at 95% confidence limit. PMID:24482768

  19. Warfarin-induced sublingual hematoma mimicking Ludwig angina: Conservative management of a potentially life-threatening condition.

    LENUS (Irish Health Repository)

    Cashman, Emma

    2011-02-01

    Sublingual hematoma secondary to excessive anticoagulation is a rare, life-threatening condition. Reports in the literature have emphasized the importance of a prompt reversal of the causative coagulopathy by intravenous administration of vitamin K and fresh frozen plasma. In the event of an unstable airway, surgical intervention via tracheostomy or cricothyroidectomy is advocated. We report a case of sublingual hematoma that was treated conservatively, and we discuss the presentation and management of this entity.

  20. Warfarin-induced sublingual hematoma mimicking Ludwig angina: Conservative management of a potentially life-threatening condition.

    LENUS (Irish Health Repository)

    Cashman, Emma

    2012-02-01

    Sublingual hematoma secondary to excessive anticoagulation is a rare, life-threatening condition. Reports in the literature have emphasized the importance of a prompt reversal of the causative coagulopathy by intravenous administration of vitamin K and fresh frozen plasma. In the event of an unstable airway, surgical intervention via tracheostomy or cricothyroidectomy is advocated. We report a case of sublingual hematoma that was treated conservatively, and we discuss the presentation and management of this entity.

  1. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    Directory of Open Access Journals (Sweden)

    Moral A

    2016-06-01

    Full Text Available Angel Moral,1 Victoria Moreno,2 Francisco Girón,3 David El-Qutob,4 José D Moure,5 Manuel Alcántara,6 Antonia Padial,7 Alberto G Oehling,8 Carmen Millán,9 Fernando de la Torre10 1Allergy Service, Hospital Virgen del Valle, Toledo, 2Allergy Service, Hospital Blanca Paloma, Huelva, 3Consulta Privada, Granada, 4Allergy Service, Clínica Atenea, Castellón, 5Pediatric Department, Complejo Hospitalario Universitario de Santiago, A Coruña, 6Allergy Service, Complejo Hospitalario de Jaén, Jaén, 7Allergy Service, Hospital Infanta Sofía, Madrid, 8Centro de Alergia y Asma Balear, Mallorca, 9Consulta Privada, Cádiz, 10ALK-Abelló, SA, Madrid, Spain Background: Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy.Patients and methods: A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months.Results: The most frequent adverse reaction was oral pruritus (13.7% of the patients. Most of the reactions were local (84.7% and immediate (93.5% and occurred during the initiation phase (60.6%. All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417, age (P=0.1801, years since the disease was first

  2. Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.

    Science.gov (United States)

    Rascol, Olivier; Azulay, Jean-Philippe; Blin, Olivier; Bonnet, Anne-Marie; Brefel-Courbon, Christine; Césaro, Pierre; Damier, Philippe; Debilly, Bérengère; Durif, Frank; Galitzky, Monique; Grouin, Jean-Marie; Pennaforte, Sylvie; Villafane, Gabriel; Yaici, Sadek; Agid, Yves

    2010-02-15

    S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single-dose double-blind double-placebo 3 x 3 cross-over study. Optimal tested doses were determined during a previous open-label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (Delta UPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 +/- 8 years, PD duration: 12 +/- 6 years, UPDRS III OFF: 37 +/- 15) participated. S90049 was superior to placebo on Delta UPDRS III (-13 +/- 12 versus -7 +/- 9 respectively; estimated difference -5.2, 95% Confidence Interval (CI)[-10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, Delta UPDRS III was similar on S90049 (-21.2 +/- 10.1) and apomorphine (-23.6 +/- 14.1) (estimated difference: 4.0 95% CI [-2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. (c) 2009 Movement Disorder Society.

  3. Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa.

    Science.gov (United States)

    Vesikari, Timo; Rivera, Luis; Korhonen, Tiina; Ahonen, Anitta; Cheuvart, Brigitte; Hezareh, Marjan; Janssens, Winnie; Mesaros, Narcisa

    2017-07-03

    Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12-15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1-3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued.

  4. Reduced sublingual endothelial glycocalyx in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Winther, Signe Abitz; Frimodt-Møller, Marie; Zobel, Emilie Hein

    - and macroalbuminuric patients (p=0.020) and micro- and macroalbuminuric patients (p=0.042) were significant, but the difference between normo- and microalbuminuric patients was not (p=0.74). After adjustment for age, sex, HbA1c, diabetes duration and systolic blood pressure, differences between normo...... of easy and non-invasive quantification tools. With capillaroscopy it is possible to visualize the sublingual capillaries by sidestream dark field imaging and estimates the dimensions of the glycocalyx by measuring the perfused boundary region (PBR). We evaluated the glycocalyx thickness non-invasively...... thickness was assessed by 5 measurements with the GlucoCheck device (GlucoCheck BV, The Netherlands), a non-invasive hand-held microscope generating video recordings of the sublingual capillaries. Endothelial glycocalyx thickness was estimated from the PBR in capillaries with a diameter range of 5-25 μm...

  5. CHANGES OF IMMUNE INDEXES DURING SUBLINGUAL ALLERGEN-SPECIFIC IMMUNOTHERAPY IN CHILDREN WITH HAY FEVER

    Directory of Open Access Journals (Sweden)

    I. M. Gaiduk

    2013-01-01

    Full Text Available Aims of study: evaluation of immunological parameters in course of sublingual allergen-specific immunotherapy with tree pollen mixture in children with hay fever.Materials and methods: the study included one-hundred patients 5 to 18 years of age with hay fever (pollen rhinitis, rhinoconjunctivitis and/or asthma. Allergen-specific immunotherapy was administered pre-seasonally for three consecutive years. Cytokinechanges were studied in blood serum and in lavages from nasal cavity. Samples assessed before treatment and after 2nd and 3rd courses SLIT completion.Results: increased serum concentrations of IL-10, IFNγ, and decreased IL-4 contents were revealed in the course of treatment. No significant changes in cytokineconcentrations were detectable in nasal lavages.Conclusions: the changes revealed correspond to a shift of T cell response profile towards Th1 pathway, thus confirming pathogenetic effects of sublingual allergen-specific

  6. Distinct modulation of allergic T cell responses by subcutaneous versus sublingual allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Schulten, Véronique; Tripple, Victoria; Andersen, Kristian Aasbjerg

    2016-01-01

    BACKGROUND: Allergen-specific immunotherapy is the only curative treatment for type I allergy. It can be administered subcutaneously (SCIT) or sublingually (SLIT). The clinical efficacy of these two treatment modalities appears to be similar, but potential differences in the immunological...... mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen allergic patients were randomized into groups receiving either SCIT...... was observed starting 10 months after treatment was commenced. At 24 months, T cell responses showed IL-5 levels significantly below the before treatment baseline. No significant reduction of IL-5 was observed in the SLIT or untreated group. However, a significant transient increase in IL-10 production after...

  7. Rigid swelling of sublingual caruncle area due to the salivary gland duct obstruction by a sialolith*

    Science.gov (United States)

    Bernardes Filho, Fred; Martins, Gustavo; Alves, Andreia Oliveira; da Costa, José Ronaldo Vieira; Azulay, David Rubem; Azulay-Abulafia, Luna

    2014-01-01

    Sialolithiasis is the presence of calculus within the ductal system of a salivary gland. Among the diagnostic methods are inspection, palpation, checking the amount of saliva secreted and the identification of a sialolith. The authors present the case of a 37-year-old female patient with edema of the submandibular area and a bulging sublingual caruncle due to a calculus that obstructed the salivary gland ostium. PMID:25387506

  8. Sublingual sugar for hypoglycaemia in children with severe malaria: A pilot clinical study

    Directory of Open Access Journals (Sweden)

    Giani Sergio

    2008-11-01

    Full Text Available Abstract Background Hypoglycaemia is a poor prognostic indicator in severe malaria. Intravenous infusions are rarely feasible in rural areas. The efficacy of sublingual sugar (SLS was assessed in a pilot randomized controlled trial among hypoglycaemic children with severe malaria in Mali. Methods Of 151 patients with presumed severe malaria, 23 children with blood glucose concentrations = 3.3 mmol/l (60 mg/dl within 40 minutes after admission. Secondary outcome measures were early treatment response at 20 minutes, relapse (early and late, maximal BGC gain (CGmax, and treatment delay. Results There was no significant difference between the groups in the primary outcome measure. Treatment response occurred in 71% and 67% for SLS and IVG, respectively. Among the responders, relapses occurred in 30% on SLS at 40 minutes and in 17% on IVG at 20 minutes. There was one fatality in each group. Treatment failures in the SLS group were related to children with clenched teeth or swallowing the sugar, whereas in the IVG group, they were due to unavoidable delays in beginning an infusion (median time 17.5 min (range 3–40. Among SLS, the BGC increase was rapid among the nine patients who really kept the sugar sublingually. All but one increased their BGC by 10 minutes with a mean gain of 44 mg/dl (95%CI: 20.5–63.4. Conclusion Sublingual sugar appears to be a child-friendly, well-tolerated and effective promising method of raising blood glucose in severely ill children. More frequent repeated doses are needed to prevent relapse. Children should be monitored for early swallowing which leads to delayed absorption, and in this case another dose of sugar should be given. Sublingual sugar could be proposed as an immediate "first aid" measure while awaiting intravenous glucose. In many cases it may avert the need for intravenous glucose.

  9. Variability in sublingual microvessel density and flow measurements in healthy volunteers.

    Science.gov (United States)

    Hubble, Sheena M A; Kyte, Hayley L; Gooding, Kim; Shore, Angela C

    2009-02-01

    As sublingual microvascular indices are increasingly heralded as new resuscitation end-points, better population data are required to power clinical studies. This paper describes improved methods to quantify sublingual microvessel flow and density in images obtained by sidestream dark field (SDF) technology in healthy volunteers, including vessels under 10 microm in diameter. Measurements of sublingual capillary density and flow were obtained by recording three 15-second images in 20 healthy volunteers over three days. Two independent observers quantified capillary density by using two methods: total vessel length (mm/mm2) and counting (number/mm). Both intraoral and temporal variabilities within subject and observer reproducibilities were determined by using coefficients of variability and reproducibility indices. For small (1-10 microm), medium (11-20 microm), and large (21-50 microm) diameter, mean vessel density with standard deviations (SDs) in volunteers was 21.3(+/- 4.9), 5.2 (+/- 1.2), and 2.7 (+/- 0.9) mm/mm2, respectively. Also, 94.0 +/- 1.4% of small vessels, 94.5 +/- 1.4% of medium vessels, and 94.5+/- 4.0% of large vessels had continuous perfusion. Within subjects, the means of all measurements over three days varied less than 13, 22, and 35% in small, medium, and large vessels, respectively. Interobserver reproducibility was good, especially for capillary (1-10 microm) density and flow measurements. Our methods of microvessel flow and density quantification have low observer variability and confirm the stability of microcirculatory measurements over time. These results facilitate the development of SDF-acquired sublingual microvascular indices as feasible microperfusion markers in shock resuscitation.

  10. The Proteomes of Human Parotid and Submandibular/Sublingual Gland Salivas Collected as the Ductal Secretions

    OpenAIRE

    Denny, Paul; Hagen, Fred K.; Hardt, Markus; Liao, Lujian; Yan, Weihong; Arellanno, Martha; Bassilian, Sara; Bedi, Gurrinder S.; Boontheung, Pinmannee; Cociorva, Daniel; Delahunty, Claire M.; Denny, Trish; Dunsmore, Jason; Faull, Kym F.; Gilligan, Joyce

    2008-01-01

    Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications—914 in parotid and 917 in submandibular/sublingual saliva—were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes...

  11. The impact of the site of blood sampling on pharmacokinetic parameters following sublingual dosing to dogs.

    Science.gov (United States)

    Sohlberg, E; Halldin, M M; Annas, A; Königsson, K; Jansson, B; Pehrson, R; Borg, N

    2013-01-01

    Drugs are most commonly administered orally, but some potential drug candidates are not suited for oral administration due to poor absorption, high first pass metabolism or gastrointestinal side effects. The interest for transmucosal dosing for systemic drug delivery is increasing, e.g. buccal, sublingual and nasal routes. The evaluation of the systemic plasma concentration and the derivation of the pharmacokinetic parameters of candidate compounds in preclinical studies are essential for drug development. The effect of site of blood sampling on the measured drug concentration, in both animals and humans, is to some extent known but it is not always taken into consideration in the design of pharmacological and toxicological studies. Blood samples were collected both from leg and jugular veins from beagle dogs following a single sublingual dosing of Compound A in order to determine the impact of different sites of blood sampling on plasma pharmacokinetics. Plasma was prepared by centrifugation and plasma concentrations of Compound A were determined by protein precipitation and liquid chromatography followed by mass spectrometric detection. The pharmacokinetic parameters were calculated by non-compartment methods. Sampling from the jugular vein resulted in higher and more variable exposure during the absorption phase compared to sampling from a leg vein. The plasma exposure in the jugular vein, in terms of C(max), was 4-fold compared to that in the leg vein and an approximately 2-fold bioavailability was observed. The aim of this investigation was to determine the impact of the different sites of blood sampling on assessing systemic plasma exposure and pharmacokinetic parameters for Compound A following sublingual dosing to dogs. The results demonstrate the significant impact that the site of blood sampling has on PK parameters, and raise concerns of using the jugular vein as a site of sampling after sublingual and other transmucosal routes of dosing in the head

  12. Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients.

    Science.gov (United States)

    Ruiz, Carolina; Hernandez, Glenn; Godoy, Cristian; Downey, Patricio; Andresen, Max; Bruhn, Alejandro

    2010-01-01

    Previous studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients. This was a prospective, non-randomized study at a 16-bed, medical-surgical intensive care unit of a university hospital. We included 12 severe hyperdynamic septic shock patients (norepinephrine requirements > 0.3 μg/kg/min and cardiac index > 3.0 L/min/m2) who underwent a 12-hour HVHF as a rescue therapy according to a predefined algorithm. Sublingual microcirculation (Microscan for NTSC, Microvision Medical), systemic hemodynamics and perfusion parameters were assessed at baseline, at 12 hours of HVHF, and 6 hours after stopping HVHF. Microcirculatory flow index increased after 12 hours of HVHF and this increase persisted 6 hours after stopping HVHF. A similar trend was observed for the proportion of perfused microvessels. The increase in microcirculatory blood flow was inversely correlated with baseline levels. There was no significant change in microvascular density or heterogeneity during or after HVHF. Mean arterial pressure and systemic vascular resistance increased while lactate levels decreased after the 12-hour HVHF. The use of HVHF as a rescue therapy in patients with severe hyperdynamic septic shock does not deteriorate sublingual microcirculatory blood flow despite the increase in systemic vascular resistance.

  13. [Efficacy of the dust mites drops sublingual immunotherapy in pediatric allergic rhinitis].

    Science.gov (United States)

    Xie, Lisheng; Jiang, Yinzhu; Li, Qi

    2016-03-01

    To observe the role of the dust mites drops sublingual immunotherapy(SLIT) in pediatric allergic rhiriitis caused by dust mites and compare its efficacy between monosensitized and polysensitized children. A total of 77 pediatric allergic rhinitis patients received Dermatophagoides farina extracts sublingual immunotherapy for 2 years were enrolled as desensitization group and were allocated into monosensitized group (41 cases) and polysensitized group (36 cases) according to the number of coexisting allergens. Meanwhile another 33 allergic rhinitis children treated by pharmacotherapy during the period were collected as control group. The total symptom scores (TNSS), total medication scores (TMS) and visual analogue scale(VAS) were assessed at the beginning, six months, 1 year and 2 years of the treatment. SPSS 13. 0 software was used to analyze the data. the score of TNSS and VAS in desensitization was slightly higher than the control after six months treatment, but without difference at l year and 2 years; the score of TMS had significantly improved in desensitization compared with the corresponding points in control. All the parameters in monosensitized group were equivalent with polysensitizend group, except the score of TMS was slightly lower than the polysensitizend group at six months. Dust mite drops sublingual immunotherapy is effective for the allergic rhinitis children caused by mites. And it has similar immunotherapy efficacy between monosensitized and polysensitized children.

  14. Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a decrease in sublingual perfusion.

    Science.gov (United States)

    Smit, B; Smulders, Y M; Eringa, E C; Gelissen, H P M M; Girbes, A R J; de Grooth, H J S; Schotman, H H M; Scheffer, P G; Oudemans-van Straaten, H M; Spoelstra-de Man, A M E

    2017-12-06

    To determine the human dose-response relationship between a stepwise increase in arterial oxygen tension and its associated changes in oxygen delivery and sublingual microcirculatory perfusion METHODS: Fifteen healthy volunteers breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen tensions of baseline (breathing air), 20 kPa, 40 kPa, 60 kPa and max kPa (breathing oxygen). Systemic hemodynamics were measured continuously by the volume-clamp method. At the end of each period, the sublingual microcirculation was assessed by Sidestream Darkfield Imaging RESULTS: Systemic oxygen delivery was unchanged throughout the study (Pslope =0.8). Perfused vessel density decreased in a sigmoidal fashion (max -15% while breathing oxygen, SD18, Pslope =0.001). Cardiac index decreased linearly (max -10%, SD10, Pslope <0.001) due to a reduction in heart rate (max -10%, SD7, Pslope =0.009). There were no changes in stroke volume or mean arterial pressure. Most changes became apparent above an arterial oxygen tension of 20 kPa CONCLUSIONS: In healthy volunteers, supraphysiological arterial oxygen tensions have no effect on systemic oxygen delivery. Sublingual microcirculatory perfused vessel density decreased in a dose-dependent fashion. All hemodynamic changes appear negligible up to an arterial oxygen tension of 20 kPa This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Sublingual Nucleotides Prolong Run Time to Exhaustion in Young Physically Active Men

    Directory of Open Access Journals (Sweden)

    Sergej M. Ostojic

    2013-11-01

    Full Text Available Although dietary nucleotides have been determined to be required for normal immune function, there is limited direct interventional evidence confirming performance-enhancing effects of sublingual nucleotides in humans. A double-blind, placebo-controlled, randomized trial was conducted to evaluate the effect of sublingual nucleotides (50 mg/day administered for 14 days in thirty young healthy physically active males, on endurance performance and immune responses. Fasting white blood cell count, natural killer cells (NKC number, NKC cytotoxic activity, and serum immunoglobulin (IgA, IgM, IgG, and time to exhaustion, peak rate of perceived exertion, peak heart rate, and peak running speed during the exercise test were measured at baseline (day 0 and post-intervention (day 14. Time to exhaustion, as well as serum immunoglobulin A and NKC cytotoxic activity, were significantly higher at day 14 (p < 0.05 in participants supplemented with nucleotides compared with those who consumed placebo. No significant differences in other parameters were observed between groups at post-intervention. No volunteers withdrew before the end of the study nor reported any vexatious side effects of supplementation. The results of the present study suggest that sublingual nucleotides may provide pertinent benefit as both an ergogenic and immunostimulatory additive in active males.

  16. Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial.

    Science.gov (United States)

    Lima, M Torres; Wilson, D; Pitkin, L; Roberts, A; Nouri-Aria, K; Jacobson, M; Walker, S; Durham, S

    2002-04-01

    Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose-ranging studies.

  17. Quality by Design (QbD) approach to optimize the formulation of a bilayer combination tablet (Telmiduo(®)) manufactured via high shear wet granulation.

    Science.gov (United States)

    Lee, Ah Ram; Kwon, Seok Young; Choi, Du Hyung; Park, Eun Seok

    2017-10-12

    A bilayer tablet, which consisted of telmisartan and amlodipine besylate, was formulated based on a Quality by Design (QbD) approach. The control and response factors were determined based on primary knowledge and the target values of the control tablet (Twynsta(®)). A D-optimal mixture design was used to obtain the optimal formulations in terms of D-mannitol, crospovidone, and MCC for the telmisartan layer, and CCM-Na, PVP K25, and Prosolv for the amlodipine layer. The quantitative effects of the different formulation factors on the response factors were accurately predicted using the equations of best fit and a strong linearity was observed between the predicted and actual values of the response factors. The optimized bilayer tablet was obtained using a numeric optimization technique and was characterized compared with a control (Twynsta(®)) by using various physical evaluations and in vivo pharmacokinetic parameters. The physical stability of Telmiduo(®) was greater than that of Twynsta(®) owing to the improvement of formulation factors. The in vivo pharmacokinetic parameters suggested that Telmiduo(®) might have pharmaceutical equivalence and bioequivalence with Twynsta(®). Therefore, the bilayer tablet that consisted of telmisartan and amlodipine besylate could be produced using a more economical and simpler method than that used to produce Twynsta(®). Moreover, the suitability of QbD for effective product development in the pharmaceutical industry was shown. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Efficacy and safety of a nano-emulsion gel formulation of adapalene 0.1% and clindamycin 1% combination in acne vulgaris: A randomized, open label, active-controlled, multicentric, phase IV clinical trial

    Directory of Open Access Journals (Sweden)

    Siva Prasad

    2012-01-01

    Full Text Available Background: Acne vulgaris is a very common skin disease with a significant detrimental effect on the quality of life of the patients. Aims: To assess the comparative efficacy and safety of a nano-emulsion gel formulation of adapalene and clindamycin combination with its conventional formulation in the treatment of acne vulgaris of the face. It was a prospective, randomized, open label, active-controlled, multicentric, clinical trial. Methods: Eligible patients suffering from acne vulgaris of the face were randomized to receive once-daily treatment with a nano-emulsion gel or conventional gel formulation of adapalene 0.1% and clindamycin (as phosphate 1% combination for 12 weeks. Total, inflammatory and noninflammatory lesion counts, with grading of acne severity were carried out on a monthly basis. Safety assessments were done to determine the comparative local and systemic tolerability. Two-tailed significance testing was carried out with appropriate statistical tests, and P-values < 0.05 were considered as significant. Results: 209/212 patients enrolled in the study were eligible for efficacy and safety assessments in both nano-emulsion gel (118/119 patients and conventional gel (91/93 patients groups. Significantly better reductions in total (79.7% vs. 62.7%, inflammatory (88.7% vs. 71.4% and noninflammatory (74.9% vs. 58.4% lesions were reported with the nano-emulsion gel as compared to the conventional gel (P < 0.001 for all. Mean acne severity score also reduced significantly more with the nano-emulsion formulation (1.9 ± 0.9 vs. 1.4 ± 1.0; P < 0.001 than the comparator. Significantly lower incidence and lesser intensity of adverse events like local irritation (4.2% vs. 19.8%; P < 0.05 and erythema (0.8% vs. 9.9%; P < 0.05 were recorded with the nano-emulsion gel. Conclusions: The nano-emulsion gel formulation of adapalene and clindamycin combination appears to be more efficacious and better tolerated than the conventional formulation

  19. [Efficacy of individualized sublingual immunotherapy with dermatophagoides farinae drops on patients with allergic rhinitis of different age groups].

    Science.gov (United States)

    Liu, Jiping; Hu, Xiaoxun; Fu, Shucai; Wu, Chunxuan; Chen, Heling; Zhang, Min

    2014-03-01

    To evaluate the efficacy of personal sublingual immunotherapy (SLIT) with dermatophagoides to study the efficacy of dermatophagoides farinae drops for allergic rhinitis (AR) of different age groups. The current study had analyzed the efficacy of SLIT in 150 patients with AR who were sensitized to house dust mites. All patients were treated with dermatophagoides farinae drops and combined with symptomatic treatment. The patients were divided into groups 1-5, group 1:17 patients (4-7 years old), group 2: 38 patients (> 7-12 years old), group 3:31 patients (> 12-18 years old), group 4: 38 patients (> 18 - 40 years old), group 5: 26 patients (> 40-63 years old). The total nasal symptom scores (TNSS) and total medicine scores (TMS) were recorded at each visit. Before and after SLIT for 0.5 year, 1 year and 1.5 to 2.0 years, the TNSS and TMS of each patient were evaluated. The dosage adjustment of immunotherapy according to the patient's symptoms were performed. The TNSS and TMS had continuously improved significantly after SLIT for half year, 1 year and 1.5 to 2.0 years in all groups as compared with baseline (P differences in the different age groups for TNSS and TMS during all time points. Individualized SLIT with dermatophagoides farinae drops for 1.5-2.0 years is the most effective in the patients with allergic rhinitis of different age groups. And equivalent efficacy could be achieved for different age groups.

  20. SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms

    DEFF Research Database (Denmark)

    Mosbech, Holger; Canonica, G Walter; Backer, Vibeke

    2015-01-01

    BACKGROUND: House dust mite (HDM) allergy is associated with persistent allergic rhinitis (AR) and allergic asthma. OBJECTIVE: To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory...... allergic disease and report the AR results. METHODS: Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were randomized 1:1:1:1 to double-blinded daily treatment with 1, 3, 6 SQ-HDM or placebo. End-of-treatment rhinoconjunctivitis symptoms and medication...... score were predefined extrapulmonary end points. A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score (TCRS) > 0 (ie, with AR symptoms and/or AR medication use during the 4-week baseline period). The subgroup was comprised of 498 subjects (82%). RESULTS...

  1. [Matrix formulation of chaizhi cataplasma optimized by D-optimal mixture design combined with multiple mechanical indicators and its in vitro evaluation].

    Science.gov (United States)

    Zhang, Ye-Wen; Yu, Jing-Xin; Wang, Jing-Yan; Ru, Qing-Guo; Liu, Yan; Wang, Yi-Fei; Lin, Hong-Mei; Wu, Qing

    2016-03-01

    To optimize the matrix formulation of Chaizhi cataplasma (CC) and investigate its release and transdermal absorption properties in vitro. The optimized matrix formulation of cataplasma containing liquid herbal extract is determined by using D-optimal mixture design, with initial bonding strength, endurance bonding strength and gel strength as the evaluating indicators. Modified Franz diffusion cells were used to study the in vitro release and transdermal absorption of geniposide in CC. The optimized matrix formulation of CC contained NP700, aluminum glycinate, tartaric acid, glycerin, PVPK90 and water (9∶0.7∶0.8∶30∶5∶30.5). Cumulative release rate of geniposide in CC was (77.02±3.73)% in 24 h. The percutaneous penetration rate of geniposide was 7.25 μg•cm⁻²•h⁻¹ and the 24 h permeated amount was (156.22±4.90) μg•cm⁻². The optimized CC prepared by the D-optimal mixture design showed a good adhesion and formability. The in vitro release of the geniposide in CC was in accordance with the first order equation, while its in vitro transdermal absorption was close to the zero order equation. Copyright© by the Chinese Pharmaceutical Association.

  2. Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: Study design and recruitment

    NARCIS (Netherlands)

    C.M.A. de Bot (Cindy); H. Moed (Heleen); M.Y. Berger (Marjolein); E. Röder (Esther); H. de Groot (Hans); J.C. de Jongste (Johan); R. Gerth van Wijk (Roy); J.C. van der Wouden (Hans)

    2008-01-01

    textabstractBackground. For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A

  3. Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care : study design and recruitment

    NARCIS (Netherlands)

    de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roder, Esther; de Groot, Hans; de Jongste, Johan C.; van Wijk, Roy Gerth; van der Wouden, Johannes C.

    2008-01-01

    Background: For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized

  4. Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Didier, Alain; Worm, Margitta; Horak, Friedrich

    2011-01-01

    Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies.......Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies....

  5. Formulation development and evaluation of fast disintegrating tablets of salbutamol sulphate, cetirizine hydrochloride in combined pharmaceutical dosage form: a new era in novel drug delivery for pediatrics and geriatrics.

    Science.gov (United States)

    Sharma, Deepak; Singh, Gurmeet; Kumar, Dinesh; Singh, Mankaran

    2015-01-01

    The objective of the present study was to prepare the fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form for respiratory disorders such as bronchitis, asthma, and coughing for pediatrics and geriatrics. The tablets were prepared by direct compression technique. Superdisintegrant such as Sodium Starch Glycolate was optimized as 4% on the basis of least disintegration time. Different binders such as MCC and PVP K-30 were optimized along with optimized superdisintegrant concentration. 1% MCC was selected as optimum binder concentration on the basis of least disintegration time. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and drug content uniformity. Optimized formulation was further evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. Percent weight variation and content uniformity were within the acceptable limit. The friability was less than 1%. The wetting time and disintegration time were practically good for all formulations. FTIR studies and accelerated stability study showed that there was no interaction between the drug and excipients. It was concluded that, by employing commonly available pharmaceutical excipients such as superdisintegrants, hydrophilic and swellable excipients and proper filler, a fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form, were formulated successfully with desired characteristics.

  6. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen

    Directory of Open Access Journals (Sweden)

    Hanna L. Thim

    2014-03-01

    Full Text Available Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV as the test Ag, the combined use of two Toll-like receptor (TLR ligand adjuvants, CpG oligonucleotides (ODNs and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV glycoprotein (G was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing

  7. The efficacy of sublingual immunotherapy for respiratory allergy is not affected by different dosage regimens in the induction phase.

    Science.gov (United States)

    Sambugaro, R; Puccinelli, P; Burastero, S E; Di Rienzo, V

    2003-01-01

    Sublingual administration of allergens is a safe and effective alternative to subcutaneous immunotherapy in patients with respiratory allergies. A drawback to this therapeutic approach is the relatively long and complex management of the induction phase. To determine whether different induction regimens affect the outcome of sublingual immunotherapy. Adult and pediatric patients with allergic rhinoconjunctivitis and/or asthma were included in the study. Ten subjects served as controls and received symptomatic treatments. Forty-three subjects were allocated to sublingual immunotherapy, with three different induction protocols (8-, 15- and 20-day, respectively). Symptom and medication scores, skin test results and (in asthmatic patients) FEV1 values were monitored for two years. Adverse effects were recorded. All induction regimens produced a significant improvement in symptom and medication usage (p protocol is safe and effective. Our results encourage the usage of shorter induction regimens, which produce better compliance with this therapy.

  8. Airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy

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    Hua Xiang

    2016-07-01

    Full Text Available Objective: To evaluate the airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy. Methods: A total of 68 children with dust mite allergic rhinitis treated in our hospital from November, 2012 to October, 2015 were selected as the research subjects and randomly divided into observation group 34 cases and control group 34 cases. The control group received clinical routine therapy for allergic rhinitis, the observation group received sublingual immunotherapy, and then differences in basic lung function indicator values, small airway function indicator values and levels of serum inflammatory factors as well as serum ECP, TARC, Eotaxin-2 and VCAM were compared between two groups after treatment. Results: The FVC, FEV1, PEF and FEV1/FVC values of the observation group after treatment were higher than those of the control group (P<0.05; the MMEF, MEF50% and MEF25% values of the observation group were higher than those of the control group, and the proportion of AHR was lower than that of the control group (P<0.05; the serum IL-4, IL-9, IL-12, IL-13 and IL-16 levels of the observation group after treatment were lower than those of the control group, and the IL-10 and IL-12 levels are higher than those of the control group (P<0.05; the serum ECP, TARC, Eotaxin-2 and VCAM levels of the observation group children after treatment were lower than those of the control group (P<0.05. Conclusions: Sublingual immunotherapy for children with dust mite allergic rhinitis can optimize the airway function, reduce the systemic inflammatory response and eventually improve the children’s overall state, and it’s has positive clinical significance.

  9. ROLE OF 400 MCG INTRAOPERATIVE SUBLINGUAL MISOPROSTOL FOR REDUCTION OF CAESAREAN BLOOD LOSS

    Directory of Open Access Journals (Sweden)

    Lalmohan Nayak

    2017-02-01

    Full Text Available BACKGROUND Lower segment caesarean section is a common surgical procedure. Postpartum haemorrhage incidence after LSCS is 4%. Misoprostol is a prostaglandin E1 analogue with good uterotonic properties, easy availability, low cost, thermostability, long shelf life, easy administration and few adverse effects at therapeutic dose. It is readily absorbed by oral, sublingual, buccal, vaginal or rectal route. Sublingual route attains quickest concentration. Dose of 400 mcg was chosen in this study to minimise adverse effects with optimal therapeutic benefit. The aim of the study is to determine the efficacy of sublingual misoprostol in reducing caesarean blood loss. MATERIALS AND METHODS It is a prospective experimental study done in VSSIMSAR, Burla. Women undergoing LSCS were randomly assigned to study and control groups of equal strength of 100 each. In all cases, preoperative Hb%, haematocrit, pulse, BP was noted. Study group were given 400 mcg misoprostol at the time of cord clamping. In control group, nothing was given. In all patients, active management of third stage of labour was done by using oxytocin 10 IU (IV along with uterine massage. Blood loss soaked by tetra was calculated using formula, blood loss = wet weight-dry weight/1.05 (1.05 is constant. Amount of blood loss, postoperative Hb%, haematocrit, pulse rate, BP was noted in both groups and compared. BP and pulse were noted after 1 hour and Hb%, haematocrit were noted after 24 hours. RESULTS Study group showed significant decrease in total blood loss (around 117.9 mL as compared to control group. There was significant decrease in the postoperative fall in Hb in the study group as compared to control, the mean difference being 0.631 gm%. Study group also showed decrease in postoperative fall in haematocrit as compared to control, the mean difference being 0.055. CONCLUSION Misoprostol significantly reduced caesarean blood loss and doesn’t affect foetal outcome without significant

  10. Ultrastructural changes in the sublingual salivary gland of prenatal buffalo (Bubalus bubalis

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    A. D. Singh

    2016-03-01

    Full Text Available Aim: The present study was aimed to elucidate ultrastructural changes in the development of sublingual salivary gland of buffalo during prenatal life. Materials and Methods: The study was carried out on sublingual salivary gland of 36 buffalo fetuses ranging from 13.2 cm curved crown-rump length (CVRL (88th day to full term. The fetuses were categorized into three groups based on their CVRL. Results: The cells lining the terminal tubules were undifferentiated with poorly developed cytoplasmic organelles but lacked secretory granules (SGs at 13.2 cm CVRL (88th day. The SGs appeared first in the form of membrane-bound secretory vesicles with homogeneous electron-dense as well as electron-lucent contents at 21.2 cm CVRL (122nd day; however, mucous acinar cells contained electron-lucent granules, while serous secretory cells as well as serous demilunes showed electron-dense granules at 34 cm CVRL (150th day of prenatal life. At 53.5 cm CVRL (194th day, both mucous and serous acini were differentiated by the density of SGs. Conclusion: The cytoplasm of acinar cells was filled with mitochondria, rough endoplasmic reticulum, and Golgi profiles in mid and late fetal age groups. The SGs were increased in number during the late fetal age group. The myoepithelial cells (MECs were located at the base of the acinar cells as well as intercalated and striated ducts and were stellate in shape. The ultrastructure of MEC revealed a parallel stream of myofilaments in the cytoplasm and its processes. The mucous cells were predominantly present in the sublingual salivary gland and were pyramidal in shape.

  11. Adverse reaction to sublingual Parietaria vaccine following an ultra-rush induction.

    Science.gov (United States)

    Scala, G; Ciccarelli, A; Calabrò, C

    2014-05-01

    In the treatment of respiratory allergies Sublingual Immunotherapy (SLIT) represents a valid alternative to Subcutaneous Immunotherapy (SCIT) for its better safety profile. We describe a case of acute severe asthma following the first maintenance dose of SLIT in a boy allergic to Parietaria pollen. At the initiation of therapy, the patient was in healthy condition and his asthma appeared to be under control. An ultra-rush induction had given no reaction. Despite the good safety profile of SLIT, clinicians should be aware of the risk of adverse effects when prescribing SLIT for respiratory allergies.

  12. Sublingual misoprostol versus intravenous oxytocin in the management of postpartum hemorrhage

    Directory of Open Access Journals (Sweden)

    Beigi A

    2009-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Postpartum hemorrhage is a major cause of maternal mortality and morbidity. It has been identified that active management of third stage of labor is an effective way in preventing postpartum hemorrhage. This randomized controlled trial was conducted to compare sublingual misoprostol versus intravenous oxytocin in the management of postpartum hemorrhage in nulliparous women."n"nMethods: In this randomized controlled trial conducted in Arash hospital from 2006 to 2009, Five hundred forty two nulliparous pregnant women were enrolled. They were randomized to receive either 400 microgram sublingual misoprostol or 20 IU oxytocin intravenously, immediately after the birth of newborn. "n"nResults: Post partum Hemorrhage was significantly lower in women who received sublingual misoprostol (p<0.0001. Patients who received misoprostol had shorter length of third stage of labor (6.45 minute in misoprostol Vs 6.9 minute in oxytocin group, p=0.003. Comparison of hemoglobin levels in two groups before and after delivery showed that there is a significant lesser hemoglobin drop in misoprostol group p=0.046. Side effects were more common in misoprostol group (p<0.0001. However, they were not serious; shivering (35.66% in

  13. A Rare Primary Neuroendocrine Tumor (Typical Carcinoid of the Sublingual Gland

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    Kenji Yamagata

    2016-01-01

    Full Text Available A typical carcinoid is extremely rare in the oral cavity. We here present a case of a typical carcinoid arising in the sublingual gland of a 62-year-old woman. The tumor was removed by primary excision with 10 mm surgical margins and submandibular dissection. Examination of the tumor showed medium-sized tumor cells that were positive for CD56 and chromogranin A, with no necrosis, and with a mitotic count less than 1/10 HPF. A pathological diagnosis of typical carcinoid was made from both morphological and immunological examinations. One year after excision surgery, there was no tumor recurrence or neck metastasis.

  14. Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy.

    Science.gov (United States)

    Bastian, Jaime R; Chen, Huijun; Zhang, Hongfei; Rothenberger, Scott; Tarter, Ralph; English, Dennis; Venkataramanan, Raman; Caritis, Steve N

    2017-01-01

    Buprenorphine is a Food and Drug Administration-approved maintenance therapy for opioid use disorders and is increasingly being used in pregnant women with opioid use disorders as an alternative to methadone. Dosing of buprenorphine in pregnant women is based on the regimen recommended for nonpregnant females and males. Limited data are available defining the pharmacokinetic properties of sublingual buprenorphine administered during pregnancy. This study evaluated the impact of physiological changes associated with pregnancy on the pharmacokinetics of sublingual buprenorphine during and after pregnancy. Pregnant women (n = 13), between 180/7 and 376/7 weeks' singleton gestation, receiving sublingual buprenorphine twice daily for opioid use disorders were studied. Pharmacokinetic-2 studies were performed between 18 and 25 weeks (n = 7), pharmacokinetic-3 studies were performed between 31 and 37 weeks (n = 11), and pharmacokinetic-P was performed 4-18 weeks postpartum (n = 10). On the day of the study, blood was withdrawn prior to the daily morning dose of buprenorphine and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours after the dose. Buprenorphine plasma concentrations were analyzed by liquid chromatography tandem mass spectrometric detection. All pharmacokinetic parameters were observed or estimated using Microsoft Excel. Statistical analyses were performed to identify significant changes in study participants' buprenorphine pharmacokinetic parameter estimates over the duration of the study. Univariate linear and generalized linear mixed models were used to investigate changes in these measures over time, some of which were log transformed for normality. Dose-normalized (plasma concentration per dose) buprenorphine plasma concentrations were significantly lower during pregnancy (pharmacokinetic-2 plus pharmacokinetic-3) than during the postpartum period (pharmacokinetic-P). Specific pharmacokinetic parameters (and level of significance) were as follows: the

  15. Distinct modulation of allergic T cell responses by subcutaneous versus sublingual allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Schulten, Véronique; Tripple, Victoria; Andersen, Kristian Aasbjerg

    2016-01-01

    mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen allergic patients were randomized into groups receiving either SCIT......: The most dominant immunological changes on a cellular level was a decrease in IL-5 in the SCIT group and a significant, transient increase of IL-10 observed after 10 months of treatment in both treated groups. The distinct routes of AIT administration may induce different immune-modulatory mechanisms...

  16. Fixed-Combination Gels of Adapalene and Benzoyl Peroxide Provide Optimal Percutaneous Absorption Compared to Monad Formulations of These Compounds: Results from Two In Vitro Studies.

    Science.gov (United States)

    Osman-Ponchet, Hanan; Sevin, Karine; Gaborit, Alexandre; Wagner, Nathalie; Poncet, Michel

    2017-03-01

    Adapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) and adapalene 0.3%/BPO 2.5% (0.3% A/BPO) gels are fixed-combination options for the topical treatment of acne. However, the active compounds of these combinations are also available as monads, to be used in association or as monotherapy. These two in vitro studies determined the effect of different treatment regimens on the percutaneous absorption of adapalene (0.1% and 0.3%) gels and BPO 2.5% gel in ex vivo human skin. In vitro percutaneous absorption studies were conducted using full-thickness human skin from six donors. Treatment regimens included the application of 0.1% A/BPO, 0.3% A/BPO, or four free-combination regimens of the monads. Skin samples were incubated for 24 h. Concentrations of adapalene and BPO equivalent (BPO-eq) (i.e. benzoic acid after chemical transformation of BPO) were measured using high-performance liquid chromatography. Comparison of regimens was performed using a bioequivalence criterion (estimated ratio bewteen 0.8 and 1.25). The fixed combination 0.3% A/BPO regimen demonstrated more than three times higher absorption of adapalene versus the fixed-combination 0.1% A/BPO. Based on the bioequivalence acceptance criterion, all four free-combination regimens were different from 0.1% A/BPO and 0.3% A/BPO, with higher adapalene release delivered by the fixed combinations versus the free combinations. For BPO-eq, the results showed that the free-combination regimens where adapalene 0.1% was applied first were different from 0.1% A/BPO, with lower BPO-eq release delivered by these regimens compared to the fixed combination. The regimen adapalene 0.3% for 10 h followed by BPO 2.5% delivered lower BPO-eq release compared to the fixed combination. The fixed-combination A/BPO gels provide optimal percutaneous absorption of the active compounds compared to free combinations of adapalene 0.1%, adapalene 0.3%, and BPO 2.5%. The higher concentration of adapalene in the 0.3% A/BPO gel and the

  17. Evaluation of the efficacy of a combined formulation (Grippostad-C) in the therapy of symptoms of common cold: a randomized, double-blind, multicenter trial.

    Science.gov (United States)

    Koytchev, R; Vlahov, V; Bacratcheva, N; Giesel, B; Gawronska-Szklarz, B; Wojcicki, J; Mrozikiewiczs, A; van der Meer, M; Alken, R G

    2003-03-01

    The aim of the present trial was to evaluate the efficacy of a combined product in the treatment of common cold and to examine the contribution of the separate components. In the published literature there is conflicting data on the efficacy of agents used in the treatment of common cold, especially when given in drug combinations. A prospective, randomized, double-blind, multicenter, 4-arm, controlled trial was carried out in 1,167 patients with common cold treated with one of the following medications: Grippostad-C, a combination of acetaminophen, caffeine, chlorpheniramine and ascorbic acid (verum), ascorbic acid (control), chlorpheniramine and ascorbic acid (reference 1), as well as acetaminophen, caffeine, and ascorbic acid (reference 2). A score of common cold symptoms (headache, throat pain, extremities and joint pain, cough, blocked nose, and disturbances of sleep quality) was the primary outcome. The test drug was first compared with the control using a hierarchic test strategy, then with reference 1, followed by reference 2 with the aim of proving superiority. A clinically relevant and statistically significant difference was demonstrated at each level of the hierarchy. Grippostad-C was significantly superior to all other treatment groups, the combination of acetaminophen, caffeine, and ascorbic acid was significantly superior to the control, and the combination of chlorpheniramine and ascorbic acid was not statistically different from the control. The efficacy of Grippostad-C for the treatment of common cold was proven. The findings demonstrate that the combination is superior to each of its separate components and each of the components has its own distinctive contribution to the efficacy of the combination product.

  18. Congenital hypothyroidism due to ectopic sublingual thyroid gland in Prader-Willi Syndrome: a case report.

    Science.gov (United States)

    Bocchini, Sarah; Fintini, Danilo; Grugni, Graziano; Boiani, Arianna; Convertino, Alessio; Crinò, Antonino

    2017-09-22

    Thyroid gland disorders are variably associated with Prader-Willi syndrome (PWS). Many of the clinical features in newborns with PWS are similar to those found in congenital hypothyroidism (CH). We report a case of a girl with CH and PWS. At the age of 9 months CH caused by an ectopic sublingual thyroid was diagnosed, and hormone replacement therapy was started. In spite of this treatment a decrease in growth velocity, weight excess and delayed development were observed. At the age of 9 years PWS was suspected on the basis of phenotype and genetic tests confirmed a maternal uniparental disomy of chromosome 15. This is the second reported case of hypothyroidism due to an ectopic sublingual thyroid gland in PWS suggesting that, although rare, an association between CH and PWS may exist. In our case diagnosis of PWS was delayed because mental retardation, hypotonia, obesity and short stature were initially attributed to hypothyroidism. In this context PWS should be considered in obese children with CH who do not improve adequately with l-thyroxine therapy. Also, thyroid function in all PWS children should be assessed regularly in order to avoid delayed diagnosis of hypothyroidism.

  19. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    Directory of Open Access Journals (Sweden)

    Luciana Reis AZEVEDO-ALANIS

    2015-10-01

    Full Text Available Although some morphological investigations on aged human sublingual glands (HSG found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated.Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death.Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years; II (31–60, and III (61–90. Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM. Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05.Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001. However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis.Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.

  20. Efficacy of alprazolam sublingual tablets in the treatment of the acute phase of panic disorders.

    Science.gov (United States)

    Márquez, Miguel; Arenoso, Hector; Caruso, Norberto

    2011-01-01

    Panic disorder affects 2-5% of the general population. In Argentina, one million people would be affected with a 91% rate of psychiatric comorbidity. AIM; To compare efficacy parameters between sublingual (ALP-SL) and conventional (ALP-CT) tablets of alprazolam in the treatment of acute phase of panic disorder with and without agoraphobia. A comparative, multicenter (6 sites), double blind, randomized study was carried out. A total of 190 outpatients with (n=117) and without (n=73) agoraphobia were treated with ALP-SL or ALP-CT for 12 weeks. Outcome was assessed with the Clinical Global Impressions (CGI-S/CGI-I), Hamilton Rating Scale for Anxiety (HAM-A), Arizona Sexual Experiences Scale (ASEX), Patient Global Impression (PGI), Psychological General Well-Being Index (PGWBI), Panic Disorder Severity Scale (PDSS) also by the number of panic attacks and extension and intensity of panic attacks and anticipatory anxiety. RESULTS. Both treatments resulted in statistically significant clinical improvement in all measures. ASEX presented no changes during the study. The average dose of alprazolam for 12 weeks was 1.36 ± 0.70 mg/day (1.39 ± 0.77 ALP-CT and 1.33 ± 0.64 ALP-SL). With ALP-SL, panic attacks were shorter (p Alprazolam has been demonstrated to have efficacy, safety and good tolerability in the treatment of the acute phase of panic disorder, the sublingual tablets showing some comparative advantages.

  1. Spontaneous sublingual and intramural small-bowel hematoma in a patient on oral anticoagulation

    Directory of Open Access Journals (Sweden)

    Mohamed Moftah

    2012-08-01

    Full Text Available Spontaneous sublingual hematoma and intramural small bowel hematoma are rare and serious complications of anticoagulant therapy. Though previously reported individually, there has been no previous report of the same two complications occurring in a single patient. A 71-year-old Caucasian man, who was on warfarin for atrial fibrillation, presented with difficulty in swallowing due to a sublingual hematoma. He was observed in our intensive care unit, his warfarin was held and he recovered with conservative management. He represented two months later with a two day history of abdominal pain and distension. An abdominopelvic computed tomography (CT scan now showed small bowel obstruction due to intramural small bowel hematoma and haemorrhagic ascites. Again, this was treated expectantly with a good outcome. In conclusion, life threatening haemorrhagic complications of oral anticoagulant therapy can recur. Conservative treatment is successful in most cases, but an accurate diagnosis is mandatory to avoid unnecessary surgery. CT scan is the investigation of choice for the diagnosis of suspected haemorrhagic complications of over coagulation.

  2. Fixed-Combination Gels of Adapalene and Benzoyl Peroxide Provide Optimal Percutaneous Absorption Compared to Monad Formulations of These Compounds: Results from Two In Vitro Studies

    OpenAIRE

    Osman-Ponchet, Hanan; Sevin, Karine; Gaborit, Alexandre; Wagner, Nathalie; Poncet, Michel

    2016-01-01

    Introduction Adapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) and adapalene 0.3%/BPO 2.5% (0.3% A/BPO) gels are fixed-combination options for the topical treatment of acne. However, the active compounds of these combinations are also available as monads, to be used in association or as monotherapy. These two in vitro studies determined the effect of different treatment regimens on the percutaneous absorption of adapalene (0.1% and 0.3%) gels and BPO 2.5% gel in ex vivo human skin. Methods In...

  3. Maternal immunization with respiratory syncytial virus fusion protein formulated with a novel combination adjuvant provides protection from RSV in newborn lambs.

    Science.gov (United States)

    Garg, R; Latimer, L; Wang, Y; Simko, E; Gerdts, V; Potter, A; van Drunen Littel-van den Hurk, S

    2016-01-04

    Respiratory syncytial virus (RSV) is the causative agent of serious upper and lower respiratory tract infections in newborns and infants. Protection from RSV is crucial for neonates, and maternal immunization is one approach that holds promise for providing immediate protection to young infants against severe RSV infection. We previously reported efficacy of a subunit vaccine consisting of the fusion (F) protein formulated with a novel adjuvant (ΔF/TriAdj) in neonates. The goal of the current study was to evaluate the ΔF/TriAdj as a maternal vaccine. Pregnant ewes were vaccinated intramuscularly with ΔF/TriAdj or PBS six weeks prior to lambing, and re-vaccinated four weeks later, which resulted in transfer of maternal antibodies (MatAbs) to the newborn lambs through the colostrum. Significantly higher levels of RSV ΔF-specific serum IgG were detected in vaccinated pregnant ewes and their lambs when compared to control animals, which revealed that MatAbs were passively transferred to the offspring. All newborn lambs were challenged with RSV at three days of age. After RSV challenge, virus production and lung pathology were significantly lower in lambs that had received passively transferred antibodies than in control animals. These results indicate that maternal immunization with ΔF/TriAdj might be an alternative, safe and effective approach to provide protection against RSV in newborn and young infants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Combining MOSCED with molecular simulation free energy calculations or electronic structure calculations to develop an efficient tool for solvent formulation and selection.

    Science.gov (United States)

    Cox, Courtney E; Phifer, Jeremy R; Ferreira da Silva, Larissa; Gonçalves Nogueira, Gabriel; Ley, Ryan T; O'Loughlin, Elizabeth J; Pereira Barbosa, Ana Karolyne; Rygelski, Brett T; Paluch, Andrew S

    2017-02-01

    Solubility parameter based methods have long been a valuable tool for solvent formulation and selection. Of these methods, the MOdified Separation of Cohesive Energy Density (MOSCED) has recently been shown to correlate well the equilibrium solubility of multifunctional non-electrolyte solids. However, before it can be applied to a novel solute, a limited amount of reference solubility data is required to regress the necessary MOSCED parameters. Here we demonstrate for the solutes methylparaben, ethylparaben, propylparaben, butylparaben, lidocaine and ephedrine how conventional molecular simulation free energy calculations or electronic structure calculations in a continuum solvent, here the SMD or SM8 solvation model, can instead be used to generate the necessary reference data, resulting in a predictive flavor of MOSCED. Adopting the melting point temperature and enthalpy of fusion of these compounds from experiment, we are able to predict equilibrium solubilities. We find the method is able to well correlate the (mole fraction) equilibrium solubility in non-aqueous solvents over four orders of magnitude with good quantitative agreement.

  5. Combining MOSCED with molecular simulation free energy calculations or electronic structure calculations to develop an efficient tool for solvent formulation and selection

    Science.gov (United States)

    Cox, Courtney E.; Phifer, Jeremy R.; Ferreira da Silva, Larissa; Gonçalves Nogueira, Gabriel; Ley, Ryan T.; O'Loughlin, Elizabeth J.; Pereira Barbosa, Ana Karolyne; Rygelski, Brett T.; Paluch, Andrew S.

    2017-02-01

    Solubility parameter based methods have long been a valuable tool for solvent formulation and selection. Of these methods, the MOdified Separation of Cohesive Energy Density (MOSCED) has recently been shown to correlate well the equilibrium solubility of multifunctional non-electrolyte solids. However, before it can be applied to a novel solute, a limited amount of reference solubility data is required to regress the necessary MOSCED parameters. Here we demonstrate for the solutes methylparaben, ethylparaben, propylparaben, butylparaben, lidocaine and ephedrine how conventional molecular simulation free energy calculations or electronic structure calculations in a continuum solvent, here the SMD or SM8 solvation model, can instead be used to generate the necessary reference data, resulting in a predictive flavor of MOSCED. Adopting the melting point temperature and enthalpy of fusion of these compounds from experiment, we are able to predict equilibrium solubilities. We find the method is able to well correlate the (mole fraction) equilibrium solubility in non-aqueous solvents over four orders of magnitude with good quantitative agreement.

  6. Major allergen content consistency of SQ house dust mite sublingual immunotherapy tablets and relevance across geographic regions.

    Science.gov (United States)

    Nolte, Hendrik; Plunkett, Greg; Grosch, Karin; Larsen, Jorgen Nedergaard; Lund, Kaare; Bollen, Mirko

    2016-09-01

    Consistency in composition and potency, particularly regarding major allergens, is crucial for the quality of extracts for allergen immunotherapy. To characterize the major allergen composition of house dust mite (HDM) extracts commercially available in the United States and the SQ HDM sublingual immunotherapy (SLIT) tablet, and to relate the composition to patient sensitization patterns. Der 1/Der 2 ratios were determined in 10,000- and 30,000-AU/mL HDM extracts from 5 US companies and the SQ HDM SLIT-tablet. Allergen content was analyzed by enzyme-linked immunosorbent assay and compared with an in-house reference. Sensitivity toward Der p 1, Der p 2, and Der p 10 was determined in serum from randomly selected subgroups of 220 individuals from North American and European SQ HDM SLIT-tablet trials. Mean Der 1/Der 2 ratios in US HDM extracts ranged from 0.4 to 20.5. For the SQ HDM SLIT-tablet (20 batches), variability did not exceed 12% regarding content of Der f 1 (SD, 11.9%; 95% confidence interval [CI], 0.94-1.06), Der p 1 (SD, 6.1%; 95% CI, 0.97-1.03), and combined Der 2 allergen (SD, 6.4%; 95% CI, 0.97-1.03), indicating a consistent Der 1/Der 2 ratio. High allergen sensitivity frequencies toward Der p 1 and Der p 2 were observed regardless of geographic region. Efficacy of the SQ HDM SLIT-tablet has been demonstrated in 5 clinical trials. The SQ HDM SLIT-tablet has efficacy potential for a broad range of patients because it includes a consistent 1:1 ratio of the 2 major HDM allergens to which individuals were most frequently sensitized across geographic regions. Efficacy has been demonstrated. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Safety, tolerability and clinical efficacy of ultra-rush sublingual immunotherapy among patients suffering from allergic rhinitis.

    Science.gov (United States)

    Balaji, R; Parasuramalu, B G; Chandregowda, B V; Gangaboraiah

    2014-01-01

    Conventional immunotherapy for allergy with 3-5 years of treatment period has poor compliance. Ultra-rush sublingual immunotherapy with a shorter period of treatment can have better compliance. There are very few studies on ultra-rush sublingual immunotherapy all over the world. (1) To determine allergen sensitivity among allergic rhinitis patients. (2) To assess safety, tolerability and clinical efficacy of ultra-rush sublingual immunotherapy. The present study was conducted in Allergy clinic, KIMS Hospital & Research Centre, Bangalore, India from January 2010 to June 2011. After obtaining Institutional Ethics Committee approval, 40 allergic rhinitis patients (according to ARIA guidelines) in the 18-60 years age group who were positive for aeroallergens in skin prick test were recruited for ultra-rush sublingual immunotherapy (20min initial phase and 4-month maintenance phase) and followed for 8 months with symptom and treatment diary. Out of 40 patients, the majority, 36 (90.00%) patients were sensitive to house dust mites. Six patients had seven immediate adverse reactions and seven patients had eight delayed adverse reactions. All subsided without medication or with symptomatic oral medications. All patients tolerated ultra-rush SLIT and there was significant decrease in both symptom-score and treatment received in these patients. Ultra-rush SLIT regimen has excellent safety, tolerability and clinical efficacy among allergic rhinitis patients. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.

  8. Comparing vaginal and sublingual administration of misoprostol for labour induction in women with intra-uterine fetal death.

    NARCIS (Netherlands)

    Geels, Y.P.; Gouberville, M.C. de; Visser, L.; Asten, H.A.G.H. van

    2010-01-01

    The objective of this study was to compare complications and effectiveness of induction after vaginal and sublingual administration of misoprostol for labor induction in women with intra-uterine fetal death (IUFD). In a district hospital in Ghana, 23 women with IUFD who underwent labor induction

  9. The performance of a target-controlled infusion of propofol in combination with remifentanil : A clinical investigation with two propofol formulations

    NARCIS (Netherlands)

    Wietasch, JKG; Scholz, M; Zinserling, J; Kiefer, N; Frenkel, C; Knufermann, P; Brauer, U; Hoeft, A

    Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an IV drug to facilitate safe and reliable administration. In this clinical study we investigated the performance of propofol TCI in combination with remifentanil. Fifty-four adult patients scheduled for general surgery

  10. The efficacy of formulations of triclabendazole and ivermectin in combination against liver fluke (Fasciola hepatica) and gastro-intestinal nematodes in cattle and sheep and sucking lice species in cattle.

    Science.gov (United States)

    Stevenson, C R; Mahoney, R H; Fisara, P; Strehlau, G; Reichel, M P

    2002-11-01

    To assess the efficacy of two formulations of triclabendazole and ivermectin in combination against liver fluke (Fasciola hepatica), gastro-intestinal nematodes and sucking louse species in cattle and sheep. A study of 540 cattle and 428 sheep at 18 sites throughout Victoria and New South Wales was undertaken. At each site, one group of cattle or sheep was treated with a combined formulation (Fasimec Cattle or Fasimec Sheep), another received ivermectin and triclabendazole separately. In trials on lice infestation, an additional group remained untreated. Samples for faecal egg counts were collected on days -7, 0 (treatment day), +7, +14 and +21 after treatment. Lice assessments were carried out on days -7, 0, +7, +14, +28, +42 and +56. Both treatments were highly efficacious (> 98% efficacy) against liver fluke in cattle and sheep, against three sucking lice species of cattle and against gastro-intestinal nematodes in sheep. There was also no significant difference between treatments in efficacy. Against gastro-intestinal nematodes, Fasimec Cattle was significantly (P treatment. Mean efficacy for the Fasimec Cattle and Ivomec/Fasinex 120 groups respectively, was 97.6% and 94.2% on Day +7, 98.9% and 91% on Day +14 and 98.5% and 92.6% on Day +21. The efficacy of Fasimec' Cattle and Fasimec Sheep was at least equal to that of currently registered products (with the same active ingredients) used to control these parasites.

  11. Formulation of the respiratory syncytial virus fusion protein with a polymer-based combination adjuvant promotes transient and local innate immune responses and leads to improved adaptive immunity.

    Science.gov (United States)

    Sarkar, Indranil; Garg, Ravendra; van Drunen Littel-van den Hurk, Sylvia

    2016-09-30

    Respiratory syncytial virus (RSV) causes serious upper and lower respiratory tract infections in newborns and infants. Presently, there is no licensed vaccine against RSV. We previously reported the safety and efficacy of a novel vaccine candidate (ΔF/TriAdj) in rodent and lamb models following intranasal immunization. However, the effects of the vaccine on the innate immune system in the upper and lower respiratory tracts, when delivered intranasally, have not been characterized. In the present study, we found that ΔF/TriAdj triggered transient production of chemokines, cytokines and interferons in the nasal tissues and lungs of BALB/c mice. The types of chemokines produced were consistent with the populations of immune cells recruited, i.e. dendritic cells, macrophages and neutrophils, in the nose-associated lymphoid tissue (NALT), lung and their draining lymph nodes of the ΔF/TriAdj-immunized group. In addition, ΔF/TriAdj stimulated cellular activation with generation of mucosal and systemic antibody responses, and conferred complete protection from viral infection in the lungs upon RSV challenge. The effect of ΔF/TriAdj was short-lived in the nasal tissues and more prolonged in the lungs. In addition, both innate and adaptive immune responses were lower when mice were immunized with ΔF alone. These results suggest that ΔF/TriAdj modulates the innate mucosal environment in both upper and lower respiratory tracts, which contributes to robust adaptive immune responses and long-term protective efficacy of this novel vaccine formulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Field efficacy and safety of an oral formulation of the novel combination anthelmintic, derquantel-abamectin, in sheep in New Zealand

    OpenAIRE

    Little, PR; Hodge, A.; Watson, TG; Seed, JA; Maeder, SJ

    2011-01-01

    AIM: To evaluate the efficacy and safety of the novel anthelmintic combination, derquantel-abamectin, against gastrointestinal nematode populations in sheep, under field-use conditions. METHODS: Controlled faecal egg count reduction tests (FECRT) were conducted in New Zealand in 14 trials, covering a range of geographic locations, farming enterprises, breeds, nematode populations, and anthelmintic-resistance profiles. Enrolled animals were naturally infected with mixed populations of gastroin...

  13. The effect of pre-procedure sublingual nitroglycerin on radial artery diameter and Allen's test outcome - Relevance to transradial catheterization.

    Science.gov (United States)

    Chong, Aun-Yeong; Lo, Ted; George, Sudhakar; Ratib, Karim; Mamas, Mamas; Nolan, James

    2017-07-29

    The radial artery is increasingly used for cardiac procedures, but is a relatively small vessel that is prone to spasm when instrumented. Intra-arterial nitroglycerine has been shown to reduce radial spasm but first requires arterial access. We investigated the effect of pre-procedure sublingual nitroglycerin (NTG) on the diameter of the radial artery in a large cohort of patients. 305 subjects underwent ultrasound measurement of their radial and ulnar arteries in both arms before and after the administration of 800μg of sublingual NTG. The Allen's test was also performed in the subjects prior to and after NTG. Radial artery diameter in this Caucasian study group is larger than that reported for other populations. The administration of sublingual NTG significantly increased the size of the right radial artery from 2.88±0.36mm to 3.36±0.40mm in men and from 2.23±0.37 up to 2.74±0.36mm in women. There were also significant increases in left radial, right and left ulnar artery diameters in males and females with NTG. There was no significant effect of NTG on blood pressure. In all patients with an unfavourable Allen's test, retesting following sublingual NTG resulted in transition to a favourable Allen's. Caucasian populations have larger calibre radial arteries compared to other geographic areas. Sublingual NTG is effective at dilating the radial artery in both men and women. This may make radial artery puncture and cannulation less challenging and should be considered in all patients in the absence of contraindications. The results of Allen's testing are dynamic and its usefulness for screening prior to transradial access is undetermined. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Formulation and antibacterial activity test toothpaste combination of triclosan-extract ethanol of suji leaves (Pleomele angustifolia N.E Brown

    Directory of Open Access Journals (Sweden)

    Elya Zulfa

    2017-12-01

    Full Text Available The suji leaf are generally used by the community as a gargle to remove plaque. Toothpaste is one form of dosage suitable for oral health with triclosan active ingredients, but triklosan is corrosive, resistant to bacteria, and decrease the hormonal system, especially the thyroid hormone. The aim of this research is to know the effect of the addition of variation of the concentration of combination of triclosan-ethanol extracts of suji leaf (T-EESL on toothpaste preparation to the chemical characteristics, antibacterial activity of Streptococcus mutans. The ethanol extract of 70% of suji leaf was obtained by maceration method, then made toothpaste preparation with variation of T-EESL combination of FI (1:0, FII (0,5:0,5, FIII (0:1. Toothpaste was tested chemical physics characteristics (organoleptic, viscosity, pH, and foam power, antibacterial activity test. The test results are analyzed descriptively. Based on the results of the research obtained it can be concluded that the results of testing the physical physics of chemistry showed the results that all toothpaste formulas meet the physical characteristics of chemical toothpaste. T-EESL toothpaste (0.5:0,5 (FII has strong antibacterial activity against Streptococcus mutans so it can be used as an alternative to the existing dosage preparation in the market with triclosan active substance.

  15. Crystallization Formulation Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The Crystallization Formulation Lab fills a critical need in the process development and optimization of current and new explosives and energetic formulations. The...

  16. Post-treatment efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet in adults with grass pollen-induced allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Didier, A; Malling, H-J; Worm, Marcel

    2013-01-01

    Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic rhinoconjunctivitis....

  17. Sublingual tacrolimus administration provides similar drug exposure to per-oral route employing lower doses in liver transplantation: a pilot study.

    Science.gov (United States)

    Solari, S; Cancino, A; Wolff, R; Norero, B; Vargas, J I; Barrera, F; Guerra, J F; Martínez, J; Jarufe, N; Soza, A; Arrese, M; Benitez, C

    2017-05-01

    Per-oral tacrolimus administration is not always practicable. Sublingual administration is a potential alternative, but its feasibility and effectiveness compared with oral route has not been established. To compare tacrolimus drug exposure after sublingual and oral administration in liver transplant recipients. Experimental, open-label, non-randomised, cross-over study. Tacrolimus exposure was evaluated in 32 liver transplant recipients receiving oral administration. 12 h tacrolimus area-under-the-curve (AUC0-12 h ) was calculated using tacrolimus blood concentrations at 0-0.5-1-2-4-6-8-12 hrs post-dose. Recipients were switched to sublingual administration, and dose was adjusted to reach similar trough levels, new AUC0-12 h was calculated. Correlation between AUC0-12 h and trough levels was determined for both oral and sublingual phases. Similar trough levels were accomplished with oral and sublingual administration (6.68 ± 2 ng/mL vs. 6.62 ± 1.9 ng/mL (P = 0.8)). Although concentration 2 h post dose was higher in oral phase (15.36 ± 7.14 vs. 13.18 ± 5.64, P = 0.015), AUC0-12 h was similar in both phases (116.6 ± 34.6 vs. 111.5 ± 36.93 ng/mL* h, P = 0.19). Daily dose of tacrolimus required in sublingual phase was 37% lower than that used in oral phase (P tacrolimus when employing sublingual route. Good correlation between AUC0-12 h and trough levels was observed in sublingual phase (r2 = 0.74). Twenty-two recipients were maintained on sublingual administration after the end of study (mean follow-up: 18.7 ± 5.8 months). No difference in liver function tests or rejection rates was found during follow-up period. Sublingual administration of tacrolimus is feasible and provides similar drug exposure compared with oral administration. In our study, at long-term follow-up, sublingual administration was not associated with liver transplant rejection. © 2017 John Wiley & Sons Ltd.

  18. Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial.

    Science.gov (United States)

    Rosenthal, Richard N; Lofwall, Michelle R; Kim, Sonnie; Chen, Michael; Beebe, Katherine L; Vocci, Frank J

    2016-07-19

    The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion. To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence. Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician. Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks). The primary end point was between-group difference in proportion of responders (≥4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than -0.20 (P buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ∞; P buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio, 13.8; 95% CI, 0.018-0.258; P = .03). Non-implant-related and implant-related adverse events occurred in 48.3% and 23% of the buprenorphine implant group and in 52.8% and 13.5% of participants in the sublingual buprenorphine group, respectively. Among adults with opioid dependence maintaining abstinence with a stable dose of sublingual buprenorphine

  19. Deposition of a model substance, Tc E-HIDA, in the oral cavity after administration of lozenges, chewing gum and sublingual tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Davis, S.S.; Melia, C.D.

    1990-01-01

    The deposition and clearance of a model substance, Tc E-HIDA, in the oral cavity/upper oesophagus and in the stomach after administration of lozenges, chewing gum and sublingual tablets has been followed by gamma scintigraphy in a group of healthy male volunteers. Following administration...... of sublingual tablets, the residence time of the model substance in the oral cavity was significantly longer than following administration of chewing gum. The residence time following administration of lozenges was found to be the shortest....

  20. Analgesic efficacy of an oral transmucosal spray formulation of meloxicam alone or in combination with tramadol in cats with naturally occurring osteoarthritis.

    Science.gov (United States)

    Monteiro, Beatriz P; Klinck, Mary P; Moreau, Maxim; Guillot, Martin; Steagall, Paulo Vm; Edge, Daniel K; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Gauvin, Dominique; Del Castillo, Jérôme Re; Troncy, Eric

    2016-11-01

    To evaluate the analgesic efficacy of meloxicam oral transmucosal spray (OTMS) alone and with tramadol in cats with osteoarthritis (OA). Randomized, blinded study. Fifteen geriatric cats weighing 4.5 ± 1.0 kg. Healthy cats with OA were randomly administered a placebo (every 12 hours orally) and meloxicam OTMS (approximately 0.05 mg kg-1 every 24 hours) (group M, n = 7), or tramadol (3 mg kg-1 every 12 hours orally) and meloxicam OTMS (group TM, n = 8) for 25 days. Evaluations performed before treatment (D0) and at week 3 (W3) consisted of peak vertical force, motor activity and response to mechanical temporal summation of pain (RMTS). Data were analyzed with mixed models and Fisher's exact test. Mean ± standard deviation peak vertical force (percentage of body weight) increased significantly in both groups (p = 0.02), from 47.7 ± 6.5% to 60.5 ± 9.4% in group M, and from 51.8 ± 5.0% to 64.1 ± 6.5% in group TM, with no difference between groups. Motor activity increased in M (from 43 ± 12 to 56 ± 13; p = 0.02), but not in TM. The number of stimulations from RMTS increased in TM only. Cut-off values were reached in a larger number of cats (n = 5) in TM than M (n = 1) (p Meloxicam OTMS had similar effects on peak vertical force, motor activity and pain sensitization as previously reported for oral meloxicam in OA cats. The tramadol-meloxicam combination provided no evident benefit over meloxicam alone, except for central hypersensitivity (assessed with RMTS). Further assessment of the potential toxicity of the combination is required prior to clinical use. Gingival administration was well accepted overall. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  1. Field efficacy and safety of an oral formulation of the novel combination anthelmintic, derquantel-abamectin, in sheep in New Zealand.

    Science.gov (United States)

    Little, P R; Hodges, A; Watson, T G; Seed, J A; Maeder, S J

    2010-06-01

    To evaluate the efficacy and safety of the novel anthelmintic combination, derquantel-abamectin, against gastrointestinal nematode populations in sheep, under field-use conditions. Controlled faecal egg count reduction tests (FECRT) were conducted in New Zealand in 14 trials, covering a range of geographic locations, farming enterprises, breeds, nematode populations, and anthelmintic-resistance profiles. Enrolled animals were naturally infected with mixed populations of gastrointestinal nematodes. All trials included a group treated with derquantel-abamectin, and a negative control group. Nine trials included additional groups each treated with a single- or dual-active oral reference anthelmintic, selected from albendazole, levamisole, albendazole-levamisole, ivermectin, abamectin and moxidectin. A total of 838 animals were enrolled across all trials, and were randomly allocated to treatment groups within blocks defined by faecal nematode egg counts (FEC) pretreatment. On Day 0 derquantel-abamectin was administered orally at 1 ml/5 kg bodyweight (2 mg/kg derquantel, 0.2 mg/ kg abamectin), and each reference anthelmintic was given at the recommended label dose. Faecal samples were collected on Day 14 (+/- 1 day), to determine the percentage reduction in mean FEC for each anthelmintic tested. Larval differentiation was also performed post-treatment, to estimate efficacy at the genus level. Animals were weighed on or before Day 0, and on Day 14 (+/- 1 day) in 13 trials. The efficacy of derquantel-abamectin against mixed strongyle populations was > or =99.2%, based on the percentage reduction in geometric mean FEC. Nematodirus sp. was present in six trials at a level sufficient for efficacy calculations to be conducted; in all cases, the efficacy of derquantel-abamectin was 100%. In those trials where the efficacy of at least one reference anthelmintic was abamectin was 100% effective. In five trials, the mean gain in bodyweight was significantly greater in the

  2. Dust Mite-Induced Perennial Allergic Rhinitis in Pediatric Patients and Sublingual Immunotherapy.

    Science.gov (United States)

    Anderson, Halie M; Wood, Robert A; Busse, William W

    Allergic rhinitis (AR) is a common illness in children and can impair their quality of life. Furthermore, many children remain symptomatic despite maximizing systemic antihistamine and topical therapies. It is at this clinical juncture that immunotherapy may be considered. The efficacy and safety associated with both subcutaneous (SCIT) and sublingual (SLIT) approaches are reviewed and positioned as treatment options for pediatric patients, with specific focus on current literature as it relates to SLIT in children, including those with perennial allergic rhinitis. Although there is more extensive experience with SLIT treatment in Europe, grass and ragweed tablet forms of SLIT are approved in the US. Approaches to the care of pediatric patients with allergic rhinitis are presented. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Influence of sublingual captopril on plasma catecholamine levels during hypertensive emergencies and cold immersion.

    Science.gov (United States)

    Polonia, J J; Monteiro, A; Esteves, A; Cunha, M E; Santos, M L; Coutinho, J; Coelho, J L; Brandao, F A; Cerqueira-Gomes, M

    1988-03-11

    Experimental evidence of captopril-induced inhibition of sympathetic activity, mediated by decrease in angiotensin II production, is presented. The blood pressure, plasma catecholamine, plasma renin activity, and plasma aldosterone responses to a single dose of sublingual captopril in 23 patients with hypertensive emergencies were evaluated. The major correlation found was between the captopril-induced decrease in blood pressure and the decrease in plasma norepinephrine levels (r = 0.57, p less than 0.01). In another 11 hypertensive patients with normal or high renin levels, captopril lowered by 65 percent the increase in plasma norepinephrine induced by cold immersion of the forearm. In both circumstances, plasma renin and aldosterone levels changed in accordance with the expected inhibition of angiotensin converting enzyme activity. These data suggest that, in selected circumstances in hypertensive patients, captopril exhibits a depressive influence on sympathetic activity along with the inhibition of the renin-angiotensin system.

  4. Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl.

    Science.gov (United States)

    Alberts, David S; Smith, Christina Cognata; Parikh, Neha; Rauck, Richard L

    2016-10-01

    To investigate the relationship between effective fentanyl sublingual spray (FSS) doses for breakthrough cancer pain (BTCP) and around-the-clock (ATC) transdermal fentanyl patch (TFP). Adults tolerating ATC opioids received open-label FSS for 26 days, followed by a 26-day double-blind phase for patients achieving an effective dose (100-1600 µg). Out of 50 patients on ATC TFP at baseline, 32 (64%) achieved an effective dose. FSS effective dose moderately correlated with mean TFP dose (r = 0.4; p = 0.03). Patient satisfaction increased during the study. Common adverse event included nausea (9%) and peripheral edema (9%). FSS can be safely titrated to an effective dose for BTCP in patients receiving ATC TFP as chronic cancer pain medication. ClinicalTrials.gov identifier: NCT00538850.

  5. Effect of vasopressin on sublingual microcirculation in a patient with distributive shock.

    Science.gov (United States)

    Dubois, Marc J; De Backer, Daniel; Creteur, Jacques; Anane, Sami; Vincent, Jean-Louis

    2003-06-01

    To assess the sublingual microcirculation in a patient during vasopressin administration for a distributive shock after cardiopulmonary bypass. Case-report in the Department of Intensive Care of a university hospital. A 53 year-old man developed severe distributive shock after cardiac transplant, requiring massive doses of vasopressor agents. Vasopressin administered twice at a dose of 0.02 U/min increased mean blood pressure and allowed partial weaning of other vasopressor drugs. Microcirculatory alterations were assessed by orthogonal polarization spectral technique: 50% and 60% of capillaries were perfused at baseline, and these proportions did not worsen when vasopressin was administered. Despite its strong vasopressor effects vasopressin infusion did not worsen microcirculatory alterations in this patient with distributive shock following cardiac surgery.

  6. A Case of Sublingual Dermoid Cyst: Extending the Limits of the Oral Approach

    Directory of Open Access Journals (Sweden)

    Nobuo Ohta

    2012-01-01

    Full Text Available We present the case of a dermoid cyst with an oral and a submental component in a 21-year-old Japanese woman who presented with complaints of a mass in the oral cavity and difficulty in chewing and swallowing solid foods for about 2 years. MRI shows a 55 × 65 mm well-circumscribed cystic mass extending from the sublingual area to the mylohyoid muscle. Under general anesthesia and with nasotracheal intubation, the patient underwent surgical removal of the mass. Although the cyst was large and extending mylohyoid muscle, intraoral midline incision was performed through the mucosa overlying the swelling and the cyst was separated from the surrounding tissues with appropriate traction and countertraction and successfully removed without extraoral incision. Oral approach in surgical enucleation is useful procedure to avoid cosmetic problems in large and extending mylohyoid muscle cyst.

  7. Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Elionai C. de L.; Mussel, Wagner N.; Resende, Jarbas M.; Yoshida, Maria I., E-mail: mirene@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Instituto de Ciencias Exatas. Departamento de Quimica; Fialho, Silvia L.; Barbosa, Jamile; Fialho, Silvia L. [Fundacao Ezequiel Dias, Belo Horizonte, MG (Brazil)

    2013-04-15

    Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz. (author)

  8. Comparison between effects of intravenous lidocaine and sublingual nifedipine on preventing blood pressure increase in laryngoscopy

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohseni

    2010-06-01

    Full Text Available Gholamreza Mohseni1, Azam Kolyaei2, Morteza Farshchian3, Mansour Rezaei4, Negin Ghadami51Anesthesiologist, assistant professor, 2Anesthetist, 3Orthopedist, assistant professor, 4Biostatistician, assistant professor, 5General practitioner, Kermanshah University of Medical Sciences, Kermanshah, IranIntroduction: Arrhythmia during surgery most frequently occurs during laryngoscopy and intratracheal intubation. Many surgical procedures require intratracheal intubation, which results in hemodynamic changes. These changes in ill patients and patients with limited coronary flow reserve are associated with serious events.Materials and methods: A randomized clinical trial was performed on 124 healthy patients who were elective surgery candidates at Taleghani hospital in Kermanshah. Patients were allocated randomly to each equal group of 62 patients with 95% significance and 90% power of test-retest for sample size. The patients had no history of disease or use of special medications. Drugs commonly used for laryngoscopy and intubation to prevent hemodynamic complications, intravenous lidocaine and sublingual nifedipine, were compared with independent and paired t-tests.Results: This comparison suggested that while the mean age, weight, and sex distribution in our two groups were the same, mean changes in systolic and diastolic blood pressure and heart rate increases in the lidocaine group were 12.6%, 7.5%, and 16.5%, and in the nifedipine group, 17.7%, 11.0%, and 23.5% (P value = 0.0052, 0.189, and 0.0001, respectively. Conclusion: According to the results of our study, intravenous lidocaine is more effective than sublingual nifedipine for preventing hemodynamic changes while performing laryngoscopy or intratracheal intubation.Keywords: hemodynamic changes, laryngoscopy

  9. Sublingual sufentanil, a new opportunity for the improvement of postoperative pain management in Italy.

    Science.gov (United States)

    Sacerdote, P; Coluzzi, F; Fanelli, A

    2016-04-01

    Despite the availability of national and international guidelines, adequate postoperative pain (POP) management is still a challenge in Italy. One of the potential reasons for the high incidence of surgical patients complaining moderate to severe pain is the difficult application of the currently recommended analgesic techniques in clinical practice. In particular, morphine, the most commonly used systemic opioid in the POP treatment, has some unfavorable pharmacodynamic and pharmacokinetic characteristics for POP management, suggesting a potential relevant improvement by using different opioids. Many of sufentanil properties make it particularly suitable for POP control: a high affinity for the µ opioid receptor, the highest therapeutic index compared to any other opioid used in clinical practice and the absence of clinically relevant active metabolites. The elevated potency, together with the high lipophilicity of sufentanil, allow the preparation of a nanotablet, 3 mm of diameter and 0.75 mm of thickness, containing 15 µg of active drug. The sublingual route allows a longer time of drug plasmatic permanence in comparison to IV route, overcoming the need for continuous dosing. The patient-controlled system, considered in the present review, is preprogrammed to deliver one sublingual tablet of sufentanil with a 20-minute lockout period with a radiofrequency identification thumb tag allowing only the patient to activate the on demand button. Phase II and III studies have assessed the efficacy of this system in POP management, showing that it was considered more satisfactory than the IV PCA morphine system by both patients and nurses. The introduction of this simple and innovative system of patient-controlled analgesic administration could represent an opportunity for Italy to update the current practice in POP management.

  10. Uso y abuso del nifedipino por vía sublingual en nuestros sistemas de urgencia

    Directory of Open Access Journals (Sweden)

    Nancy Guinart Zayas

    1998-04-01

    Full Text Available Se observa que el incremento de la prevalencia de pacientes hipertensos en nuestras comunidades, y la implantación del Programa Nacional para el control de la hipertensión arterial, no han podido disminuir la cantidad de pacientes que acuden con cifras altas de su presión arterial a nuestros servicios de urgencia con decisiones terapéuticas indiscriminadas y agresivas. Se ha generalizado el uso del nifedipino sublingual, incluso en pacientes de la tercera edad, lo que produce bajadas bruscas de la presión arterial por disminución en la sensibilidad de los barorreceptores y con ellas una alteración de los mecanismos de autorregulación del flujo hístico. Se señala que las complicaciones producidas no son alarmantes, pero con un uso racional y si se cumplen algunas normas, podrían disminuirse aún másIt is observed that the prevalence increase of hypertensive patients in our communities and the implementation of the National Program for the Hypertension Control have not so far been able to reduce the number of hypertensive patients going to our emergency medical services by applying indiscriminate and aggressive therapeutical methods. The use of sublingual administered nifedipine is extensive even in elderly patients, which may cause a sharp blood pressure drop and also a change in the hystic flow self-regulating mechanisms. It is stressed that complications are not serious but if this drug is more rationally used and some directions are fulfilled, then these complications will be further reduced

  11. COMPARISON OF SUBLINGUAL THERAPEUTIC VACCINE WITH ANTIBIOTICS FOR THE PROPHYLAXIS OF RECURRENT URINARY TRACT INFECTIONS

    Directory of Open Access Journals (Sweden)

    María Fernanda Lorenzo-Gómez

    2015-06-01

    Full Text Available Objective: To evaluate the clinical impact of the prophylactic treatment with sublingual immunostimulation in the prevention of recurrent urinary tract infections (rUTIs compared with the use of antibiotics.Material and Methods: Retrospective cohort study evaluating the clinical records of 669 women with rUTIs; 339 had a 6-month prophylaxis with antibiotics and 360 had a 3-month prophylaxis with a sublingual bacterial preparation (MV 140-Uromune®. The time after the prophylaxis-period until the appearance of a new infection (assessed by uroculture was scored during one year. Absolute risk reduction (ARR and number needed to treat (NNT were also calculated.Results: All patients (100% treated with antibiotics experienced a new UTI during the scoring period of 12 months, being the mean time free of UTI 29 (±38 days. In the group treated with the bacterial preparation, only 35 (9.7% patients experienced UTI in the same period. Kaplan-Meier curves comparing the accumulated survival (disease-free time between both groups were significant (P < 0.0001. ARR was 90.28 % (87.18-93.38 and NNT 1.1 (1.1-1.1.Conclusions: These results suggest that the treatment with the bacterial preparation reduces rUTIs very effectively, arising as an effective strategy to reduce the frequency of rUTIs. It reduces antibiotic consumption, matching the current recommendations due to the raise of antimicrobial resistance. Randomized, double-blind and placebo-controlled, clinical trials are needed to establish more accurately the clinical impact of this bacterial preparation in patients with rUTIs.

  12. [Failure of sublingual immunotherapy to treat latex allergy. A report of a case].

    Science.gov (United States)

    Morfin Maciel, Blanca María; Castillo Morfin, Blanca María

    2008-01-01

    Natural rubber latex has been in widespread use for over a century. Reports of immediate hypersensitivity to latex have increased dramatically since the first case was reported in 1979, specially in persons with cumulative latex exposure. A 13 year old male was referred to our office. He had been wearing orthodontic rubber bands for two years. The previous year he started having itchy, red and watery eyes, with sneezing and runny nose when he was exposed to rubber products. Then he developed oral edema and lip ulcers. Finally, he experienced cough, wheezing, chest tightness and dyspnea. The patient had no history of undergoing surgery, and his mother denied pacifier use. He had no history of fruit and vegetables allergy. Physical examination revealed conjunctival hyperemia, with fine papillary response in the upper tarsal plate, hyaline rhinorrhea, turbinate hypertrophy and perioral ulcers. Skin prick test were positive for latex and Quercus albus. Patch test with latex glove was negative, but positive with rubber tourniquet. Total IgE was 365 UI/mL. Latex-specific IgE testing confirmed the diagnosis. Spirometric values were normal. He started rush sublingual immunotherapy with latex extract. When he had finished, he traveled abroad. At immigration the inspectors examined him with latex gloves. Immediately he developed anaphylaxis, needing urgent medical attention. Although the efficacy and safety of sublingual immunotherapy for latex allergy has been demonstrated, the most effective strategy is complete avoidance of latex-containing products. World Public Health Services must promote the use of synthetic elastomer gloves in airports worldwide.

  13. Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4+CD25+Foxp3+ T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model

    Directory of Open Access Journals (Sweden)

    Takaya Yamada

    2012-01-01

    Full Text Available Sublingual immunotherapy (SLIT has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs, but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN, which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

  14. Efficacy and safety of sublingual fentanyl orally disintegrating tablets in patients with breakthrough pain: multicentre prospective study.

    Science.gov (United States)

    Guitart, Jordi; Vargas, Isabel; De Sanctis, Vicente; Ferreras, Julia; Fuentes, Jose; Salazar, Rafael; Vázquez, Juan M; Folch, Jordi; Moya, Jordi; Ribera, Hermann; Rodelas, Francisco; Tomás, Albert; Arilla, María; Coma, Joan; Aberasturi, Teresa; Sintes, Dolores; Lombán, Ester

    2013-09-01

    The aim of this study was to evaluate the effectiveness and safety of sublingual fentanyl oral disintegrating tablets (sublingual fentanyl ODT) for the treatment of breakthrough pain (BTP), cancer or non-cancer related, in terms of relief of pain intensity, adverse events (AEs) and patient satisfaction, and to further examine the clinical and epidemiological profile of patients with BTP in a clinical setting. A multicentre, prospective, open-label study was conducted in 19 pain units from Catalonia hospitals (Spain) over a 1-month period. Opioid-tolerant adult patients experiencing episodes of BTP intensity >5 on a visual analogue scale (VAS) during the 12-24 h before screening or AEs related to their previous rescue medication for BTP received sublingual fentanyl ODT in the course of routine clinical practice and completed a 30-day study period consisting of five assessment points: days 0 (baseline), 3, 7, 15 and 30. The efficacy was assessed by collecting pain intensity and pain relief data at baseline and at each assessment. AEs were recorded by investigators throughout the study during clinic visits and telephone follow-ups. For all patients, titration was begun with an initial dose of 100 μg. No more than two doses were allowed to treat an episode and patients might wait at least 4 h before treating another BTP episode with sublingual fentanyl ODT. The dose was increased by 100 μg multiples up to 400 μg as needed; and by 200 μg multiples up from 400 to 800 μg, the maximum titration step. A total of 182 patients were enrolled and 177 (97.2 %) completed the study: 37 had breakthrough cancer pain (BTcP) and 145 had breakthrough non-cancer pain (BTncP). The mean pain intensity showed a statistically significant improvement at the first assessment point and at all assessments thereafter (p < 0.0001). At the end of the study, the time lag between administration and first effect of sublingual fentanyl ODT was ≤10 min in 69.0 % (60 % BTcP and 71.2 % BTncP). The

  15. The effect of a topical anaesthetic formulation, systemic flunixin and carprofen, singly or in combination, on cortisol and behavioural responses of Merino lambs to mulesing.

    Science.gov (United States)

    Paull, D R; Lee, C; Colditz, I G; Atkinson, S J; Fisher, A D

    2007-03-01

    lambs of mulesing could be improved by use of a combination of local anaesthetic and long acting non-steroidal anti-inflammatory drug.

  16. Nitroglycerin Sublingual

    Science.gov (United States)

    ... ergotamine (in Cafergot, in Migergot), and methylergonovine (Methergine) heparin; medications for high blood pressure, heart failure, or ... such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant ...

  17. Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate.

    Science.gov (United States)

    Pajno, G B; Vita, D; Parmiani, S; Caminiti, L; La Grutta, S; Barberio, G

    2003-12-01

    Immunotherapy is a recognized treatment for allergic respiratory diseases. To study the usefulness of immunotherapy in combination with optimal pharmacological therapy. Thirty-eight children (8-14 years) suffering from seasonal asthma+/-rhinoconjunctivitis due to Parietaria poorly controlled by anti-allergic drugs treatment were selected. After randomization according to a double-blind placebo-controlled design they received active sublingual immunotherapy (15 children) or placebo (15 children) for 13 months combined with inhaled fluticasone twice a day during the pollen season. Eight children were taken as control, whereas all patients were instructed to take symptomatic drugs on need. Early and late skin response to the allergen were assessed in all patients before and after treatment. Drug and symptom scores, as well as visual analogue scores (VASs) and Parietaria pollen counts were assessed during the pollen season. Groups were well balanced for age, gender, early and late skin response before treatment. Four children dropped out, in one case in relationship with active sublingual immunotherapy (SLIT) administration. Chest and nose symptoms, as well as drug scores and VASs were significantly better in both the active or placebo SLIT+fluticasone (S+F) as compared to the control group (P between <0.001 and 0.043). Eye symptoms were significantly better in the active S+F group as compared to control (P=0.025). The VASs were significantly better in the active S+F group as compared to the placebo S+F group (P=0.037). The early skin response decreased significantly in the active S+F group (P<0.001), whereas the late skin response changed significantly in all groups, with an increase in the placebo+fluticasone group (P=0.019) and in the control group (P=0.037) and a decrease (P<0.0001) in the active S+F group. The clinical efficacy of S+F is equal to that of fluticasone alone, but the addition of SLIT has effects also on non-bronchial symptoms.

  18. The effectiveness of a fixed-dose combination pour-on formulation of 1.25% fipronil and 2.5% fluazuron against economically important ectoparasites and associated pharmacokinetics in cattle.

    Science.gov (United States)

    Lopes, Welber Daniel Zanetti; Chiummo, Rafael Marin; Vettorato, Luis Fernando; de Castro Rodrigues, Daniel; Sonada, Rafael Bazaglia

    2017-10-01

    The present work consisted of eight studies to evaluate the ectoparasiticidal spectrum and determine the pharmacokinetic parameters of a pour-on combination of fipronil 1.25mg/kg+fluazuron 2.5mg/kg for cattle against Rhipicephalus microplus, Haematobia irritans and the larvae of Dermatobia hominis and Cochliomyia hominivorax. The analysis fipronil and fluazuron were performed by liquid chromatography using a mass detector for the detection and quantification of analytes (LC-MS/MS). Additionally, in two of these studies, the animals were artificially infested with R. microplus ticks (stall tests), and the efficacy of this formulation was compared with that of two other standalone pour-on formulations of fipronil 1.0mg/kg and fluazuron 2.5mg/kg. In the two stall studies, 28 calves were artificially infested with 5000 R. microplus (different strains), and daily collections of all of the engorged female ticks that detached from each calf were performed until 60 and 100days post-treatment (dpt). For the R. microplus field trials, 20 bovines were selected by counting the semi-engorged females, and the therapeutic and residual efficacy was evaluated by taking tick counts at 3, 7, 14, 21, 28, 35, 42, 49 and 56dpt. Forty bovines that were naturally infested with Dermatobia hominis larvae were selected, and the numbers of larvae were counted by visual and tactile inspection on 3, 7, 14, 28, 35, 42 and 49dpt. To address the efficacy on C. hominivorax larvae, two circular skin incisions (one on each side of the body) measuring approximately 4cm in diameter each were made in 12 crossbred calves, and the natural exposure of the lesions to C. hominivorax infestations was then allowed. The incisions from the 12 animals were carefully examined daily from 1 to 10dpt. Based on the PK results obtained for this pour-on combination containing fipronil 1.25mg/kg+fluazuron 2.5mg/kg, the maximum concentrations (Cmax) and the half-lives (T1/2) of these two active ingredients were detected

  19. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy

    DEFF Research Database (Denmark)

    Valovirta, Erkka; Petersen, Thomas H; Piotrowska, Teresa

    2017-01-01

    BACKGROUND: Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. OBJECTIVE: The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet...... compared with placebo on the risk of developing asthma. METHODS: A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial......, comprising 3 years of treatment and 2 years of follow-up. RESULTS: There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet...

  20. Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Malling, Hans-Jørgen; Montagut, A; Melac, M

    2009-01-01

    BACKGROUND: The optimal dose of grass pollen tablets for sublingual immunotherapy (SLIT) in allergic rhinoconjunctivitis patients was previously established in a multinational, randomized, double-blind, placebo-controlled study in 628 adults. Patients were randomized to receive once-daily 5-grass...... pollen sublingual tablets of 100 IR (index of reactivity), 300 IR or 500 IR, or placebo starting 4 months before the pollen season. OBJECTIVE: The aim of this complementary analysis was to determine whether 300 IR 5-grass pollen SLIT-tablets is effective in different subtypes of patients who are allergic......: The risk-benefit ratio validates the use of 300 IR tablets in clinical practice in all of these patient subgroups, regardless of severity profile, sensitization status and presence of asthma....

  1. Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation

    Directory of Open Access Journals (Sweden)

    Nicolini Gabriele

    2011-07-01

    Full Text Available Abstract Background Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS and long acting beta-agonists (LABA. Methods This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits. Results 111 patients were analyzed: 53 (47.7% received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F pressurized metered dose inhaler (pMDI, 25 (22.5% fluticasone-salmeterol (FP/S dry powder inhaler (DPI, and 33 (29.7% budesonide-formoterol (BUD/F DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively and the mean daily ICS dose were significantly lower. Conclusions pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both.

  2. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis.

    Science.gov (United States)

    Durham, Stephen R; Yang, William H; Pedersen, Martin R; Johansen, Niels; Rak, Sabina

    2006-04-01

    Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases. Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events. To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis. A multinational, multicenter, randomized, placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX; ALK-Abelló, Hørsholm, Denmark) or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks. Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T (P = .0710; P = .0470) compared with placebo. Significantly better rhinoconjunctivitis quality of life scores (P = .006) and an increased number of well days (P = .041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication use, 29%, P = .0120). No safety concerns were observed. This study confirms dose-dependent efficacy of the grass allergen tablet. Although further studies are required, the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy. For patients with grass pollen allergy, sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life.

  3. Sublingual targeting of STING with 3'3'-cGAMP promotes systemic and mucosal immunity against anthrax toxins.

    Science.gov (United States)

    Martin, Tara L; Jee, Junbae; Kim, Eunsoo; Steiner, Haley E; Cormet-Boyaka, Estelle; Boyaka, Prosper N

    2017-04-25

    Anthrax is caused by Bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. The current human anthrax vaccine, anthrax vaccine adsorbed (AVA), is an injected vaccine with a cumbersome administration schedule and fails to promote mucosal immunity. Bacterial enterotoxins, which stimulate production of the cyclic nucleotide cAMP are effective experimental mucosal vaccine adjuvants, but their inherent toxicity has precluded their use in humans. We investigated whether cyclic dinucleotides that target Stimulator of Interferon Gamma Genes (STING) in mammalian cells could represent an alternative to bacterial enterotoxins as adjuvant for sublingual immunization and promotion of mucosal immunity and secretory IgA responses in addition to systemic immunity. We found that sublingual immunization of mice with Bacillus anthracis protective antigen (PA) and the STING ligand 3'3'-cGAMP promotes PA-specific serum IgG Ab responses of the same magnitude as those induced after immunization with PA and the experimental adjuvant cholera toxin (CT). Interestingly, this STING ligand also promoted serum anti-PA IgA and IgA-producing cells in the bone marrow. Furthermore, the saliva of mice immunized with the STING ligand exhibited similar levels of PA-specific IgA Abs as groups immunized with CT as adjuvant. The adjuvant activity of 3'3'-cGAMP was associated with mixed Th1, Th2, and Th17 responses. This STING ligand also induced rapid IFN-β and IL-10 responses in sublingual tissues and cervical lymph nodes, and TGF-β responses in the cervical lymph nodes, which could contribute to promoting IgA responses after sublingual immunization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis

    OpenAIRE

    Meadows, A.; Kaambwa, B.; Novielli, N.; Huissoon, A.; Fry-Smith, A; Meads, C; P. Barton; Dretzke, J

    2013-01-01

    © Queen’s Printer and Controller of HMSO 2013 Severe allergic rhinitis uncontrolled by conventional medication can substantially affect quality of life. Immunotherapy involves administering increasing doses of a specific allergen, with the aim of reducing sensitivity and symptomatic reactions. Recent meta-analyses have concluded that both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are more effective than placebo in reducing symptoms. It is uncertain which route o...

  5. FORMULASI MIKROEMULSI MINYAK DALAM AIR (O/W YANG STABIL MENGGUNAKAN KOMBINASI TIGA SURFAKTAN NON IONIK DENGAN NILAI HLB RENDAH, TINGGI DAN SEDANG Stable O/W Microemulsion Formulation Using Combination of Three Nonionic Surfactants with Low, High and Med

    Directory of Open Access Journals (Sweden)

    Sih Yuwanti

    2012-05-01

    Full Text Available The aim of this research was to determine the proportion of oil, surfactant and water which could produce a stable O/W microemulsion using combination of three nonionic surfactants with low, high and medium HLB values; and to determine the role of surfactant with a medium HLB value in O/W microemulsion formulation. The first group of microemulsions were prepared using combination of Tween 80, Span 80 and Span 40 (80 %:10 %:10 % with dif- ferent proportions of VCO:surfactant (1:3, 1:3.5 dan 1:4.  The second goups of microemulsion were prepared using combination of Tween 80, Span 80 and Span 40 (90 %:5 %:5 % with different proportions of VCO:surfactant 1:4,1:4.5 dan 1:5.  The stability of microemulsion was determined during storage at room temperature and after being ovened at 105 0C 5 hours and centrifuged at 2300 g 15 minutes. Microemulsion stability was determined by measur- ing absorbance of the microemulsion at 502 nm and then converted to turbidity (%.  In order to determine the role of surfactant with a medium HLB value in the formulation of O/W microemulsion, one set microemulsions were made without surfactant with a medium HLB value, and another set of microemulsions were prepared with different ratios of low and medium HLB surfactant (1:1, 2:1 and 1:2. The most stable microemulsion was achieved when the proportion of VCO:surfactant:water was 4:20:76 and combination of Tween 80:Span 80:Span 40 with the ratio of 90:3.33:6.67. A more stable O/W microemulsion could be obtained when surfactant with a medium HLB value was added to O/W microemulsion formulation. Surfactant with a medium HLB value would link the oil phase and water phase with sur- factant layer, interaction of surfactant-oil and surfactant-water increased. It provided a smooth transition between oil phase and water phase, and the microemulsion became more stable. ABSTRAK Tujuan dari penelitian ini adalah untuk menentukan proporsi minyak, surfaktan dan air yang dapat

  6. Recombinant Mal d 1 facilitates sublingual challenge tests of birch pollen-allergic patients with apple allergy.

    Science.gov (United States)

    Kinaciyan, T; Nagl, B; Faustmann, S; Kopp, S; Wolkersdorfer, M; Bohle, B

    2016-02-01

    It is still unclear whether allergen-specific immunotherapy (AIT) with birch pollen improves birch pollen-related food allergy. One reason for this may be the lack of standardized tests to assess clinical reactions to birch pollen-related foods, for example apple. We tested the applicability of recombinant (r) Mal d 1, the Bet v 1-homolog in apple, for oral challenge tests. Increasing concentrations of rMal d 1 in 0.9% NaCl were sublingually administered to 72 birch pollen-allergic patients with apple allergy. The dose of 1.6 μg induced oral allergy syndromes in 26.4%, 3.2 μg in 15.3%, 6.3 μg in 27.8%, 12.5 μg in 8.3%, 25 μg in 11.1%, and 50 μg in 4.2% of the patients. No severe reactions occurred. None of the patients reacted to 0.9% NaCl alone. Sublingual administration of 50 μg of rMal d 1 induced no reactions in three nonallergic individuals. Our approach allows straight forward, dose-defined sublingual challenge tests in a high number of birch pollen-allergic patients that inter alia can be applied to evaluate the therapeutic efficacy of birch pollen AIT on birch pollen-related food allergy. © 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.

  7. Role of BAFF in pediatric patients with allergic rhinitis during sublingual immunotherapy.

    Science.gov (United States)

    Luo, Renzhong; Liu, Wenlong; Wang, Jie; Chen, Yanqiu; Sun, Changzhi; Zhou, Lifeng; Li, Yan; Deng, Li

    2014-08-01

    Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic rhinitis (AR) that modifies the immunological process to an allergen, rather than treating symptoms simply. However, its regulatory mechanisms are largely unknown. B-cell-activating factor of the TNF family (BAFF) plays very important roles in the development, differentiation, and proliferation of B cells and T cells. The aim of this study was to identify the role of BAFF during SLIT in pediatric patients with AR. Seventy-two house dust mite (HDM)-sensitized pediatric patients with AR were enrolled in this study. Thirty-six pediatric patients received HDM allergen extract for SLIT and 36 pediatric patients received placebo. Serum and nasal aspirate of different time points during treatment was collected and used for enzyme-linked immunosorbent assay (ELISA) of BAFF and related cytokines, respectively. Peripheral blood mononuclear cells were collected and stimulated by HDM allergen with or without rhBAFF after 12 months of treatment. Our results showed that the expression of BAFF protein decreased during the SLIT treatment compared with that in the placebo group after 6 months of therapy, and this trend lasted for 12 months. The decreased BAFF expression was positively related to Th2 cytokines and increased IL-10 expression. BAFF was also related to local production of IgA. In vitro experiments showed that BAFF can promote Th2 cytokines and inhibit IL-10 expression by PBMCs. During SLIT, BAFF expression was decreased and related to low Th2 cytokine expression and enhanced IL-10 expression. Besides, BAFF may contribute to local production of IgA. Our results suggested that BAFF may be an important biomarker during SLIT. Authors' summary. Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic rhinitis (AR) that modifies the immunological process to an allergen, rather than simply treating symptoms. However, its regulatory mechanisms are largely unknown. B

  8. Efficacy and safety of two fast-absorbing formulations of paracetamol in combination with caffeine for episodic tension-type headache: results from two randomized placebo- and active-controlled trials

    Directory of Open Access Journals (Sweden)

    Yue Y

    2017-06-01

    Full Text Available Yong Yue,1 Kenneth D Reed,1 Lucy Shneyer,2 Dongzhou J Liu3 1GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, 2Shneyer Statistics LLC, Denville, NJ, 3GlaxoSmithKline, Collegeville, PA, USA Objectives: Two randomized placebo-controlled trials evaluated whether combining rapid-acting paracetamol formulations with caffeine resulted in faster/greater relief of episodic tension-type headache (ETTH compared with placebo and over-the-counter (OTC analgesics. Both studies were prematurely terminated. Materials and methods: In the single-blind crossover study 1, adults with ETTH (n=66 received three of the following in random sequence: paracetamol 1,000 mg with sodium bicarbonate 650 mg and caffeine 130 mg; paracetamol 1,000 mg; ibuprofen 400 mg; and placebo. In the double-blind parallel-group study 2, adults with ETTH (n=157 were randomly assigned 2:2:1 to treat up to three headaches with paracetamol with Optizorb technology 1,000 mg plus caffeine 130 mg; ibuprofen 400 mg; and placebo. Results: In study 1, the primary outcome – mean time to perceptible pain relief – was 36.7, 38, 48.9, and 42.7 minutes in the paracetamol–sodium bicarbonate–caffeine, ibuprofen, paracetamol, and placebo groups, respectively; differences were not statistically significant. In study 2, the weighted sum of pain intensity (scale of 0 [no pain] to 4 [severe pain] difference from the time of treatment to hour 4, the primary outcome, showed numerically favorable differences for paracetamol with Optizorb–caffeine compared with ibuprofen (difference in least square means −0.3, 95% confidence interval −1.05 to 0.45 and placebo (−0.47, 95% confidence interval −1.36 to 0.42. In both studies, secondary outcomes suggested faster and greater relief with rapid paracetamol–caffeine compared with placebo and paracetamol; a few of these outcomes achieved statistical significance at ~45–90 minutes in study 1. Adverse events were mostly mild and consistent with known

  9. Sublingual immunotherapy in asthma and rhinoconjunctivitis; systematic review of paediatric literature

    Science.gov (United States)

    Miceli, S; Macchiaiolo, M; Zorzi, G; Tripodi, S

    2004-01-01

    Aims: To evaluate the clinical efficacy of sublingual immunotherapy (SLIT) in respiratory allergy in children. Methods: A systematic literature review was conducted. The search was focused on all the double blind (and double dummy if necessary) studies. Search strategy: Medline, Embase, Cochrane Controlled Trial Register, Abstract of Cochrane Airways Group, hand search, and archives of some SLIT producers. All the selected studies were assessed and evaluated for quality in a standardised independent way. Results: Eight randomised, double blind, placebo controlled studies on SLIT were selected. Five studies were run with house dust mite (HDM), one with olive pollen, one with wall pellitory (Parietaria) pollen, and one with grass pollen. A quantitative evaluation of the studies was not possible because the outcomes and the results of single studies were presented according to different criteria. Therefore only qualitative analysis was performed. No clinically relevant results were shown, independently from statistical significance, in the use of SLIT for respiratory allergies due to seasonal allergens (olive, wall pellitory, and grass pollens) and, on the whole, for rhinoconjunctivitis due to HDM in children. For mild to moderate persistent asthma due to HDM, statistically significant and low to moderate relevant clinical effects were observed. Conclusions: SLIT can be currently considered to have low to moderate clinical efficacy in children of at least 4 years of age, monosensitised to HDM, and suffering from mild to moderate persistent asthma. This benefit seems to be adjunctive with respect to the environmental preventive measures against HDM. PMID:15210490

  10. The Proteomes of Human Parotid and Submandibular/Sublingual Gland Salivas Collected as the Ductal Secretions

    Science.gov (United States)

    Denny, Paul; Hagen, Fred K.; Hardt, Markus; Liao, Lujian; Yan, Weihong; Arellanno, Martha; Bassilian, Sara; Bedi, Gurrinder S.; Boontheung, Pinmannee; Cociorva, Daniel; Delahunty, Claire M.; Denny, Trish; Dunsmore, Jason; Faull, Kym F.; Gilligan, Joyce; Gonzalez-Begne, Mireya; Halgand, Frédéric; Hall, Steven C.; Han, Xuemei; Henson, Bradley; Hewel, Johannes; Hu, Shen; Jeffrey, Sherry; Jiang, Jiang; Loo, Joseph A.; Ogorzalek Loo, Rachel R.; Malamud, Daniel; Melvin, James E.; Miroshnychenko, Olga; Navazesh, Mahvash; Niles, Richard; Park, Sung Kyu; Prakobphol, Akraporn; Ramachandran, Prasanna; Richert, Megan; Robinson, Sarah; Sondej, Melissa; Souda, Puneet; Sullivan, Mark A.; Takashima, Jona; Than, Shawn; Wang, Jianghua; Whitelegge, Julian P.; Witkowska, H. Ewa; Wolinsky, Lawrence; Xie, Yongming; Xu, Tao; Yu, Weixia; Ytterberg, Jimmy; Wong, David T.; Yates, John R.; Fisher, Susan J.

    2009-01-01

    Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications—914 in parotid and 917 in submandibular/sublingual saliva—were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes ranging from structural functions to enzymatic/catalytic activities. As expected, the majority mapped to the extracellular and secretory compartments. An immunoblot approach was used to validate the presence in saliva of a subset of the proteins identified by mass spectrometric approaches. These experiments focused on novel constituents and proteins for which the peptide evidence was relatively weak. Ultimately, information derived from the work reported here and related published studies can be used to translate blood-based clinical laboratory tests into a format that utilizes saliva. Additionally, a catalogue of the salivary proteome of healthy individuals allows future analyses of salivary samples from individuals with oral and systemic diseases, with the goal of identifying biomarkers with diagnostic and/or prognostic value for these conditions; another possibility is the discovery of therapeutic targets. PMID:18361515

  11. Innovations and Challenges by Applying Sublingual Laser Blood Irradiation in Juvenile Idiopathic Arthritis

    Directory of Open Access Journals (Sweden)

    Laura Marinela Ailioaie

    2014-01-01

    Full Text Available Sublingual laser blood irradiation (SLBI was applied into a randomized, single-blind, placebo-controlled study in juvenile idiopathic arthritis (JIA, aimed at inducing disease remission. 105 children with JIA, without an adequate response to classical treatment, were administrated a disease modifying drug (Methotrexate and were randomly assigned to three groups. Group I (36 patients received SLBI with the Weberneedle Lasershower Mouth Applicator with three wavelengths (635 nm, 536 nm, and 405 nm, 5 mW maximum output power each, in continuous mode, simultaneously, for 20 minutes daily, 7 successive sessions per month, repeated every 7 weeks, for three times. Group II (36 patients received placebo SLBI. Group III (33 patients received only treatment with Methotrexate. Evaluation was performed using American College of Rheumatology Pediatric criteria (ACR Pedi at study enrollment and at 8, 16, 24, and 48 weeks. At the end of study, there was an improvement of the ACR Pedi 30 by 86.11% in SLBI group compared to only 61.11% in Group II, respectively, and 60.6% in Group III (P=0.001, with significant statistical differences. SLBI has reduced the pain, lowered the number of articulations with movement limitation, increased the quality of life, and made it possible to avoid the administration of biological agents.

  12. Sublingual immunotherapy for house dust mite allergy in Southeast Asian children.

    Science.gov (United States)

    Lee, Melissa; Lee, Bee Wah; Vichyanond, Pakit; Wang, Jiu-Yao; Bever, Hugo Van

    2013-09-01

    To determine the use and efficacy of sublingual immunotherapy (SLIT) for house dust mite (HDM) allergies in Southeast Asian children. Aliterature search was performed in Pubmed and the Asian Pacific Journal of Allergy and Immunology. We also evaluated the literature for similar studies performed in Asia. Clinical trials involving children that assess SLIT for HDM allergies in Southeast Asia and Asia. There are no published studies on the use of SLIT for HD Mallergies in Southeast Asian children. However, there are seven studies from Asia which show that there are discrepancies over the benefits of SLIT for HDM allergies in Asian children. Limitations in these studies include small sample sizes and short study periods. We cannot say with certainty what the impact of SLIT is on HDM allergies in Southeast Asian children due to the lack of data. The available studies performed in Asia have their limitations but are suggestive of the potential of SLIT for HDM allergies in Southeast Asian children. This review highlights that good quality clinical research in this area in the Southeast Asian setting is warranted.

  13. The use of sublingual fentanyl for breakthrough pain by using doses proportional to opioid basal regimen.

    Science.gov (United States)

    Mercadante, Sebastiano; Prestia, Giovanna; Casuccio, Alessandra

    2013-11-01

    The aim of this study was to prospectively assess the efficacy and safety of sublingual fentanyl (SLF) in doses proportional to opioid doses used for background analgesia for the treatment of BTP of cancer patients. A sample of patients admitted to an acute palliative care unit, presenting breakthrough pain (BTP) episodes and receiving stable doses of opioids for background pain was selected to assess the efficacy and safety of SLF used in doses proportional to the basal opioid regimen used for the management of BTP. For each patient, data from four consecutive episodes were collected. For each episode, nurses collected changes in pain intensity and adverse effects when pain got severe (T0), and 5, 10, and 15 minutes after SLF was given (T15). Seventy patients were recruited for the study. The mean age was 61.7 (±11.5). Forty-one patients were males. A total of 173 episodes of BTP were recorded (mean 2.5 episodes/patient). In 19 events, documentation regarding changes in pain intensity was incomplete. Of the 154 evaluable episodes, 143 were successfully treated (92%). Mean doses of SLF were 637 µg (SD 786), and 51 patients (72.8%) received SLF doses ≥800 µg. When compared to younger adult patients, older patients received significantly lower doses of SLF (p opioid regimen. Pain intensity significantly decreased at T5, 10 and T15 (p opioid regimen for the management of BTP is safe and effective in clinical practice.

  14. Sublingual-oral rush desensitization to mixed cow and sheep milk: a case report.

    Science.gov (United States)

    Nucera, E; Schiavino, D; Buonomo, A; Pollastrini, E; Altomonte, G; Pecora, V; Decinti, M; Lombardo, C; Patriarca, G

    2008-01-01

    We attempted an oral rush desensitization with mixed cow and sheep milk in a 6-year-old boy who had had adverse reactions to cow and goat milks. Skin prick tests and specific immunoglobulin (Ig) E to cow, sheep and goat milks were positive. The double-blind, placebo-controlled food challenge with cow milk was positive too. He underwent a 12-day sublingual-oral desensitization treatment with mixed cow and sheep milk. Specific IgE and IgG4 were measured. Open oral challenges with cow milk, sheep milk and sheep cheeses were also performed after the desensitization. At the end of the desensitizing treatment our patient could tolerate 120 mL of mixed milk. Specific IgE levels did not vary, whereas an increase of specific IgG4 concentrations was observed. Open oral challenges with cow and sheep milks and sheep cheeses were negative. Oral rush desensitization may represent an alternative approach to the treatment of food allergy in children.

  15. Ranking in importance of allergen extract characteristics for sublingual immunotherapy by Italian specialists.

    Science.gov (United States)

    Canonica, Giorgio Walter; Passalacqua, Giovanni; Incorvaia, Cristoforo; Cadario, Gianni; Fiocchi, Alessandro; Senna, Gianenrico; Rossi, Oliviero; Romano, Antonino; Scala, Enrico; Romano, Catello; Ingrassia, Antonino; Zambito, Marcello; Dell'Albani, Ilaria; Frati, Franco

    2014-01-01

    The efficacy of allergen immunotherapy (AIT) is well supported by evidence from trials and meta-analyses. However, its actual performance in daily practice may be diminished by several pitfalls, including inappropriate patient selection, and, especially, the use of allergen extracts of insufficient quality. We performed a survey, the Allergen Immunotherapy Decision Analysis, to evaluate which criteria specialists use to choose products for sublingual immunotherapy (SLIT) in adult patients suffering from allergic respiratory disease. We surveyed a total of 169 Italian allergists randomly chosen from a database belonging to a market research company (Lexis Ricerche, Milan, Italy). The survey was performed between October and November 2012 under the aegis of the European Center for Allergy Research Foundation and consisted of a questionnaire-based electronic survey prepared by a scientific board of 12 AIT experts. The questionnaire comprised two parts, the first of which contained 14 items to be ranked by each participant according to the importance assigned to each when choosing SLIT products. The physicians' rankings assigned major importance to the level of evidence-based validation of efficacy and safety, standardization of the product, efficacy based on personal experience, and defined content(s) of the major allergen(s) in micrograms. The results of this survey show that Italian allergists rank the quality-related characteristics of allergen extracts as highly important when choosing products for AIT. The allergists' preference for high-quality products should be addressed by regulatory agencies and by producers.

  16. [Breakthrough pain treatment with sublingual fentanyl in patients with chronic cutaneous ulcers].

    Science.gov (United States)

    Domingo-Triadó, V; López Alarcón, M D; Villegas Estévez, F; Alba Moratillas, C; Massa Domínguez, B; Palomares Payá, F; Mínguez Martí, A; Debón Vicent, L

    2014-10-01

    The aim of the study was to assess the efficacy and safety of opioids in the management of pain in those patients with chronic cutaneous ulcers and breakthrough/incidental pain. An open-label, multicentre, prospective, uncontrolled study was conducted in the pain and ulcer units of 5 hospitals across the Comunidad Valenciana. Eligibility criteria were baseline pain 4 in the visual analogue scale or breakthrough procedural pain 4. Exclusion criteria were cognitive impairment, opioid intolerance, or patient refusal to provide informed consent. The protocol scheduled 5 controls: baseline (enrolment), 15 days, one month, 2 months, and 3 months. The main outcome measure of the study was the visual analogue scale score during rest, movement and procedures. Opioids were administered for release of the baseline pain, and sublingual fentanyl for breakthrough pain. A total of 32 patients (86.5%) completed the study. Baseline pain achieved a mean improvement of 3.6 visual analogue scale points (SD 2.3), movement pain improved by 3.9 points (SD 2.5) and procedural pain improved by 4.5 points (SD 2.8), and the mean pain intensity improvement was statistically significant from the first control and at all controls thereafter (PDolor. Published by Elsevier España. All rights reserved.

  17. Specific IgE response to different grass pollen allergen components in children undergoing sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    Marcucci Francesco

    2012-06-01

    Full Text Available Abstract Background Grass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized. Methods We investigated in 30 children (19 males and 11 females, mean age 11.3 years, 19 treated with sublingual immunotherapy (SLIT by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components. Results Significant increases (p  Conclusions These findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure.

  18. Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells.

    Science.gov (United States)

    Scadding, G W; Shamji, M H; Jacobson, M R; Lee, D I; Wilson, D; Lima, M T; Pitkin, L; Pilette, C; Nouri-Aria, K; Durham, S R

    2010-04-01

    The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT). To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB). Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebo-treated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-beta mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT. Foxp3(+) cells were increased in the oral epithelium of SLIT- vs. placebo-treated atopics (P=0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P=0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT- compared with placebo-treated atopics (P=0.1 for both). IgG(1) and IgG(4) were increased following SLIT (Ppollen extract is associated with increased Foxp3(+) cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.

  19. Confocal laser scanning microscopic analysis of ectopic sublingual gland-like tissue inside the hamster submandibular gland.

    Science.gov (United States)

    Moriguchi, Keiichi; Utsumi, Michiya; Ohno, Norikazu

    2013-12-01

    Based on its histochemical properties, the secretory portion of the hamster submandibular gland has been classified as seromucous cells. The presence of endogenous peroxidase (PO) reaction was shown in the nuclear envelope, cisternae of endoplasmic reticulum and Golgi apparatus. The 3,3'-diaminobenzidene, tetrahydrochloride (DAB) method revealed bipartite secretory granules containing a PO-positive dense core surrounded by a less dense halo in these cells. In the present investigation, serous and mucous-like cells were found in resin-embedded semi-thin sections of the DAB-reacted hamster submandibular gland. These sections were already on glass slides for routine light microscopic observations, therefore electron microscopic analysis could be unrealizable. We then used reflectance-mode confocal laser scanning microscopy to visualize additional sites of PO activity as detected in these sections. Using this approach, we found mucous cells with PO activity-negative secretory granules and seromucous cells with PO activity-positive spot-like secretory granules of the regular sublingual gland most frequently adjacent to the serous cells with typical electron-dense secretory granules. These cells clearly differ from the seromucous cells with bipartite secretory granules and the granular duct cells with typical electron-dense secretory granules of the hamster submandibular gland. Additionally, secretory endpieces of the ectopic sublingual gland-like tissue empty into the duct of the hamster submandibular gland lobule. Thus, our findings suggest that a mass of sublingual gland tissue extends into the hamster submandibular gland during its development, and PO may be synthesized and secreted into the same duct. Copyright © 2013 Wiley Periodicals, Inc.

  20. Crushed sublingual versus oral ticagrelor administration strategies in patients with unstable angina. A pharmacokinetic/pharmacodynamic study.

    Science.gov (United States)

    Niezgoda, Piotr; Sikora, Joanna; Barańska, Malwina; Sikora, Adam; Buszko, Katarzyna; Siemińska, Emilia; Marszałł, Michał Piotr; Siller-Matula, Jolanta M; Jilma, Bernd; Alexopoulos, Dimitrios; Fabiszak, Tomasz; Kubica, Jacek

    2017-04-03

    Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina. Ticagrelor and its metabolite AR-C124900XX plasma concentration was evaluated in nine time points (time frame of 6 hours) using liquid chromatography coupled with mass spectrometry; platelet reactivity was evaluated using multiple electrode aggregometry. The area under the plasma concentration-time curve for ticagrelor and AR-C124900XX was significantly higher in patients treated with crushed tablets given orally compared with crushed tablets given sublingually only within the first hour after loading dose (936.9 ± 898.0 vs 368.0 ± 422.4, p=0.042 and 103.4 ± 120.8 vs 31.3 ± 43.9, p=0.031, respectively). Moreover, we showed significantly stronger platelet inhibition in patients receiving crushed ticagrelor orally vs. sublingually at 30 and 45 min after the loading dose (p=0.024 and p=0.016, respectively). Therefore, the administration strategy of ticagrelor determines the pharmacokinetic and pharmacodynamic profile of both ticagrelor and its active metabolite AR-C124900XX.

  1. Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: a randomised trial.

    Science.gov (United States)

    Parry-Strong, Amber; Langdana, Fali; Haeusler, Sylvan; Weatherall, Mark; Krebs, Jeremy

    2016-06-10

    MAIM: To compare a single 1mg intramuscular hydroxocobalamin injection with a 3-month course of 1mg/day sublingual methylcobalamin supplements on serum vitamin B12 concentrations in participants withtype 2 diabetes treated with metformin. Participants on metformin treatment with vitamin B12 concentrations below 220pmol/L were recruited through hospital diabetes clinics and primary care practices. They were randomised to receive either the injection or sublingual treatment. The primary outcome was serum vitamin B12 level after 3 months adjusted for baseline assessed by analysis of covariance (ANCOVA). The trial was registered on the Australia New Zealand Clinical Trial registry (ACTRN12612001108808). A total of 34 participants were randomised; 19 to the tablet, and 15 to the injection. The mean (SD) age, duration of diabetes, and duration of metformin use were, 64.2 (7.3) years, 13.7 (6.4) years, and 11.6 (5.0) years, respectively. After 3 months, the mean (SD) vitamin B12 was 372.1 (103.3) pmol/L in the tablet group (n=19) compared to 251.7 (106.8) pmol/L in the injection group (n=15), ANCOVA estimated difference -119.4 (95% CI -191.2 to -47.6), p=0.002. After 6 months, the mean (SD) serum B12 was 258.8 (58.7) pmol/L in the tablet group (n=17) and 241.9 (40.1) pmol/L in the injection group (n=15); ANCOVA estimated difference -15.2 (95% CI -50.3 to 19.8), p=0.38. Higher metformin dose was associated with lower serum B12 at 3 months, but not at baseline or 6 months. Decreased serum vitamin B12 level in patients with type 2 diabetes who are treated with metformin can be corrected through treatment with either hydroxocobalamin injections or methylcobalamin sublingual supplements.

  2. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy.

    Science.gov (United States)

    Valovirta, Erkka; Petersen, Thomas H; Piotrowska, Teresa; Laursen, Mette K; Andersen, Jens S; Sørensen, Helle F; Klink, Rabih

    2017-07-06

    Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet compared with placebo on the risk of developing asthma. A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial, comprising 3 years of treatment and 2 years of follow-up. There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial (odds ratio = 0.66, P year posttreatment follow-up, and during the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms were 22% to 30% reduced (P years). At the end of the trial, the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27% relative difference to placebo, P < .001). Total IgE, grass pollen-specific IgE, and skin prick test reactivity to grass pollen were all reduced compared to placebo. Treatment with the SQ grass sublingual immunotherapy tablet reduced the risk of experiencing asthma symptoms and using asthma medication, and had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Explosive Formulation Pilot Plant

    Data.gov (United States)

    Federal Laboratory Consortium — The Pilot Plant for Explosive Formulation supports the development of new explosives that are comprised of several components. This system is particularly beneficial...

  4. Induction of labour in term premature rupture of membranes; oxytocin versus sublingual misoprostol; a randomised clinical trial.

    Science.gov (United States)

    Pouralil, Leila; Saghafi, Nafiseh; Eslami Hasan Abadi, Saeed; Tara, Fatemeh; Vatanchi, Atieh Mohamadzadeh; Motamedi, Elham

    2017-08-08

    Premature rupture of the membranes (PROM) occurs in about 8-10% of pregnancies and its most important complication is chorioamnionitis, so labour induction has an important role in this situation. This study was performed to compare oxytocin and sublingual Misoprostol for labour induction in PROM cases with term pregnancy. A total of 270 pregnant women who had spontaneous rupture of membrane and unripe cervix were enrolled. The first group underwent Oxytocin infusion according to low-dose standard protocol and the second group received 25 μg sublingual Misoprostol every 4 h. Time interval from induction to the beginning of active phase of labour was similar in both groups. Second stage of labour was significantly shorter in misoprostol group (p induction in PROM cases. Impact statement What is already known on this subject: PROM occurs in about 8-10% of pregnancies; about 60% of these cases are term pregnancies. Most experts recommend early induction of labour in term PROM cases with an eye towards avoiding increased morbidity and mortality. Oxytocin is the most frequently used agent that is administered intravenously for the purpose of labour induction. Misoprostol is an alternative to oxytocin and is simpler to use, as it is administered via the oral, buccal, sublingual, rectal and vaginal routes rather than intravenously. What do the results of this study add: Time interval from induction to the beginning of active phase of labour was similar in both groups. Second stage of labour was significantly shorter in the misoprostol group. Although, some maternal side-effects were significantly higher in misoprostol group, the 5 minute Apgar score was significantly better in this group. What are the implications of these finding for clinical practice and/or further research: Sublingual misoprostol for induction of labour in PROM cases is more effective than oxytocin and its neonatal outcomes are better. Due to its easy prescription and better labour outcomes

  5. Effectiveness of sublingual nitroglycerin before puncture compared with conventional intra-arterial nitroglycerin in transradial procedures: a randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Turan, Burak, E-mail: drburakturan@gmail.com; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

    2015-10-15

    Aim: Sublingual (SL) nitroglycerin administered before radial artery puncture can improve cannulation success and decrease the incidence of radial artery spasm (RAS) compared with intra-arterial (IA) nitroglycerin in transradial procedures. Methods: Patients undergoing diagnostic transradial angiography were randomized to IA (200 mcg) or SL (400 mcg) nitroglycerin. Primary endpoints were puncture time and puncture attempts. Secondary endpoint was the incidence of RAS. Results: Total of 101 participants (mean age 60 ± 11 years, 53% male) were randomized (51 in IA and 50 in SL groups). Puncture time (50 [36–75] vs 50 [35–90] sec), puncture attempts (1.18 ± 0.48 vs 1.20 ± 0.49), multiple punctures (13.7 vs 16.0%) and RAS (19.6 vs 24.0%) were not statistically different between IA vs SL groups respectively. A composite endpoint of all adverse events related to transradial angiography (multiple punctures, RAS, access site crossover, hypotension/bradycardia associated with nitroglycerin and radial artery occlusion) was very similar in IA vs SL groups (39 vs 40%, respectively). However puncture time was significantly longer with SL nitroglycerin in patients < 1.65 m height (47 [36–66] vs 63 [41–110] sec, p = 0.042). Multiple punctures seemed higher with SL nitroglycerin in patients with diabetes (0 vs 30%, p = 0.028) or in patients < 1.65 m height (7.4 vs 25%, p = 0.085). Likewise, RAS with SL nitroglycerin seemed more frequent in smokers compared to IA nitroglycerin (0 vs 27%, p = 0.089). Conclusions: SL nitroglycerin was not different from IA nitroglycerin in terms of efficiency and safety in overall study population. However it may be inferior to IA nitroglycerin in certain subgroups (shorter individuals, diabetics and smokers). - Highlights: • Improvement in radial artery puncture time and success with subcutaneous nitrate was reported. • Giving nitrate sublingually may have vasodilation along entire length of radial artery and may prevent RAS

  6. Sublingual immunization with adenovirus F protein-based vaccines stimulates protective immunity against botulinum neurotoxin A intoxication

    OpenAIRE

    Jun, SangMu; Clapp, Beata; Zlotkowska, Dagmara; Hoyt, Teri; Holderness, Kathryn; Maddaloni, Massimo; Pascual, David W.

    2011-01-01

    Sublingual (s.l.) vaccination is an efficient way to induce elevated levels of systemic and mucosal immune responses. To mediate mucosal uptake, ovalbumin (OVA) was genetically fused to adenovirus 2 fiber protein (OVA-Ad2F) to assess whether s.l. immunization was as effective as an alternative route of vaccination. Ad2F-delivered vaccines were efficiently taken up by dendritic cells and migrated mostly to submaxillary gland lymph nodes, which could readily stimulate OVA-specific CD4+ T cells....

  7. Clinical evaluation for sublingual immunotherapy with Dermatophagoides farinae drops in adult patients with allergic asthma.

    Science.gov (United States)

    Zhong, C; Yang, W; Li, Y; Zou, L; Deng, Z; Liu, M; Huang, X

    2017-10-14

    The efficacy and safety of sublingual immunotherapy (SLIT) in house dust mite-induced allergic asthma (AA) have yet to be firmly established, especially in adult patients. Our objective is to evaluate the efficacy of SLIT with Dermatophagoides farinae drops in adult patients with AA. One hundred and thirty-four adult patient data with house dust mite (HDM)-induced AA who had been treated for 2 years were collected. These patient data that we collected were divided into the SLIT group (n = 85) and control group (n = 49). All patients were treated with low to moderate dose of inhaled glucocorticoid and long-acting β2 agonists. Patients in the SLIT group were further treated with D. farinae drops. Clinical scores including the total asthma symptom score (TASS), total asthma medicine score (TAMS), asthma control test (ACT), and peak flow percentage (PEF%) were assessed before treatment and at yearly visits. The presence of adverse events (AEs) were recorded once a month. Before treatment, the PEF% in the SLIT group was significantly lower than that in the control group (p < 0.05). After 2 years, both treatments were effective in the clinical scores when compared with baseline values (all p < 0.001). Meanwhile, the SLIT group showed significantly lower TASS and TAMS (all p < 0.001) and higher ACT (p < 0.001) and PEF% (p < 0.05) when compared with the control group. No severe systemic AEs were reported. SLIT with D. farinae drops plus pharmacotherapy is more effective than routine drug treatment in adult patients with AA.

  8. Parietaria sublingual allergoid immunotherapy with a co-seasonal treatment schedule.

    Science.gov (United States)

    D'Anneo, R W; Arena, A; Gammeri, E; Bruno, M E; Falagiani, P; Riva, G; Leonardi, S; La Rosa, M

    2008-01-01

    Sublingual immunotherapy (SLIT) with monomeric allergoid, given according to the standard scheme, resulted effective and safe. However, the achievement of a clinical benefit requires a long time. We thus performed this study using an administration protocol starting in the co-seasonal period with a 3-day build-up phase and lasting only 6 months, in order to obtain the above benefit in a shorter time. The study, prospective, randomised and controlled versus drug therapy, was conducted on 65 rhinitic and/or asthmatic patients allergic to Parietaria with or without other sensitisations. Twenty-four were allocated to 1,000 AU/week, 21 to 3,000 AU/week and 21 to drug therapy. They were treated from April to September 2006. At baseline, 3 and 6 months a Visual Analogue Scale (VAS) was performed to assess the patients' well-being. Drug consumption was evaluated by means of monthly diary cards. Bronchial reactivity was investigated at baseline and 6 months by methacholine challenge test. There was a greater VAS improvement in both the SLIT groups than in the controls after 6 months (p<0.05). In patients taking 3,000 AU/week this was already evident after 3 months. There was a significant reduction in rescue medication consumption between 3 and 6 months (p<0.05) in all three groups. The bronchial reactivity was reduced only in the SLIT groups (p<0.001). No adverse events were observed. At 6 months the allergoid SLIT showed itself to be effective and safe. In addition the subjective clinical benefit was obtained in a more rapid period, i.e. 3 instead of 6 months, when a higher maintenance dose was administered.

  9. The efficacy of sublingual immunotherapy with Dermatophagoides farinae vaccine in a murine atopic dermatitis model.

    Science.gov (United States)

    Liu, L; Guo, D; Liang, Q; Ding, S; Wu, B; Zhang, L; Li, Q

    2015-04-01

    Sublingual immunotherapy (SLIT) is a potential treatment for house dust mite-induced atopic dermatitis (AD). However, the mechanisms of action are not clear. To establish a mouse model of AD in order to study the effect and mechanisms of SLIT. Mice were sensitized and subsequently challenged by repeated cutaneous application of Der f allergen extract. Sensitized mice were SLIT-treated with a Der f vaccine and analyzed for AD symptoms, histopathological and immunological parameters. This experiment was carried in the Laboratory Animal Center, Shanghai University of TCM. Repeated application of Der f extract caused rapid increase in dermatitis scores. Clinical findings (scratching behaviour, dermatitis and oedema) and histological symptoms (inflammatory cell infiltration) in this model were very similar to those in human AD. Serum total and Der f-specific IgE and IgG levels, and the expression level of T helper (Th)2 cytokine IL-5, IL-13; and Th1 cytokine IL-12 and IFN-γ were elevated compared with the control mice. SLIT treatment of sensitized mice markedly reduced the clinical and histopathological symptoms and decreased both Th1 and Th2 cytokine levels. The mouse model induced by Der f allergen extract reflected the typical hallmarks of human AD. In the Der f allergens-sensitized mice, SLIT treatment with Der f vaccine was shown to significantly inhibit AD symptoms through correction of Th2 and Th1 cytokine predominance. Our study suggested that SLIT could be considered as an attractive treatment for patients with extrinsic AD. © 2014 John Wiley & Sons Ltd.

  10. 3D printing of rat salivary glands: The submandibular-sublingual complex.

    Science.gov (United States)

    Cecchini, M P; Parnigotto, M; Merigo, F; Marzola, P; Daducci, A; Tambalo, S; Boschi, F; Colombo, L; Sbarbati, A

    2014-06-01

    The morphology and the functionality of the murid glandular complex, composed of the submandibular and sublingual salivary glands (SSC), were the object of several studies conducted mainly using magnetic resonance imaging (MRI). Using a 4.7 T scanner and a manganese-based contrast agent, we improved the signal-to-noise ratio of the SSC relating to the surrounding anatomical structures allowing to obtain high-contrast 3D images of the SSC. In the last few years, the large development in resin melting techniques opened the way for printing 3D objects starting from a 3D stack of images. Here, we demonstrate the feasibility of the 3D printing technique of soft tissues such as the SSC in the rat with the aim to improve the visualization of the organs. This approach is useful to preserve the real in vivo morphology of the SCC in living animals avoiding the anatomical shape changes due to the lack of relationships with the surrounding organs in case of extraction. It is also harmless, repeatable and can be applied to explore volumetric changes occurring during body growth, excretory duct obstruction, tumorigenesis and regeneration processes. 3D printing allows to obtain a solid object with the same shape of the organ of interest, which can be observed, freely rotated and manipulated. To increase the visibility of the details, it is possible to print the organs with a selected zoom factor, useful as in case of tiny organs in small mammalia. An immediate application of this technique is represented by educational classes. © 2013 Blackwell Verlag GmbH.

  11. Safety of ragweed sublingual allergy immunotherapy tablets in adults with allergic rhinoconjunctivitis.

    Science.gov (United States)

    Nayak, Anjuli S; Atiee, George J; Dige, Ea; Maloney, Jennifer; Nolte, Hendrik

    2012-01-01

    A sublingually administered allergy immunotherapy tablet (AIT) is under development to treat ragweed (Ambrosia artemisiifolia)-induced allergic rhinoconjunctivitis (ARC). This study investigates the optimal tolerable dose of once daily ragweed pollen AIT.Subjects 18-50 years old with ragweed-induced ARC were enrolled at two U.S. centers in a double-blind, placebo-controlled,dose-escalation study outside ragweed season. Groups (12 subjects each) were to be randomized 3:1 to 28 days of active treatment (groups assigned in sequence to 3, 6, 12, 24, 50, or 100 units of Ambrosia artemislifolia major allergen 1 [Amb a 1 U],without dose buildup at any level) or matching placebo. Recruitment to 50 Amb a 1-U was discontinued because of adverse events (AEs) after four AIT subjects were enrolled; 100 Amb a 1-U was not initiated. Fifty-three subjects were randomized (AIT,n = 40; placebo, n = 13); four discontinued, all because of AEs (AIT, n = 3; placebo, n = 1). Treatment-related AEs (TRAEs) were more frequent with AIT (73%) than placebo (31%), increasing with dose level. AIT TRAEs were mostly mild (94%) or moderate(5%). No serious TRAEs or anaphylactic shock occurred. The most common TRAEs with AIT were localized pruritus, nasal irritation, and throat irritation. Median onset for common AIT application site reactions was 24 ≤ hours after first treatment (median duration, 15-50 minutes). AIT increased immunoglobulin (Ig) significantly more than placebo (ragweed-specific IgE [6, 12, and 24 Amb a 1-U]; IgG4 [all doses]; p < 0.05). Three subjects in dose groups ≥ 24 Amb a 1-U experienced symptoms suggestive of systemic reaction. Of tested doses, ragweed AIT 24

  12. Influence of food on pharmacokinetics of zolpidem from fast dissolving sublingual zolpidem tartrate tablets.

    Science.gov (United States)

    Greenblatt, David J; Harmatz, Jerold S; Singh, Nikhilesh N; Roth, Thomas; Harris, Stephen C; Kapil, Ram P

    2013-11-01

    Ingesting food can impact the pharmacokinetics of sedative-hypnotic drugs. A buffered zolpidem sublingual tablet (ZST) recently became available for the treatment of middle-of-the-night awakening. In this randomized, open-label, single-site study, the pharmacokinetic profile of ZST was evaluated when administered while fasting and following a standard high-fat meal (fed state). Healthy adults aged 18-64 years received a single morning dose of 3.5 mg ZST in the fed or fasting state. From 20 min to 3 h post-dose, zolpidem plasma levels were lower in the fed state compared to the fasting state. After 4 h post-dose (corresponding to "morning wake time"), higher zolpidem plasma levels were evident in the fed state. Area under the concentration-time curve (AUC) values for the 0-8 h interval were 160 ng/mL h in the fed state and 203 ng/mL h in the fasting state (P fasting states, Cmax was 32.0 ng/mL versus 57.3 ng/mL (P < .001), respectively, and Tmax was 3.0 h versus 0.92 h (P < .001), respectively. Together these data suggest that administration of ZST in the fed state is not optimal for maximizing the likelihood of therapeutic benefit and minimizing the probability of residual sedation. © 2013, The American College of Clinical Pharmacology.

  13. Development of a Report Card for Identifying Local Sublingual Immunotherapy Events in Clinical Trials.

    Science.gov (United States)

    Norquist, Josephine; Flood, Emuella; Tanzosh, Tiffany; Li, Haojie; Iskold, Beata; Ganser, Thelma Rose; Marson-Smith, Helen

    2017-08-01

    The sublingual immunotherapy (SLIT) Report Card was developed to capture patient-reported local reactions from the administration of SLIT, based on the World Allergy Organization side-effect grading system. The objective was to evaluate understandability, usability, and translatability of the paper and electronic versions of the SLIT Report Card. Adults (aged 18+ years), adolescents (aged 12-17 years), and parents/caregivers and their children (aged 5-11 years) participated in two rounds of interviews, testing the paper version in Round 1, and both the paper and electronic versions in Round 2. Interviews assessed comprehension and usability by subjects. Translatability identified potential issues related to translation or cultural relevance. Ten adults, ten adolescents, and ten parent/child dyads were interviewed. In general, subjects demonstrated a clear understanding of the instrument's content. However, some subjects were uncertain of or suggested clarifying the meaning of certain terms, including tablet, ulcer, taste alteration, uvula, nausea, and itching in the ear. The translatability assessment also identified uvula and nausea as potentially problematic for translation. Subjects could use the electronic device and found navigation 'easy', with only a few minor suggestions made to improve usability. Some wording and formatting changes were made based on subjects' feedback and the translatability assessment. The SLIT Report Card was refined following best practices for instrument development, including cognitive interviewing, usability, and translatability assessment. The refined SLIT Report Card is appropriate for comprehensively and systematically collecting SLIT-related local reactions directly from subjects in a clinical trial setting, taking into account the World Allergy Organization grading system.

  14. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Ghasem Soltani

    2015-10-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  15. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Ghasem Soltani

    2015-09-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  16. Sublingual immunotherapy: a double-blind, placebo-controlled trial with Parietaria judaica extract standardized in mass units in patients with rhinoconjunctivitis, asthma, or both.

    Science.gov (United States)

    Purello-D'Ambrosio, F; Gangemi, S; Isola, S; La Motta, N; Puccinelli, P; Parmiani, S; Savi, E; Ricciardi, L

    1999-09-01

    New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy. We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica-induced respiratory allergy. A double-blind, placebo-controlled design was followed. Thirty patients with P. judaica rhinoconjunctivitis, mild asthma, or both were randomly chosen for sublingual immunotherapy (14 patients) or placebo treatment (16 patients). The patients underwent preseasonal rush induction treatment followed by coseasonal maintenance treatment during the Parietaria pollen season. Symptom and drug scores, as well as specific IgE and specific IgG4, were recorded. Significantly lower symptom and drug scores were found (P=0.04), especially during the Parietaria pollination period, in the immunotherapy group. No significant difference in specific IgE and specific IgG4 was detected between the active and placebo groups; a statistically significant increase of specific IgE was detected in both groups (P=0.05). No patient undergoing active sublingual immunotherapy reported local or systemic side-effects. Our data suggest that sublingual immunotherapy is both clinically effective and safe in treating patients with Parietaria-induced rhinoconjunctivitis and mild asthma.

  17. Study Design of the Microcirculatory Shock Occurrence in Acutely Ill Patients (microSOAP): an International Multicenter Observational Study of Sublingual Microcirculatory Alterations in Intensive Care Patients

    Science.gov (United States)

    Vellinga, Namkje A. R.; Boerma, E. Christiaan; Koopmans, Matty; Donati, Abele; Dubin, Arnaldo; Shapiro, Nathan I.; Pearse, Rupert M.; Bakker, Jan; Ince, Can

    2012-01-01

    Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Methods. 36 ICU's worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill. PMID:22666566

  18. Study Design of the Microcirculatory Shock Occurrence in Acutely Ill Patients (microSOAP: an International Multicenter Observational Study of Sublingual Microcirculatory Alterations in Intensive Care Patients

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    Namkje A. R. Vellinga

    2012-01-01

    Full Text Available Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP. Methods. 36 ICU’s worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill.

  19. Efficacy of a preservative-free formulation of fixed-combination bimatoprost and timolol (Ganfort PF in treatment-naïve patients vs previously treated patients

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    Cordeiro MF

    2015-08-01

    Full Text Available M Francesca Cordeiro,1 Ivan Goldberg,2 Rhett Schiffman,3 Paula Bernstein,3 Marina Bejanian31Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK; 2Discipline of Ophthalmology, University of Sydney, Sydney, NSW, Australia; 3Allergan, Inc., Irvine, CA, USAPurpose: To evaluate, using subgroup analysis, the effect of treatment status on the intraocular pressure (IOP-lowering efficacy of a preservative-free formulation of fixed-combination bimatoprost 0.03%/timolol 0.5% (FCBT PF.Methods: A primary, multicenter, randomized, double-masked, 12-week study compared the efficacy and safety of FCBT PF with preserved FCBT (Ganfort® in 561 patients diagnosed with glaucoma or ocular hypertension. For this analysis, eligible patients were treatment-naïve or had inadequate IOP lowering and underwent a washout of previous treatment. IOP (8 am, 10 am, and 4 pm was measured at baseline and weeks 2, 6, and 12. Subgroup analysis of the FCBT PF arm assessed changes in average eye IOP from baseline in treatment-naïve vs previously treated patients. To evaluate the effect of treatment status at baseline (treatment-naïve vs previously treated on IOP reduction in the FCBT PF treatment group, an analysis of covariance model was used with treatment status and investigator as fixed effects, and baseline average eye IOP, age, glaucoma diagnosis, and baseline average eye corneal thickness as covariates. P-values and the 95% confidence intervals were determined using the model.Results: In the FCBT PF arm, IOP mean changes from baseline ranged from -8.7 mmHg to -9.8 mmHg in treatment-naïve patients (N=50, compared with -7.3 mmHg to -8.5 mmHg in previously treated patients (N=228. Baseline IOP, age, glaucoma diagnosis, and corneal thickness significantly affected IOP reduction in the FCBT PF group. Adjusting for these covariates, FCBT PF had a greater IOP-lowering effect (0.8–1.7 mmHg in treatment-naïve patients than previously treated patients

  20. Network meta-analysis shows commercialized subcutaneous and sublingual grass products have comparable efficacy.

    Science.gov (United States)

    Nelson, Harold; Cartier, Shannon; Allen-Ramey, Felicia; Lawton, Simon; Calderon, Moises A

    2015-01-01

    Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have been shown to effectively treat grass pollen allergies, although direct comparisons are sparse. To estimate the relative efficacy of SLIT tablets compared with SCIT and SLIT drops in commercially available products though network meta-analysis. A literature search of MEDLINE, Embase, and Cochrane Library publications. Randomized, double-blind clinical trials of SCIT, SLIT drops, and SLIT tablets for grass pollen were included. Bayesian network meta-analyses estimated the standardized mean difference (SMD) across 3 immunotherapy modalities on allergic rhinoconjunctivitis symptom and medication score data from publications or received from authors. Both fixed and random effects models were investigated. Thirty-seven studies were included in meta-analyses for symptom scores and 31 studies for medication scores. In the random effects model, SCIT and SLIT tablets were significantly different from placebo for symptom scores: SMDs (95% CI) of -0.32 (-0.45 to -0.18) and -0.32 (-0.41 to -0.23), respectively. No significant difference was identified for SLIT drops compared with placebo (SMD, -0.17; -0.37 to 0.04). For medication scores, significant differences compared with placebo were observed for SCIT (SMD, -0.33; 95% CI, -0.52 to -0.13), SLIT tablets (SMD, -0.23; 95% CI, -0.29 to -0.17), and SLIT drops (SMD, -0.44; 95% CI, -0.83 to -0.06). Network meta-analysis revealed no significant differences in SMDs (95% credible interval) for symptom scores (0.0145 [-0.19 to 0.23]) or medication scores (0.133 [-0.31 to 0.57]) between SLIT tablets and SCIT, or for symptom scores (-0.175 [-0.37 to 0.02]) and medication scores (0.188 [-0.18 to 0.56]) between SLIT tablets and SLIT drops. The comparisons for grass pollen immunotherapy products commercialized in at least 1 country indicate comparable reductions in allergic rhinoconjunctivitis symptoms and supplemental medication use for SLIT tablets

  1. Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: Pooled analyses.

    Science.gov (United States)

    Durham, Stephen R; Creticos, Peter S; Nelson, Harold S; Li, Ziliang; Kaur, Amarjot; Meltzer, Eli O; Nolte, Hendrik

    2016-10-01

    Data comparing the treatment effect of allergy immunotherapy and pharmacotherapy are lacking. We sought to indirectly compare the treatment effect of sublingual immunotherapy (SLIT)-tablets with pharmacotherapy for seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). Pooled data from randomized, double-blind, placebo-controlled trials for the clinical development programs of selected allergic rhinitis treatments were evaluated. Total nasal symptom scores (TNSSs) relative to placebo were compared. Subjects scored symptoms daily during entire pollen seasons in 6 timothy grass SLIT-tablet trials (n = 3094) and 2 ragweed SLIT-tablet trials (n = 658) and during the last 8 weeks of treatment in 2 house dust mite (HDM) SLIT-tablet trials (n = 1768). Subjects scored symptoms daily in 7 montelukast (10 mg, n = 6799), 9 desloratadine (5 mg, n = 4455), and 8 mometasone furoate nasal spray (MFNS; 200 μg daily, n = 2140) SAR or PAR trials. SLIT-tablet trials allowed rescue medication use, whereas most pharmacotherapy trials did not. A fixed-effect meta-analysis method estimated differences in on-treatment average TNSSs. In grass and ragweed SLIT-tablet trials, overall improvement in TNSSs relative to placebo was 16.3% and 17.1%, respectively. In HDM SLIT-tablet trials, TNSS overall improvement relative to placebo was 16.1%. In the montelukast, desloratadine, and MFNS trials, TNSS overall improvement relative to placebo was 5.4%, 8.5%, and 22.2%, respectively, for SAR trials, and 3.7%, 4.8%, and 11.2%, respectively, for PAR trials. Although comparisons were limited by study design heterogeneity and use of rescue medications in SLIT-tablet trials, effects on nasal symptoms with timothy grass and ragweed SLIT-tablets were nearly as great as with MFNS and numerically greater than with montelukast and desloratadine for SAR. HDM SLIT-tablet effects were numerically greater than all pharmacotherapies for PAR. SLIT-tablets offer the additional

  2. Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site.

    Science.gov (United States)

    Messenger, Kristen M; Davis, Jennifer L; LaFevers, Douglas H; Barlow, Beth M; Posner, Lysa P

    2011-07-01

    To describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration. Randomized crossover experiment; prospective study. Eleven healthy adult horses between 6 and 20 years of age and weighing 487-592 kg. In the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg(-1)) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg(-1) SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility. Following IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg(-1) minute(-1) and volume of distribution at steady-state was 3.16 ± 0.65 L kg(-1). Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported. Buprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity

  3. Sublingual versus subcutaneous immunotherapy: patient adherence at a large German allergy center

    Directory of Open Access Journals (Sweden)

    Lemberg M

    2017-01-01

    Full Text Available Marie-Luise Lemberg,1 Till Berk,2 Kija Shah-Hosseini,1 Elena-Manja Kasche,1,3 Ralph Mösges1 1Faculty of Medicine, Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany; 2Department of Trauma Surgery, University Hospital Zurich, Zurich, Switzerland; 3Center for Dermatology, Specific Allergology and Environmental Medicine, Hamburg, Germany Background: Many placebo-controlled studies have demonstrated that allergen immunotherapy (AIT is an effective therapy for treating allergies. Both commonly used routes, subcutaneous (SCIT and sublingual immunotherapy (SLIT, require high patient adherence to be successful. In the literature, numbers describing adherence vary widely; this investigation compares these two routes of therapy directly.Methods: All data were retrieved from the patient data management system of a center for dermatology, specific allergology, and environmental medicine in Germany. All 330 patients (aged 13–89 years included in this study had commenced AIT between 2003 and 2011, thus allowing a full 3-year AIT cycle to be considered for each investigated patient.Results: In this specific center, SCIT was prescribed to 62.7% and SLIT to 37.3% of all included patients. The total dropout rate of the whole patient cohort was 34.8%. Overall, SLIT patients showed a higher dropout rate (39.0% than did SCIT patients (32.4%; however, the difference between these groups was not significant. Also, no significant difference between the overall dropout rates for men and for women was observed. A Kaplan–Meier curve of the patient collective showed a remarkably high dropout rate for the first year of therapy.Conclusion: The analysis presented in this single-center study shows that most patients who discontinue AIT do so during the first year of therapy. Patients seem likely to finish the 3-year therapy cycle if they manage to adhere to treatment throughout the first year. Strategies for preventing

  4. Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: study design and recruitment

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    de Jongste Johan C

    2008-10-01

    Full Text Available Abstract Background For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized double-blind placebo-controlled study was designed to establish the efficacy of sublingual immunotherapy with house dust mite allergen compared to placebo treatment in 6 to18-year-old children with allergic rhinitis and a proven house dust mite allergy in primary care. Described here are the methodology, recruitment phases, and main characteristics of the recruited children. Methods Recruitment took place in September to December of 2005 and 2006. General practitioners (in south-west Netherlands selected children who had ever been diagnosed with allergic rhinitis. Children and parents could respond to a postal invitation. Children who responded positively were screened by telephone using a nasal symptom score. After this screening, an inclusion visit took place during which a blood sample was taken for the RAST test. Results A total of 226 general practitioners invited almost 6000 children: of these, 51% was male and 40% Conclusion Our study was designed in accordance with recent recommendations for research on establishing the efficacy of sublingual immunotherapy; 98% of the target sample size was achieved. This study is expected to provide useful information on sublingual immunotherapy with house dust mite allergen in primary care. The results on efficacy and safety are expected to be available by 2010. Trial registration the trial is registered as ISRCTN91141483 (Dutch Trial Register

  5. Intraoperative temperature monitoring with zero heat flux technology (3M SpotOn sensor) in comparison with sublingual and nasopharyngeal temperature: An observational study.

    Science.gov (United States)

    Iden, Timo; Horn, Ernst-Peter; Bein, Berthold; Böhm, Ruwen; Beese, Janne; Höcker, Jan

    2015-06-01

    Perioperative hypothermia is common in patients undergoing general anaesthesia and is associated with important adverse events. The 'gold standard' for monitoring body core temperature - the pulmonary artery catheter - is invasive and unsuitable for most patients. For routine clinical practice, other sites and methods of temperature monitoring are commonly used. The aim of this study was to evaluate a new temperature sensor (3M SpotOn) using the 'zero heat flux' method attached to the forehead, and compare it to sublingual and nasopharyngeal sensors in terms of correlation, accuracy and precision. An observational study. University Medical Center Schleswig Holstein, Campus Kiel, Germany from October 2013 to January 2014. One hundred and twenty patients scheduled for elective gynaecological or trauma surgery undergoing general anaesthesia were enrolled into this study. Data of 83 patients were finally analysed. Patients with unexpected blood loss, haemodynamic instability determined by the need for continuous norepinephrine infusion and/or need for postoperative ventilation were excluded from this study. Temperature monitoring was established after induction of anaesthesia with sublingual and nasopharyngeal probes, and the SpotOn sensor. Body temperature was measured 15, 45 and 75 min after induction of anaesthesia from sublingual and nasopharyngeal probes and the 3M SpotOn sensor at precisely the same moment. Analysis of 83 data sets revealed that 3M SpotOn temperatures were almost identical with nasopharyngeal temperatures (mean difference 0.07 °C; P = 0.1424) and slightly lower than sublingual temperatures by 0.35 °C (P sensor provides a good measurement of body temperature in comparison to the nasopharyngeal probe and an acceptable measurement in comparison with sublingual thermometry. It is adequate for clinical use. Clinicaltrials.gov identifier: NCT02031159.

  6. Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined from oral morphine rescue doses in the treatment of breakthrough cancer pain.

    Science.gov (United States)

    Shimoyama, Naohito; Gomyo, Ikuo; Teramoto, Osamu; Kojima, Keisuke; Higuchi, Hitomi; Yukitoshi, Nobuyuki; Ohta, Eri; Shimoyama, Megumi

    2015-02-01

    A randomized, crossover, double-blinded placebo-controlled and non-blinded active drug-controlled, comparative clinical trial was conducted to evaluate the efficacy and safety of sublingual fentanyl tablet. Subjects were patients treated with strong opioids at fixed intervals for chronic cancer pain and with oral morphine as rescue medication for breakthrough pain. Sublingual fentanyl was administered at doses that were 1/25th (high dose) and 1/50th (low dose) of the dose of rescue morphine and was compared with placebo and oral morphine. The primary endpoint was pain intensity difference at 30 min after administration. (Clinical Trials Government; NCT00684632). Fifty-one patients were enrolled in the investigation. Their mean pain intensity in visual analog scale before rescue medication prior to the investigation was 60.96 (16.44, standard deviation) mm. Compared with placebo, the low and high doses of sublingual fentanyl showed significant analgesic effects (least squares mean difference, 4.54 and 8.49 mm; P = 0.014, P pain and with oral morphine at doses up to 20 mg as rescue medication were investigated. The doses of sublingual fentanyl to treat breakthrough pain were determined from rescue morphine doses by use of conversion ratios. In these patients, administration of sublingual fentanyl at doses determined by a conversion ratio of 1/50 was effective and safe. Further studies are needed to validate the use of this conversion method. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Baixa dose de misoprostol sublingual (12,5 µg para indução do parto Low dose of sublingual misoprostol (12.5 µg for labor induction

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    Daniele Sofia de Moraes Barros Gattás

    2012-04-01

    Full Text Available OBJETIVO: Descrever os resultados maternos e perinatais utilizando 12,5 µg de misoprostol sublingual para indução do parto em gestantes com feto vivo a termo. MÉTODOS: Realizou-se um estudo multicêntrico, tipo ensaio clínico, aberto e não randomizado, no período de julho a dezembro de 2009. Foram incluídas 30 gestantes com indicação de indução do parto, a termo, feto vivo, escore de Bishop menor ou igual a seis, apresentação cefálica, peso fetal estimado menor que 4.000 g e índice de líquido amniótico maior que cinco. Foram excluídas mulheres com cicatriz uterina, alteração da vitalidade fetal, anomalias congênitas, gestação múltipla, restrição de crescimento intrauterino, hemorragia genital e contraindicações ao parto vaginal. O comprimido de misoprostol sublingual 12,5 µg foi administrado a cada seis horas, até o início do trabalho de parto, máximo de oito doses. RESULTADOS: O trabalho de parto foi induzido satisfatoriamente em 90% das gestantes. As médias dos intervalos entre a primeira dose e o início das contrações uterinas e o parto foram de 14,3±11,7 horas e 25,4±13 horas, respectivamente. A frequência de parto vaginal foi de 60%. A taquissistolia ocorreu em duas gestantes, sendo revertida em ambos os casos sem necessitar de cesariana. A eliminação de mecônio foi observada em quatro pacientes e o escore de Apgar foi menor que sete no quinto minuto em um recém-nascido. CONCLUSÃO: Os desfechos maternos e perinatais foram favoráveis depois da indução do parto com misoprostol sublingual na dose de 12,5 µg a cada seis horas. No entanto, são necessários ensaios clínicos controlados comparando esse esquema posológico com outras doses e vias de administraçãoPURPOSE: To describe the maternal and perinatal outcomes after the use of 12.5 µg of sublingual misoprostol for labor induction in women with term pregnancy and a live fetus. METHODS: We conducted a multicenter, open and non

  8. Assessment of strategy formulation

    DEFF Research Database (Denmark)

    Acur, Nuran; Englyst, Linda

    2006-01-01

    Purpose – Today, industrial firms need to cope with competitive challenges related to innovation, dynamic responses, knowledge sharing, etc. by means of effective and dynamic strategy formulation. In light of these challenges, the purpose of the paper is to present and evaluate an assessment tool...... for strategy formulation processes that ensures high quality in process and outcome. Design/methodology/approach – A literature review was conducted to identify success criteria for strategy formulation processes. Then, a simple questionnaire and assessment tool was developed and used to test the validity...... of the success criteria through face-to-face interviews with 46 managers, workshops involving 40 managers, and two in-depth case studies. The success criteria have been slightly modified due to the empirical results, to yield the assessment tool. Findings – The resulting assessment tool integrates three generic...

  9. The role of barrier function of mucous membranes in allergic diseases and sublingual allergen-specific immunotherapy

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    Oksana M. Kurbacheva

    2017-01-01

    Full Text Available Currently one of the factors of allergy predisposition is the increase in barrier permeability of the mucous membranes of the respiratory system and the gastrointestinal tract (GIT. It defines the probability of an emergence of an allergic response. To understand the mechanisms of the interaction of the mucous membranes of different systems that explain their common function is undoubtedly necessary for discussion of this problem. The features of microbiome influence and the changes of the microbiome state during the formation of the immune response to the contact with allergens are of particular interest. The structure of the epithelial barrier of the airwaysand GIT, and mechanisms of allergen transport through barrier systems with the subsequent interaction with the cells (? associated with barrier fabrics have been considered. The possible role of the barrier function of mucous membranes in conducting sublingual allergen-specific immunotherapy (SLIT is discussed. 

  10. Safety of sublingual immunotherapy Timothy grass tablet in subjects with allergic rhinitis with or without conjunctivitis and history of asthma

    DEFF Research Database (Denmark)

    Maloney, J; Durham, S; Skoner, D

    2015-01-01

    BACKGROUND: Patients with asthma may be more susceptible to adverse events (AEs) with sublingual immunotherapy tablet (SLIT-tablet) treatment, such as severe systemic reactions and asthma-related events. Using data from eight trials of grass SLIT-tablet in subjects with allergic rhinitis with...... with uncontrolled and severe asthma were excluded from the trials. Frequencies for treatment-emergent AEs (TEAEs), local allergic swelling (mouth or throat), systemic allergic reactions, and asthma-related treatment-related AEs (TRAEs) were calculated. RESULTS: Among adults (n = 3314) and children (n = 881), 24......% and 31%, respectively, had reported asthma. No serious local allergic swellings or serious systemic allergic reactions occurred in subjects with asthma treated with SLIT-tablet. There was no evidence of increased TEAEs, systemic allergic reactions, or severe local allergic swellings in adults or children...

  11. Sublingual misoprostol versus standard surgical care for treatment of incomplete abortion in five sub-Saharan African countries

    Directory of Open Access Journals (Sweden)

    Shochet Tara

    2012-11-01

    Full Text Available Abstract Background In low-resource settings, where abortion is highly restricted and self-induced abortions are common, access to post-abortion care (PAC services, especially treatment of incomplete terminations, is a priority. Standard post-abortion care has involved surgical intervention but can be hard to access in these areas. Misoprostol provides an alternative to surgical intervention that could increase access to abortion care. We sought to gather additional evidence regarding the efficacy of 400 mcg of sublingual misoprostol vs. standard surgical care for treatment of incomplete abortion in the environments where need for economical non-surgical treatments may be most useful. Methods A total of 860 women received either sublingual misoprostol or standard surgical care for treatment of incomplete abortion in a multi-site randomized trial. Women with confirmed incomplete abortion, defined as past or present history of vaginal bleeding during pregnancy and an open cervical os, were eligible to participate. Participants returned for follow-up one week later to confirm clinical status. If abortion was incomplete at that time, women were offered an additional follow-up visit or immediate surgical evacuation. Results Both misoprostol and surgical evacuation are highly effective treatments for incomplete abortion (misoprostol: 94.4%, surgical: 100.0%. Misoprostol treatment resulted in a somewhat lower chance of success than standard surgical practice (RR = 0.90; 95% CI: 0.89-0.92. Both tolerability of side effects and women’s satisfaction were similar in the two study arms. Conclusion Misoprostol, much easier to provide than surgery in low-resource environments, can be used safely, successfully, and satisfactorily for treatment of incomplete abortion. Focus should shift to program implementation, including task-shifting the provision of post-abortion care to mid- and low- level providers, training and assurance of drug availability. Trial

  12. Could Sublingual Immunotherapy Affect Oral Health in Children with Asthma and/or Allergic Rhinitis Sensitized to House Dust Mite?

    Science.gov (United States)

    Kiykim, Ayca; Mumcu, Gonca; Ogulur, Ismail; Karakoc-Aydiner, Elif; Direskeneli, Haner; Baris, Safa; Cagan, Hasret; Ozen, Ahmet

    2017-01-01

    Sublingual immunotherapy (SLIT) has been successfully employed in IgE-mediated respiratory allergies. However, it is not known whether the modulation of immune responses in the sublingual area during SLIT has any deleterious effect on oral health. We sought to determine the oral health prospectively in children receiving SLIT for house dust mite allergy. Eighteen children with allergic asthma and/or rhinitis and 31 age-matched healthy controls (HC) were included in an open-labeled trial. Oral health was evaluated by scoring the decayed, missing, and filled teeth for primary (dmft) and permanent (DMFT) dentition, and the plaque and gingival indices. Moreover, cariogenic food intake and teeth-brushing habits were also noted at baseline and at 19 months. The mean age of the SLIT participants was 9.5 ± 3.1 years and that of the HC was 9.2 ± 3.7 years. The mean duration of SLIT was 19.13 ± 3.81 months. At baseline, the total dmft and DMFT indices were similar in the SLIT and HC groups (p > 0.05), which demonstrated poor hygiene overall. In the within-group comparisons at the examination at 19 months, the SLIT group had a lower number of carious primary teeth and a higher number of filled primary teeth compared to the count at baseline (p = 0.027 and p = 0.058, respectively). Our study showed no detrimental effect of SLIT on oral health during a period of 19 months of follow-up. Parents should be motivated to use dental health services to prevent new caries formation since our cohort had overall poor oral hygiene at the baseline. © 2017 S. Karger AG, Basel.

  13. Disparity between skin perfusion and sublingual microcirculatory alterations in severe sepsis and septic shock: a prospective observational study.

    Science.gov (United States)

    Boerma, E Christiaan; Kuiper, Michael A; Kingma, W Peter; Egbers, Peter H; Gerritsen, Rik T; Ince, Can

    2008-07-01

    Measurement of central-to-toe temperature difference has been advocated as an index of severity of shock and as a guide for circulatory therapy in critically ill patients. However, septic shock, in contrast to other forms of shock, is associated with a distributive malfunction resulting in a disparity between vascular compartments. Although this disparity has been established between systemic and microcirculatory parameters, it is unclear whether such disparity exists between skin perfusion and microcirculation. To test this hypothesis of disparity, we simultaneously measured parameters of the two vascular compartments, in the early phase of sepsis. Prospective observational study in patients with severe sepsis/septic shock in the first 6 h of ICU admission. Simultaneous measurements of central-to-toe temperature difference and sublingual microcirculatory orthogonal polarization spectral imaging, together with parameters of systemic hemodynamics. 22 bed mixed-ICU in a tertiary teaching hospital. 35 consecutive patients in a 12-month period. In 35 septic patients and a median APACHE II score of 20, no correlation between central-to-toe temperature gradient and microvascular flow index was observed (r (s) = -0.08, p =0.65). Also no significant correlation between temperature gradient/microvascular flow index and systemic hemodynamic parameters could be demonstrated. During the early phase of resuscitated severe sepsis and septic shock there appears to be no correlation between sublingual microcirculatory alterations and the central-to-toe temperature difference. This finding adds to the concept of a dispersive nature of blood flow under conditions of sepsis between microcirculatory and systemic hemodynamics.

  14. Disparity between skin perfusion and sublingual microcirculatory alterations in severe sepsis and septic shock: a prospective observational study

    Science.gov (United States)

    Kuiper, Michael A.; Kingma, W. Peter; Egbers, Peter H.; Gerritsen, Rik T.; Ince, Can

    2008-01-01

    Objective Measurement of central-to-toe temperature difference has been advocated as an index of severity of shock and as a guide for circulatory therapy in critically ill patients. However, septic shock, in contrast to other forms of shock, is associated with a distributive malfunction resulting in a disparity between vascular compartments. Although this disparity has been established between systemic and microcirculatory parameters, it is unclear whether such disparity exists between skin perfusion and microcirculation. To test this hypothesis of disparity, we simultaneously measured parameters of the two vascular compartments, in the early phase of sepsis. Design Prospective observational study in patients with severe sepsis/septic shock in the first 6 h of ICU admission. Simultaneous measurements of central-to-toe temperature difference and sublingual microcirculatory orthogonal polarization spectral imaging, together with parameters of systemic hemodynamics. Setting 22 bed mixed-ICU in a tertiary teaching hospital. Patients 35 consecutive patients in a 12-month period. Measurements and results In 35 septic patients and a median APACHE II score of 20, no correlation between central-to-toe temperature gradient and microvascular flow index was observed (rs = −0.08, p = 0.65). Also no significant correlation between temperature gradient/microvascular flow index and systemic hemodynamic parameters could be demonstrated. Conclusions During the early phase of resuscitated severe sepsis and septic shock there appears to be no correlation between sublingual microcirculatory alterations and the central-to-toe temperature difference. This finding adds to the concept of a dispersive nature of blood flow under conditions of sepsis between microcirculatory and systemic hemodynamics. PMID:18317733

  15. Sublingual misoprostol versus intravenous oxytocin in reducing bleeding during and after cesarean delivery: A randomized clinical trial.

    Science.gov (United States)

    Othman, Essam Rashad; Fayez, Margaret Fathy; El Aal, Diaa Eldeen Mohamed Abd; El-Dine Mohamed, Hazem Saad; Abbas, Ahmed Mohammed; Ali, Mohammed Khairy

    2016-12-01

    This study compares the efficacy of sublingual misoprostol versus intravenous oxytocin in reducing bleeding during and after cesarean delivery. A randomized clinical trial conducted on 120 pregnant women at term (37-40 weeks) gestation scheduled for elective cesarean delivery, who were assigned to either sublingual misoprostol 400 μg or intravenous infusion of 20 units of oxytocin after delivery of the neonate. The main outcome measures were blood loss at and 2 hours after cesarean delivery, change in hematocrit value, need for any additional oxytocic drugs, and drug-related side effects. The overall mean blood loss was significantly lower in the misoprostol group compared to the oxytocin group (490.75 ± 159.90 mL vs. 601.08 ± 299.49 mL; p = 0.025). However, changes in hematocrit level (pre- and postpartum) was comparable between both groups. There was a need for additional oxytocic therapy in 16.7% and 23.3% after use of misoprostol and oxytocin, respectively (p = 0.361). Incidence of side effects such as shivering and metallic taste were significantly higher in the misoprostol group compared to the oxytocin group (p effective than intravenous infusion of oxytocin in reducing blood loss during and after cesarean delivery. However, occurrence of temporary side effects such as shivering and metallic taste was more frequent with the use of misoprostol. Copyright © 2016. Published by Elsevier B.V.

  16. Design and formulation of mebeverine HCl semisolid formulations for intraorally administration.

    Science.gov (United States)

    Baloğlu, Esra; Karavana, Sinem Y; Hyusein, Ismail Yuksel; Köse, Timur

    2010-03-01

    Gel formulations of mebeverine hydrochloride (MbHCl) containing hydroxypropylmethylcellulose (HPMC), metolose (MTL), and poloxamer 407 (PLX) were prepared to be used in the treatment of different oral painful conditions. HPMC was used as a mucoadhesive gel base while MTL and PLX were used to prepare sol-gel thermosensitive gels. MTL and PLX formulations showed proper sol-gel transition temperature for intraoral application. Formulations were evaluated in terms of their viscosity, mechanical properties, mucoadhesivity, stability, and in vitro drug release. The formulation prepared with 2% of HPMC K100M provided the highest viscosity at room temperature. However, the viscosity of HPMC-PLX mixture showed a significant increase at body temperature. The greatest mucoadhesion was also noted in HPMC-PLX combinations. Texture profile analysis exhibited the differences of the adhesion, hardness, elasticity, cohesiveness, and compressibility of the formulations. The release profiles of MbHCl were obtained, and non-Fickian release was observed from all the formulations. The formulations were stored at different temperature and relative humidity. No significant changes were observed at the end of the 3 months. HPMC-PLX formulation of MbHCl was chosen for in vivo studies, and it remained longer than dye solution on the rabbit's intraoral mucosal tissue. It was found worthy of further clinical evaluation.

  17. Laboratory tests on the efficacy of VBC60035, a combined larvicidal formulation of Bacillus thuringiensis israelensis (strain AM65-52) and Bacillus sphaericus (strain 2362) against Aedes albopictus in simulated catch basins.

    Science.gov (United States)

    Eritja, Roger

    2013-09-01

    Catch basins are a common breeding site for mosquito larvae in urban areas. The arrival in Spain of the Asian tiger mosquito, Aedes albopictus, has turned catch basins into a challenging public health issue in some areas such as the Baix Llobregat region, where more than 135,000 units are treated per year in a large-scale application program. Although biorational larvicides are used, modern formulations providing longer efficacy periods could lead to manpower savings. Laboratory indoor trials are presented on the formulation VBC60035 (Vectomax FG), which is under registration in Spain. Indoor microcosms simulating real catch basins were treated and recolonized weekly using insectary-reared Ae. albopictus larvae. The trial took place over 2 seasons in the same water at dosages of 10, 50, and 577 kg/ha. At all 3 concentrations, the efficiency was close to 100% for up to 345 days posttreatment with 14.1% mean mortality in the control. Field factors including flushing, bacterial degradation, and toxic effluents in the drainage pools are discussed as limitations of indoor tests.

  18. Sublingual Misoprostol versus Intramuscular Oxytocin for Prevention of Postpartum Hemorrhage in Uganda: A Double-Blind Randomized Non-Inferiority Trial

    Science.gov (United States)

    Atukunda, Esther C.; Siedner, Mark J.; Obua, Celestino; Mugyenyi, Godfrey R.; Twagirumukiza, Marc; Agaba, Amon G.

    2014-01-01

    Background Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 µg, for prevention of PPH during active management of labor. Methods and Findings We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 µg of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss ≥500 ml within 24 h of delivery. Secondary outcomes included measured blood loss ≥1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, ppostpartum hemoglobin, change in hemoglobin, or use of additional uterotonics between study groups. Further research should focus on clarifying whether and in which sub-populations use of oxytocin would be preferred over sublingual misoprostol. Trial registration ClinicalTrials.gov NCT01866241 Please see later in the article for the Editors' Summary PMID:25369200

  19. Concomitant occurrence of primary hyperparathyroidism (PHPT) due to mediastinal parathyroid adenoma and sublingual thyroid gland: the role of parathyroid technetium-99m-MIBI scintigraphy.

    Science.gov (United States)

    Choukry, Sara; Benouhoud, Jaafar; Cherkaoui Salhi, Ghofrane; Taleb, Sara; Guensi, Amal; Choukry, Karim

    2017-11-01

    The concomitant appearance of a sublingual thyroid and primary hyperparathyroidism due to parathyroid mediastinal adenoma is not common. This co-occurrence can lead to a misdiagnosis by morphological imaging methods alone. This case emphasizes the role of 99mTc-MIBI scintigraphy in the detection of parathyroid ectopic adenoma in a patient with an ectopic thyroid gland. This more accurate location of parathyroid scintigraphy is of great benefit to the surgeon for surgical excision.

  20. A randomised comparison of oral desmopressin lyophilisate (MELT) and tablet formulations in children and adolescents with primary nocturnal enuresis

    DEFF Research Database (Denmark)

    Lottmann, H; Froeling, F; Alloussi, S

    2007-01-01

    AIMS: Desmopressin is a useful treatment for primary nocturnal enuresis (PNE), a common childhood condition that can persist into adolescence. This open-label, randomised, cross-over study evaluated the preference of children and adolescents with PNE for sublingual desmopressin oral lyophilisate...... for the MELT, and a statistically significant preference for desmopressin MELT in children aged 5-11 years. Desmopressin MELT had similar levels of efficacy and safety at lower dosing levels than the tablet, and therefore facilitates early initiation of PNE treatment in children aged 5-6 years. Udgivelsesdato.......88 +/- 1.94 bedwetting episodes/week; tablet: 1.90 +/- 1.85 episodes/week). Ease of use of both formulations was high. Compliance (> or = 80%) was 94.5% for MELT patients vs. 88.9% for the tablet (p = 0.059). No serious/severe adverse events were reported. CONCLUSIONS: There was an overall preference...

  1. Liposomal paclitaxel formulations.

    Science.gov (United States)

    Koudelka, Stěpán; Turánek, Jaroslav

    2012-11-10

    Over the past three decades, taxanes represent one of the most important new classes of drugs approved in oncology. Paclitaxel (PTX), the prototype of this class, is an anti-cancer drug approved for the treatment of breast and ovarian cancer. However, notwithstanding a suitable premedication, present-day chemotherapy employing a commercial preparation of PTX (Taxol®) is associated with serious side effects and hypersensitivity reactions. Liposomes represent advanced and versatile delivery systems for drugs. Generally, both in vivo mice tumor models and human clinical trials demonstrated that liposomal PTX formulations significantly increase a maximum tolerated dose (MTD) of PTX which outperform that for Taxol®. Liposomal PTX formulations are in various stages of clinical trials. LEP-ETU (NeoPharm) and EndoTAG®-1 (Medigene) have reached the phase II of the clinical trials; Lipusu® (Luye Pharma Group) has already been commercialized. Present achievements in the preparation of various liposomal formulations of PTX, the development of targeted liposomal PTX systems and the progress in clinical testing of liposomal PTX are discussed in this review summarizing about 30 years of liposomal PTX development. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Kunio Yoshizawa

    2016-01-01

    Full Text Available A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis.

  3. Down-regulation of Th2 immune responses by sublingual administration of poly (lactic-co-glycolic) acid (PLGA)-encapsulated allergen in BALB/c mice.

    Science.gov (United States)

    Salari, Farhad; Varasteh, Abdol-Reza; Vahedi, Fatemeh; Hashemi, Maryam; Sankian, Mojtaba

    2015-12-01

    The goal of this study was to investigate whether poly (lactic-co-glycolic) acid (PLGA) nanoparticles could enhance sublingual immunotherapy (SLIT) efficacy. BALB/c mice sensitized to rChe a 3 were treated sublingually either with soluble rChe a 3 (100μg/dose) or PLGA-encapsulated rChe a 3 (5, 25, or 50μg/dose). SLIT with PLGA-encapsulated rChe a 3 (equivalent to 25 and 50μg rChe a 3 per dose) led to significantly increased antigen-specific IgG2a, along with no effect on allergen-specific IgE and IgG1 antibody levels. In addition, interleukin 4 (IL-4) levels in restimulated splenocytes were significantly less, while interferon-γ (IFN-γ), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) levels, as well as Foxp3 expression, were significantly greater than in the control groups. Our findings suggest that PLGA nanoparticle-based vaccination may help rational development of sublingual immunotherapy through reduction of the needed allergen doses and also significantly enhanced systemic T regulatory (Treg) and T helper 1 (Th1) immune responses. Copyright © 2015. Published by Elsevier B.V.

  4. A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway.

    Directory of Open Access Journals (Sweden)

    Masahiro Fukasaka

    Full Text Available A lipopolysaccharide from Pantoea agglomerans (LPSpa has been applied to various fields for human use as a Toll-like receptor 4 ligand and its safety has been confirmed. Here, we showed for the first time the application of LPSpa as an effective mucosal adjuvant for activating vaccine-induced antigen specific immune responses. Mice sublingually immunized with influenza vaccine (HA split vaccine with LPSpa induced both HA-specific IgG (systemic and IgA (mucosal antibody responses, which led to a significant increase in survival rate against lethal influenza virus challenge compared with subcutaneous vaccination. After sublingual administration of ovalbumin with LPSpa, ovalbumin-specific mucosal IgA responses were induced at both mucosal surfaces close to the immunized site and at remote mucosal surfaces. Sublingual administration of LPSpa evoked local antigen-uptake by dendritic cells in cervical lymph nodes. LPSpa induced cytokine production and the maturation and proliferation of innate immune cells via Toll-like receptor 4 in dendritic cells. Collectively, these results suggest that LPSpa can be used as an effective mucosal adjuvant to stimulate and activate local innate immune cells to improve and enhance mucosal vaccine potency against various pathogens.

  5. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Erah

    hydrochloride using a combination of a hydrophobic carrier and a hydrophilic polymer, and two types of formulation techniques. Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer ..... be attributed to the dissolution of drug from the tablet surface.

  6. Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: study design and recruitment.

    Science.gov (United States)

    de Bot, Cindy M A; Moed, Heleen; Berger, Marjolein Y; Röder, Esther; de Groot, Hans; de Jongste, Johan C; van Wijk, Roy Gerth; van der Wouden, Johannes C

    2008-10-20

    For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized double-blind placebo-controlled study was designed to establish the efficacy of sublingual immunotherapy with house dust mite allergen compared to placebo treatment in 6 to 18-year-old children with allergic rhinitis and a proven house dust mite allergy in primary care. Described here are the methodology, recruitment phases, and main characteristics of the recruited children. Recruitment took place in September to December of 2005 and 2006. General practitioners (in south-west Netherlands) selected children who had ever been diagnosed with allergic rhinitis. Children and parents could respond to a postal invitation. Children who responded positively were screened by telephone using a nasal symptom score. After this screening, an inclusion visit took place during which a blood sample was taken for the RAST test. A total of 226 general practitioners invited almost 6000 children: of these, 51% was male and 40% <12 years of age. The target sample size was 256 children; 251 patients were finally included. The most frequent reasons given for not participating were: absence or mildness of symptoms, absence of house dust mite allergy, and being allergic to grass pollen or tree pollen only. Asthma symptoms were reported by 37% of the children. Of the enrolled children, 71% was sensitized to both house dust mite and grass pollen. Roughly similar proportions of children were diagnosed as being sensitized to one, two, three or four common inhalant allergens. Our study was designed in accordance with recent recommendations for research on establishing the efficacy of sublingual immunotherapy; 98% of the target sample size was achieved. This study is expected to provide useful information on

  7. Correction of vitamin D deficiency using sublingually administered vitamin D2 in a Crohn's disease patient with mal-absorption and a new ileostomy.

    Science.gov (United States)

    McCullough, Patrick; Heaney, Robert

    2017-10-01

    Vitamin D deficiency has been shown to be associated with many adverse health problems. Studies have shown that patients with Crohn's disease who have low vitamin D levels have a poorer quality of life than those with more adequate levels. It has also been shown that patients with mal-absorption problems have a difficult time achieving normal vitamin D levels in spite of aggressive supplementation, and that exposure to UVB radiation may be the most effective treatment option for these patients. We present a case in which 25-hydroxyvitamin D levels were normalized within 2 weeks in a severely vitamin D deficient patient with Crohn's disease with mal-absorption and a new ileostomy, utilizing sublingually administered vitamin D2. A 58 year-old white female was admitted with a new ileostomy following partial bowel resection due to complications from Crohn's disease. She was found to be severely vitamin D deficient at the time of admission, with a level of 6.1ng/ml on hospital day 3. Her treatment with vitamin D was delayed for a few days. She was initially treated with 5000 units of vitamin D3 orally twice a day for 3days (days 7-10). After discussion with the patient and obtaining her consent, vitamin D3 was stopped, and she was then treated with a total of 8 doses of 50,000 units of vitamin D2 administered sublingually. She was given the first 3 doses on alternating days (days 11, 13, 15), and then 5 more doses on consecutive days (days 17-21). The rise in her 25-hydroxyvitamin D level in response to treatment with sublingual vitamin D2 was significant. On day 10, after receiving 3days of orally administered vitamin D3, her level was 9.8ng/ml. One week later, after receiving 3 sublingual doses of vitamin D2, it rose to 20.3ng/ml. It was then measured on alternating days twice over the next 4days, and it rose to 45.5ng/ml, and then to 47.4ng/ml on the day of discharge to home. The major finding of this study is that sublingual administration of vitamin D2 appears to

  8. Inhalant allergy compounding the chronic vaginitis syndrome: characterization of sensitization patterns, comorbidities and responses to sublingual immunotherapy.

    Science.gov (United States)

    Theodoropoulos, Demetrios S; Stockdale, Colleen K; Duquette, Daniel R; Morris, Mary S

    2016-09-01

    To characterize sensitization patterns, diagnoses and comorbidities, and to assess the response of lower genital tract symptoms to sublingual immunotherapy for airborne allergens in a select population of patients with chronic vaginitis. Fifty-two patients referred for allergy evaluation over a 44 month period were studied. Charts were retrospectively reviewed to establish: (1) gynecological diagnoses, (2) allergic-immunological diagnoses, and (3) IgE-mediated sensitivity to airborne allergens on presentation. Patients were contacted at 9-50 months of treatment to assess response to sublingual immunotherapy based on a questionnaire addressing frequency and severity of symptoms and use of medication to control symptoms. Recurrent vulvovaginal candidiasis was identified in 34 (65 %); vulvar vestibulitis syndrome in 12 (23 %); and contact dermatitis in 10 (19 %) patients. Comorbidities included: non-reflux gastrointestinal complaints in 11 (21 %), gastroesophageal reflux in 5 (9 %), migraines in 9 (17 %), chronic non-migrainous headaches in 8 (17 %), and chronic sinusitis in 6 patients (11 %). Asthma was diagnosed in 8 patients (15 %). Oral allergy syndrome was present in 6 (11 %). Most frequent sensitivities were to: ragweed in 33 (63 %), molds in 26 (50 %), dust mites in 23 (44 %), and grass in 12 (23 %) patients. Mono-sensitization was demonstrated for ragweed in 7 (13 %), and for molds, dust mites and grass for 3 (5 %) patients each. Candida sensitization was identified in 15 patients with chronic vaginitis (28 %). Eleven patients with recurrent vulvovaginal diagnosis (32 %) showed Candida sensitization. Response to immunotherapy was generally favorable with pruritus/irritation being more responsive than visceral pain. In a Midwestern referral population, chronic vaginitis compounded by inhalant allergy showed: (1) high incidence rate of recurrent vulvo-vaginal candidiasis, (2) Candida IgE-mediated sensitization in less than one-third of

  9. Systematic Equation Formulation

    DEFF Research Database (Denmark)

    Lindberg, Erik

    2007-01-01

    A tutorial giving a very simple introduction to the set-up of the equations used as a model for an electrical/electronic circuit. The aim is to find a method which is as simple and general as possible with respect to implementation in a computer program. The “Modified Nodal Approach”, MNA, and th......, and the “Controlled Source Approach”, CSA, for systematic equation formulation are investigated. It is suggested that the kernel of the P Spice program based on MNA is reprogrammed....

  10. Analysis of novel meningococcal vaccine formulations.

    Science.gov (United States)

    Zughaier, Susu M

    2017-07-03

    The protective effect of meningococcal vaccines targeting disease causing serogroups exemplified by the introduction of MenAfriVac™ in Africa, is well established and documented in large population-based studies. Due to the emergence of other meningococcal disease causing serogroups, novel vaccine formulations are needed. There is a high potential for novel nanotechnology-based meningococcal vaccine formulations that can provide wider vaccine coverage. The proposed meningococcal vaccine formulation contains spherical shaped micro and nanoparticles that are biological mimics of Niesseria meningitidis, therefore present to immune system as invader and elicit robust immune responses. Vaccine nanoparticles encapsulate meningococcal CPS polymers in a biodegradable material that slowly release antigens, therefore enhance antigen presentation by exerting antigen depot effect. The antigenicity of meningococcal vaccine delivered in nanoparticles is significantly higher when compared to vaccine delivered in solution. Preclinical studies are required to assess the immunogenicity of novel vaccine formulations. Therefore, implementing various in-vitro human immune cell-based assays that mimic in-vivo interactions, would provide good insight on optimal antigen dose, effective antigen presentation, facilitate screening of various vaccine and adjuvant combinations and predict in-vivo immunogenicity. This rapid approach is cost-effective and provides data required for the preclinical immunogenicity assessment of novel meningococcal vaccine formulations.

  11. Geriatric-oriented high dose nutraceutical ODTs: Formulation and Physicomechanical characterization.

    Science.gov (United States)

    Agiba, Ahmed M; Abdel-Hamid, Sameh; Nasr, Maha; Geneidi, Ahmed S

    2017-03-20

    Oral disintegrating tablets (ODTs) represent a better option than conventional tablets for geriatric population, owing to their fast onset of action and their better patient compliance. Two principal therapeutic high-dose nutraceuticals; chondroitin sulphate and glucosamine were formulated into an oral disintegration tablet (ODT) intended for sublingual administration, and optimized to improve compliance and achieve rapid onset of action in osteoarthritis treatment. Different formulations were prepared either by melt granulation or direct compression techniques. Excipients at different ratios such as superdisintegrants, pharmaburstTM C1, spray-dried mannitol, and polyethylene glycols were used to enhance the disintegration time for the ODT systems. Although the ODT systems weighed around 1.3 gm with 60% drug load, some systems disintegrated within 2-3 min with 100% drug release. PharmaburstTM C1 turned out to be the key excipient responsible for the superdisintegration properties of the ODTs. Dissolution enhancement of the two nutraceuticals could be achieved compared to the marketed conventional tablets. The improved disintegration and dissolution properties of our prepared ODTs is expected to enhance the bioavailability of the high dose glucosamine and chondroitin sulphate in comparison with conventional tablets, which delineates them as a promising dosage form for the aforementioned nutraceuticals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Ether formulations of relativity

    Energy Technology Data Exchange (ETDEWEB)

    Duffy, M.C.

    1980-12-01

    Contemporary ether theories are surveyed and criticized, especially those formally identical to orthodox Relativity. The historical development of Relativity, Special and General, in terms of an ether, is briefly indicated. Classical interpretations of Generalized Relativity using ether are compared to Euclidean formulations using a background space. The history of a sub-group of theories, formulating a 'new' Relativity involving modified transforms, is outlined. According to the theory with which they agree, recent supposed detections of drift are classified and criticized. Cosmological evidence suggesting an ether is mentioned. Only ether theories formally identical to Relativity have been published in depth. They stand criticized as being contrary to the positivist spirit. The history of mechanical analogues is traced, from Hartley's representing gravitating matter as spherical standing waves, to recent suggestions that vortex-sponge might model electromagnetic, quantum, uncertainty and faster-than-light phenomena. Contemporary theories are particular physical theories, themselves 'second interpretations' of a primary mathematical model. Mechanical analogues are auxiliary, not necessary, to other theory, disclosing relationships between classical and non-classical descriptions of assemblies charging state. The ether-relativity polemic, part of a broader dispute about relativity, is founded on mistaken conceptions of the roles of mathematical and physical models, mechanical analogues; and a distored view of history, which indicates that ether theories have become relativistic. 103 references.

  13. Screening of mucoadhesive vaginal gel formulations

    Directory of Open Access Journals (Sweden)

    Ana Ochoa Andrade

    2014-12-01

    Full Text Available Rational design of vaginal drug delivery formulations requires special attention to vehicle properties that optimize vaginal coating and retention. The aim of the present work was to perform a screening of mucoadhesive vaginal gels formulated with carbomer or carrageenan in binary combination with a second polymer (carbomer, guar or xanthan gum. The gels were characterised using in vitroadhesion, spreadability and leakage potential studies, as well as rheological measurements (stress and frequency sweep tests and the effect of dilution with simulated vaginal fluid (SVF on spreadability. Results were analysed using analysis of variance and multiple factor analysis. The combination of polymers enhanced adhesion of both primary gelling agents, carbomer and carrageenan. From the rheological point of view all formulations presented a similar behaviour, prevalently elastic and characterised by loss tangent values well below 1. No correlation between rheological and adhesion behaviour was found. Carbomer and carrageenan gels containing the highest percentage of xanthan gum displayed good in vitro mucoadhesion and spreadability, minimal leakage potential and high resistance to dilution. The positive results obtained with carrageenan-xanthan gum-based gels can encourage the use of natural biocompatible adjuvants in the composition of vaginal products, a formulation field that is currently under the synthetic domain.

  14. Evaluating tretinoin formulations in the treatment of acne.

    Science.gov (United States)

    Kircik, Leon H

    2014-04-01

    Topical tretinoin has been a standard treatment for acne vulgaris for more than 4 decades. While tretinoin has demonstrated proven efficacy in the treatment of acne lesions, it also is associated with the potential for skin irritation. Newer formulations have been designed to optimize both the drug concentration and the delivery vehicle with the aim to enable clinicians to provide increasingly effective acne treatment that minimizes irritation. These therapies include formulations with varying concentrations of tretinoin and vehicles that utilize a microsponge delivery system, hydrogels and micronized tretinoin, or propolymers. The purpose of this review is to evaluate different formulations and combinations of tretinoin in the treatment of acne vulgaris. While these advanced formulations were designed for controlled release of active ingredient, and have the potential to reduce cutaneous irritation relative to standard tretinoin cream and gel formulations, there is a need for comparative studies to evaluate the relative benefits of each of these advanced tretinoin formulations in optimizing acne treatment.

  15. Efficacy and safety of sublingual immunotherapy for allergic rhinitis in pediatric patients: A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Feng, Bohai; Wu, Jueting; Chen, Bobei; Xiang, Haijie; Chen, Ruru; Li, Bangliang; Chen, Si

    2017-01-01

    Allergic rhinitis (AR) has become a global health problem that constantly affects a large part of the general population, especially children. Sublingual allergen immunotherapy (SLIT) has been used extensively for pediatric AR, although its efficacy and safety are often questioned. In this meta-analysis of randomized controlled trials (RCT), we evaluated the use of SLIT for pediatric AR. A number of medical literature data bases were searched through January 2016 to identify RCTs that examined the use of SLIT for pediatric AR and that assessed clinical outcomes related to efficacy. Descriptive and quantitative information was abstracted. Standardized mean differences (SMD) were calculated by using fixed- and random-effects models. Subgroup analyses were performed. Heterogeneity was assessed by using the I2 metric. A network meta-analysis was used to estimate SMDs between two SLIT protocols for pediatric seasonal AR. All data were extracted from publications or received from the authors. Twenty-six studies were eligible for inclusion in the meta-analysis of rhinitis or rhinoconjunctivitis symptom scores, and 19 studies were eligible for the meta-analysis of medication scores. Descriptive and quantitative data were extracted. SLIT differed significantly from placebo in terms of symptom scores (SMD -0.55 [95% confidence interval {CI}, -0.86 to -0.25]; p = 0.0003, I2 = 90%) and medication scores (SMD -0.67 [95% CI, -0.96 to -0.38]; p pediatric patients. Moreover, the safety of SLIT needs to be confirmed in RCTs with larger samples.

  16. Correlation between early sublingual small vessel density and late blood lactate level in critically ill surgical patients.

    Science.gov (United States)

    Yeh, Yu-Chang; Wang, Ming-Jiuh; Chao, Anne; Ko, Wen-Je; Chan, Wing-Sum; Fan, Shou-Zen; Tsai, Jui-Chang; Sun, Wei-Zen

    2013-04-01

    Surgical stress may cause excessive inflammation and lead to microcirculatory dysfunction. The hypothesis of this study was that early microcirculatory dysfunction may result in anaerobic glycolysis and lead to elevated blood lactate levels in patients admitted to surgical intensive care units. This prospective observational study enrolled adult patients admitted to surgical intensive care units after general surgery or thoracic surgery. We measured blood lactate levels before the operation and at 1 h and 24 h after the operation. We obtained images of sublingual microcirculation using a sidestream dark field video microscope and analyzed them employing automated analysis software. A total of 31 patients completed the study. Perioperative total and perfused small vessel densities were lower in patients with a blood lactate level ≥3 mmol/L. We observed a significant correlation between the total small vessel density at 1 h and the blood lactate level at 24 h (r = -0.573; P = 0.001). In addition, we saw a significant correlation between the perfused small vessel density at 1 h and the blood lactate level at 24 h (r = -0.476; P = 0.008). Early total and perfused small vessel density may be used as an early predictor or therapeutic goal for critically ill surgical patients in further studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Breakthrough Pain Management with Sublingual Fentanyl Tablets in Patients with Cancer: Age Subgroup Analysis of a Multicenter Prospective Study.

    Science.gov (United States)

    Guitart, Jordi; Vargas, María Isabel; De Sanctis, Vicente; Folch, Jordi; Salazar, Rafael; Fuentes, José; Coma, Joan; Ferreras, Julia; Moya, Jordi; Tomás, Albert; Estivill, Pere; Rodelas, Francisco; Jiménez, Antonio Javier; Sanz, Almudena

    2017-09-01

    Breakthrough pain (BTP) management in patients with cancer is challenging, especially in the elderly. However, no studies examining the influence of age on BTP medication have been conducted. The aim of this work was to investigate the effect of sublingual fentanyl tablets (SFTs) in terms of efficacy, safety, and quality of life in two age categories. We performed age subgroup analyses (Pain intensity (PI), onset of pain relief, frequency and duration of BTP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health-status instruments used were the Short Form 12, version 2 (SF-12v2) questionnaire, and the Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Twenty-six patients were aged 65 years. Most patients experienced one to five daily episodes after 30 days, and <5% needed a treatment change. AEs were less frequently reported in older individuals (20.5 vs. 36.4%). Age subgroup analyses suggest that SFTs are an effective and safe treatment for the management of BTP in cancer patients of all ages. SFTs may offer a well-tolerated and efficient option to control cancer BTP in the elderly.

  18. Determination of degradation products and process related impurities of asenapine maleate in asenapine sublingual tablets by UPLC

    Science.gov (United States)

    Kumar, Nitin; Sangeetha, D.; Kalyanraman, L.

    2017-11-01

    For determination of process related impurities and degradation products of asenapine maleate in asenapine sublingual Tablets, a reversed phase, stability indicating UPLC method was developed. Acetonitrile, methanol and potassium dihydrogen phosphate buffer with tetra-n- butyl ammonium hydrogen sulphate as ion pair (pH 2.2; 0.01 M) at flow rate of 0.2 ml/min were used in gradient elution mode. Separation was achieved by using acquity BEH Shield RP18 column (1.7 μm, 2.1 mm×100 mm) at 35 ºC. UV detection was performed at 228 nm. Subsequently the liquid chromatography method was validated as per ICH. The drug product was exposed to the stress conditions of acid hydrolysis, base hydrolysis, water hydrolysis, oxidative, thermal, and photolytic. In oxidative stress and thermal stress significant degradation was observed. All the degradation products were well separated from analyte peak and its impurities. Stability indicating nature of the method was proved by demonstrating the peak purity of Asenapine peak in all the stressed samples. The mass balance was found >95% for all the stress conditions. Based on method validation, the method was found specific, linear, accurate, precise, rugged and robust.

  19. Cost-effectiveness analysis of oral fentanyl formulations for breakthrough cancer pain treatment.

    Science.gov (United States)

    Cortesi, Paolo Angelo; D'Angiolella, Lucia Sara; Vellucci, Renato; Allegri, Massimo; Casale, Giuseppe; Favaretti, Carlo; Kheiraoui, Flavia; Cesana, Giancarlo; Mantovani, Lorenzo Giovanni

    2017-01-01

    Breakthrough cancer Pain (BTcP) has a high prevalence in cancer population. Patients with BTcP reported relevant health care costs and poor quality of life. The study assessed the cost-effectiveness of the available Oral Fentanyl Formulations (OFFs) for BTcP in Italy. A decision-analytical model was developed to estimate costs and benefits associated with treatments, from the Italian NHS perspective. Expected reductions in pain intensity per BTcP episodes were translated into, percentage of BTcP reduction, resource use and Quality-Adjusted-Life-Years (QALYs). Relative efficacy, resources used and unit costs data were derived from the literature and validated by clinical experts. Probabilistic and deterministic sensitivity analyses were performed. At base-case analysis, Sublingual Fentanyl Citrate (FCSL) compared to other oral formulations reported a lower patient's cost (€1,960.8) and a higher efficacy (18.7% of BTcP avoided and 0.0507 QALYs gained). The sensitivity analyses confirmed the main results in all tested scenarios, with the highest impact reported by BTcP duration and health care resources consumption parameters. Between OFFs, FCSL is the cost-effective option due to faster reduction of pain intensity. However, new research is needed to better understand the economic and epidemiologic impact of BTcP, and to collect more robust data on economic and quality of life impact of the different fentanyl formulations. Different fentanyl formulations are available to manage BTcP in cancer population. The study is the first that assesses the different impact in terms of cost and effectiveness of OFFs, providing new information to better allocate the resources available to treat BTcP and highlighting the need of better data.

  20. Olaparib tablet formulation

    DEFF Research Database (Denmark)

    Plummer, Ruth; Swaisland, Helen; Leunen, Karin

    2015-01-01

    formulation. METHODS: PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed. In Part B, patients received olaparib tablets (300 mg bid) for 5 days under fasting conditions; in Part...... C, patients were allowed continued access to olaparib. Safety was assessed throughout, with data reported for Parts A and B. RESULTS: A total of 60 and 56 patients were evaluable for safety and PK analyses, respectively; 57 patients entered Part B. Rate of olaparib absorption was slower.......16)]. The point estimate and 90 % CI for the AUC0-∞ treatment ratio were within pre-defined bioequivalence limits (0.80-1.25). Adverse event data were consistent with the known safety profile of olaparib. CONCLUSIONS: Results of this study showed that a high-fat meal decreases the rate of absorption and peak...

  1. Impacto do sildenafil sublingual na hipertensão pulmonar de pacientes com insuficiência cardíaca Impacto del sildenafil sublingual en la hipertensión pulmonar de pacientes con insuficiencia cardiaca Impact of sublingual sildenafil on pulmonary hypertension in patients with heart failure

    Directory of Open Access Journals (Sweden)

    Aguinaldo Figueiredo de Freitas Jr.

    2009-02-01

    Full Text Available FUNDAMENTO: A hipertensão pulmonar (HP é fator de mau prognóstico no pós-operatório de transplante cardíaco (TC e, desta forma, o estudo do grau de reversibilidade a vasodilatadores é obrigatório durante avaliação pré-operatória. OBJETIVO: Avaliar os efeitos hemodinâmicos pulmonares e sistêmicos do sildenafil como droga vasodilatadora durante o teste de reversibilidade da HP em candidatos a transplante cardíaco. MÉTODOS: Pacientes em fila para TC foram submetidos à medida de variáveis hemodinâmicas sistêmicas e pulmonares antes e após a administração de 100mg dose única e sublingual de sildenafil, durante cateterização cardíaca direita. RESULTADOS: Quatorze pacientes (idade: 47±12 anos, 71,4% homens com insuficiência cardíaca avançada, Fração de Ejeção (FE 25 ± 7%, Classe Funcional (CF- NYHA CF III - 6 e CF IV - 8, foram avaliados neste estudo. A administração aguda de sildenafil mostrou ser eficaz na redução das pressões sistólica (62,4 ± 12,1 vs. 51,5 ± 9,6 mmHg, IC=95%, pFUNDAMENTO: La hipertensión pulmonar (HP se muestra factor de mal pronóstico en el postoperatorio de transplante cardiaco (TC y, de esta forma, el estudio del grado de reversibilidad a vasodilatadores se vuelve obligatorio durante evaluación preoperatoria. OBJETIVO: Evaluar los efectos hemodinámicos pulmonares y sistémicos del Sildenafil como droga vasodilatadora durante la prueba de reversibilidad de la HP en candidatos a transplante cardiaco. MÉTODOS: Pacientes en fila para TC fueron sometidos a la medición de variables hemodinámicas sistémicas y pulmonares, antes y luego de la administración de 100mg en dosificación única y sublingual de Sildenafil, durante cateterización cardiaca derecha. RESULTADOS: Se evaluaron en este estudio a 14 pacientes (edad: 47±12 años, el 71,4% varones con insuficiencia cardiaca avanzada, fracción de eyección (FE 25 ± 7%, clase funcional (CF-NYHA CF III - 6 y CF IV - 8. La

  2. Novel Δ9-tetrahydrocannabinol formulation Namisol® has beneficial pharmacokinetics and promising pharmacodynamic effects

    Science.gov (United States)

    Klumpers, Linda E; Beumer, Tim L; van Hasselt, Johan G C; Lipplaa, Astrid; Karger, Lennard B; Kleinloog, H Daniël; Freijer, Jan I; de Kam, Marieke L; van Gerven, Joop M A

    2012-01-01

    AIMS Among the main disadvantages of currently available Δ9-tetrahydrocannabinol (THC) formulations are dosing difficulties due to poor pharmacokinetic characteristics. Namisol® is a novel THC formulation, designed to improve THC absorption. The study objectives were to investigate the optimal administration route, pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of Namisol®. METHODS This first in human study consisted of two parts. Panel I included healthy males and females (n = 6/6) in a double-blind, double-dummy, randomized, crossover study with sublingual (crushed tablet) and oral administration of Namisol® (5 mg THC). Based on these results, male and female (n = 4/5) participants from panel I received oral THC 6.5 and 8.0 mg or matching placebo in a randomized, crossover, rising dose study during panel II. PD measurements were body sway; visual analogue scales (VAS) mood, psychedelic and heart rate. THC and 11-OH-THC population PK analysis was performed. RESULTS Sublingual administration showed a flat concentration profile compared with oral administration. Oral THC apparent t1/2 was 72–80 min, tmax was 39–56 min and Cmax 2.92–4.69 ng ml−1. THC affected body sway (60.8%, 95% CI 29.5, 99.8), external perception (0.078 log mm, 95% CI 0.019, 0.137), alertness (−2.7 mm, 95% CI −4.5, −0.9) feeling high (0.256 log mm, 95% CI 0.093, 0.418) and heart rate (5.6 beats min–1, 95% CI 2.7, 6.5). Namisol® was well tolerated. CONCLUSIONS Oral Namisol® showed promising PK and PD characteristics. Variability and tmax of THC plasma concentrations were smaller for Namisol® than reported for studies using oral dronabinol and nabilone. This study was performed in a limited number of healthy volunteers. Therefore, future research on Namisol® should study clinical effects in patient populations. PMID:22680341

  3. Plutonium Immobilization Project Baseline Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Ebbinghaus, B.

    1999-02-01

    A key milestone for the Immobilization Project (AOP Milestone 3.2a) in Fiscal Year 1998 (FY98) is the definition of the baseline composition or formulation for the plutonium ceramic form. The baseline formulation for the plutonium ceramic product must be finalized before the repository- and plant-related process specifications can be determined. The baseline formulation that is currently specified is given in Table 1.1. In addition to the baseline formulation specification, this report provides specifications for two alternative formulations, related compositional specifications (e.g., precursor compositions and mixing recipes), and other preliminary form and process specifications that are linked to the baseline formulation. The preliminary specifications, when finalized, are not expected to vary tremendously from the preliminary values given.

  4. Baseline LAW Glass Formulation Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, Albert A. [USDOE Office of River Protection, Richland, WA (United States); Mooers, Cavin [The Catholic University of America, Washington, DC (United States). Vitreous State Lab.; Bazemore, Gina [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Pegg, Ian L. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Hight, Kenneth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Lai, Shan Tao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Buechele, Andrew [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Rielley, Elizabeth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Gan, Hao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Muller, Isabelle S. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Cecil, Richard [The Catholic University of America, Washington, DC (United States). Vitreous State Lab

    2013-06-13

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements.

  5. Effect of Two Years of Treatment with Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at Three Years among Patients with Moderate to Severe Seasonal Allergic Rhinitis: A Randomized Clinical Trial

    Science.gov (United States)

    Scadding, Guy W.; Calderon, Moises A.; Shamji, Mohamed H.; Eifan, Aarif O.; Penagos, Martin; Dumitru, Florentina; Sever, Michelle L.; Bahnson, Henry T; Lawson, Kaitie; Harris, Kristina M.; Plough, Audrey G.; Panza, Joy Laurienzo; Qin, Tielin; Lim, Noha; Tchao, Nadia K.; Togias, Alkis; Durham, Stephen R.

    2017-01-01

    Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least two years following discontinuation of treatment. Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy compared with placebo provides improved nasal response to allergen challenge at 3 year follow-up. Design, Setting, Participants A randomized double-blind, placebo-controlled, 3-parallel group study performed in a single academic centre, Imperial College London, including adult patients with moderate-to-severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrolment was March 2011, last follow-up February 2015. Intervention Thirty-six participants received 2 years sublingual immunotherapy (daily tablets containing 15 microgram of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 micrograms of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years and at 3 years (1 year after treatment discontinuation). Main outcomes and measures Total nasal symptom scores (TNSS, range 0 (best) to 12 (worst) were recorded during 0–10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy to placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Results Among 106 participants who were randomized (mean age 33.5 years, 32.1% female), 92 completed the study at 3 years. Imputed TNSS scores [mean (95% confidence intervals)] pre-treatment and

  6. Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial.

    Science.gov (United States)

    Scadding, Guy W; Calderon, Moises A; Shamji, Mohamed H; Eifan, Aarif O; Penagos, Martin; Dumitru, Florentina; Sever, Michelle L; Bahnson, Henry T; Lawson, Kaitie; Harris, Kristina M; Plough, Audrey G; Panza, Joy Laurienzo; Qin, Tielin; Lim, Noha; Tchao, Nadia K; Togias, Alkis; Durham, Stephen R

    2017-02-14

    Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5

  7. Accelerating Vaccine Formulation Development Using Design of Experiment Stability Studies.

    Science.gov (United States)

    Ahl, Patrick L; Mensch, Christopher; Hu, Binghua; Pixley, Heidi; Zhang, Lan; Dieter, Lance; Russell, Ryann; Smith, William J; Przysiecki, Craig; Kosinski, Mike; Blue, Jeffrey T

    2016-10-01

    Vaccine drug product thermal stability often depends on formulation input factors and how they interact. Scientific understanding and professional experience typically allows vaccine formulators to accurately predict the thermal stability output based on formulation input factors such as pH, ionic strength, and excipients. Thermal stability predictions, however, are not enough for regulators. Stability claims must be supported by experimental data. The Quality by Design approach of Design of Experiment (DoE) is well suited to describe formulation outputs such as thermal stability in terms of formulation input factors. A DoE approach particularly at elevated temperatures that induce accelerated degradation can provide empirical understanding of how vaccine formulation input factors and interactions affect vaccine stability output performance. This is possible even when clear scientific understanding of particular formulation stability mechanisms are lacking. A DoE approach was used in an accelerated 37(°)C stability study of an aluminum adjuvant Neisseria meningitidis serogroup B vaccine. Formulation stability differences were identified after only 15 days into the study. We believe this study demonstrates the power of combining DoE methodology with accelerated stress stability studies to accelerate and improve vaccine formulation development programs particularly during the preformulation stage. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Clinical review: Clinical imaging of the sublingual microcirculation in the critically ill - where do we stand?

    NARCIS (Netherlands)

    R. Bezemer (Rick); S.A. Bartels (Sebastiaan); J. Bakker (Jan); C. Ince (Can)

    2012-01-01

    textabstractA growing body of evidence exists associating depressed microcirculatory function and morbidity and mortality in a wide array of clinical scenarios. It has been suggested that volume replacement therapy using fluids and/or blood in combination with vasoactive agents to modulate macro-

  9. Formulation Design of Dry Powders for Inhalation.

    Science.gov (United States)

    Weers, Jeffry G; Miller, Danforth P

    2015-10-01

    Drugs for inhalation are no longer exclusively highly crystalline small molecules. They may also be amorphous small molecules, peptides, antibodies, and myriad types of engineered proteins. The evolution of respiratory therapeutics has created a need for flexible formulation technologies to engineer respirable particles. These technologies have enabled medicinal chemists to focus on molecular design without concern regarding compatibility of physicochemical properties with traditional, blend-based technologies. Therapeutics with diverse physicochemical properties can now be formulated as stable and respirable dry powders. Particle engineering technologies have also driven the deployment of new excipients, giving formulators greater control over particle and powder properties. This plays a key role in enabling efficient delivery of drugs to the lungs. Engineered powder and device combinations enable aerosols that largely bypass the mouth and throat, minimizing the inherent variability among patients that arises from differences in oropharyngeal and airway anatomies and in breathing profiles. This review explores how advances among molecules, particles, and powders have transformed inhaled drug product development. Ultimately, this scientific progress will benefit patients, enabling new classes of therapeutics to be formulated as dry powder aerosols with improved efficacy, reduced variability and side effects, and improved patient adherence. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. An open-label, multicenter, phase I trial of a cremophor-free, polymeric micelle formulation of paclitaxel combined with carboplatin as a first-line treatment for advanced ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG-3016).

    Science.gov (United States)

    Lee, Shin Wha; Kim, Yong Man; Kim, Young Tae; Kang, Soon Beom

    2017-05-01

    This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer. This open-label, multicenter, phase I, dose-escalation study included 18 patients (median age: 59.0 years, range: 40-75 years) diagnosed with advanced epithelial ovarian cancer. All patients had measurable residual disease after debulking surgery. Patients were assigned to groups (n=6 each group) that received different doses of Genexol-PM (220, 260, and 300 mg/m², once every 3 weeks) and 5 area under the curve (AUC) carboplatin. Safety and efficacy were analyzed for each dose group. In this intention-to-treat population, 3 out of 18 patients dropped out of the study: 1 due to dose-limiting toxicity (DLT), 1 due to hypersensitivity, and 1 was lost during follow-up. DLTs were not reported at 220 mg/m² or 260 mg/m², but at 300 mg/m², 1 patient experienced DLT (grade 3 general pain). The MTD of Genexol-PM was not determined, but a dose of 300 mg/m² or less could be recommended for the phase II study. Most patients (73.9%) with adverse events recovered without sequelae, and no death occurred that was related to the disease or treatment. The best overall response rate was 94.1%. Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer. Based on these results, we recommended a dose of 300 mg/m² or less for a phase II study.

  11. Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial.

    Science.gov (United States)

    Pajno, G B; Passalacqua, G; Vita, D; Caminiti, L; Parmiani, S; Barberio, G

    2004-08-01

    The use of immunotherapy in asthmatic children is still controversial. Sublingual immunotherapy (SLIT) may represent an advance, due to the good safety profile, but little is known about its effects on lung function and nonspecific bronchial responsiveness. The aim of this study was to assess the effects of SLIT on these parameters, in children with Parietaria pollen-induced asthma. Thirty children with asthma solely due to Parietaria who participated in a previous randomized, placebo-controlled trial with SLIT were studied: pulmonary function test and methacholine challenge were carried out at baseline in winter 1999 (out season), during the 1999 season (before randomization), and during the 2001 season. Before randomization, there was a significant fall in methacholine provocation concentration during the pollen season vs baseline in both groups (SLIT group 9.78 +/- 5.95 mg/ml vs 3.37 +/- 2.99 mg/ml; placebo 8.70 +/- 6.25 mg/ml vs 2.44 +/- 2.25 mg/ml; P =.005). In the second pollen season, the response to methacholine returned to baseline values in the active group (9.10 +/- 7.7 mg/ml; P = NS vs baseline), whereas in the placebo group a significant increase in reactivity was still present (2.46 +/- 2.26; P = 0.008 vs baseline). No significant difference in FEV(1) and FEF(25-75) between the two groups was observed at all times. Our data show that SLIT abrogates the seasonal bronchial hyperreactivity in children with asthma due to Parietaria. This may be regarded as an indirect evidence of the effect on bronchial inflammation.

  12. Changes in cytokine profiles following treatment with food allergen-specific sublingual immunotherapy in dogs with adverse food reactions.

    Science.gov (United States)

    Maina, Elisa; Devriendt, Bert; Cox, Eric

    2017-12-01

    Food allergen-specific sublingual immunotherapy (FA-SLIT) is considered to be a novel, safe and effective approach in dogs with adverse food reactions (AFR). To investigate changes in key cytokines associated with FA-SLIT. Eleven dogs with confirmed AFR. Participants received either dose escalation of FA-SLIT or placebo over a six month period. Oral food challenge was performed at the beginning and end of the study, along with clinical examinations and collection of skin surface bacterial cytology and blood. Peripheral blood mononuclear cells were stimulated with the culprit food antigen. ELISA methods were used to quantify Interleukin (IL)-10, IFN-γ, IL-4 and IL-17A in the supernatant of stimulated cells. IL-10 and IFN-γ levels were significantly increased at the end of the study in the treatment group (T), compared with the placebo group (P), whereas no changes were found in IL-4 levels. IL-17A levels were decreased in both groups (but more profoundly in T). Bacterial scores on the skin were positively correlated with IL-17A and inversely correlated with IL-10 concentrations. Interleukins were not correlated with clinical scores. FA-SLIT may modulate the allergic response toward Th1 and Treg cell phenotypes, and induction of tolerance in dogs with AFR. Therefore, FA-SLIT may be a tool to desensitize dogs with AFR. However, more data on a larger number of cases and a broader panel of cytokines are needed to corroborate these findings, and to elucidate the mechanism of action for responses to FA-SLIT by dogs with AFR. © 2017 ESVD and ACVD.

  13. Sublingual Fentanyl Tablets for Relief of Breakthrough Pain in Cancer Patients and Association with Quality-of-Life Outcomes.

    Science.gov (United States)

    Guitart, Jordi; Vargas, María Isabel; De Sanctis, Vicente; Folch, Jordi; Salazar, Rafael; Fuentes, José; Coma, Jordi; Ferreras, Julia; Moya, Jordi; Tomás, Albert; Estivill, Pere; Rodelas, Francisco; Jiménez, Antonio Javier

    2015-12-01

    Breakthrough pain (BTP) is highly prevalent in patients with cancer and is strongly associated with adverse outcomes related to health status, mood, anxiety and depression. However, studies on the effect of BTP medication on quality of life (QOL) are lacking. The purpose of this study was to provide a qualitative evaluation of the effect of sublingual fentanyl tablets (SFT), a therapy specifically developed for BTP, on the QOL of cancer pain patients. We conducted a multicentre, prospective observation post-authorisation, open-label study between March and December 2013. The study consisted of a screening visit and four assessment points at 3, 7, 15 and 30 days. Pain intensity (PI), frequency of BTP, onset of pain relief and adverse events (AEs) were assessed at each visit. Anxiety and depression were evaluated using the validated Hospital Anxiety and Depression Scale (HADS) and health status using the Short Form 12, version 2 (SF-12v2) Health Survey. Of the 102 patients considered eligible, 81 (79.4 %) were enrolled; of these, 69 (85.1 %) completed the study. Significant pain reduction was achieved for average PI (p < 0.001) compared with baseline. At the end of the observational period, HADS scores showed significant improvement in the depression subscale (p = 0.005) and the anxiety subscale (p < 0.001). Similarly, SF-12 scores showed significant improvement, both in the mental component score (p < 0.001) and the physical component score (p = 0.002). SFT was well-tolerated and only one patient withdrew from the study due to drug-related AEs. SFT represents an effective, well-tolerated treatment for cancer BTP. Results provide consistent evidence for the positive impact of SFT on health-related QOL and physical functioning as well as other co-morbidities of cancer BTP such as anxiety and depression.

  14. Efficacy of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis: A Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Feng, Bohai; Xiang, Haijie; Jin, Haiyong; Gao, Jinjian; Huang, Saiyu; Shi, Yunbin; Chen, Ruru

    2017-01-01

    Purpose Allergic rhinitis (AR) has become a global issue for a large part of the general population. Sublingual immunotherapy (SLIT) has been used extensively to treat persistent allergic rhinitis (PAR). Although systematic reviews have confirmed the effectiveness of SLIT for the treatment of AR, a considerable number of studies using extracts of house dust mites (HDMs) for immunotherapy found no consensus on basic treatment parameters and questioned the efficacy of SLIT. Methods In this study, we evaluated SLIT for PAR by a meta-analysis of randomized controlled trials (RCTs). Medline, Embase, and Cochrane Library database searches were performed for RCTs on the treatment of PAR by SLIT that assessed clinical outcomes related to efficacy through May 2016. Descriptive and quantitative information was abstracted. An analysis was performed with standardized mean differences (SMDs) under a fixed or random effects model. Subgroup analyses were performed. Heterogeneity was assessed using the I2 metric. Results In total, 25 studies were eligible for inclusion in the meta-analysis for symptom scores and 15 studies for medication scores. SLIT was significantly different from the controls for symptom scores (SMD=1.23; 95% confidence interval [CI]=1.74 to 0.73; P<0.001). For medication scores, significant differences for SLIT were also observed versus the controls (SMD=-1.39; 95% CI=-1.90 to -0.88; P<0.001). Conclusions Our meta-analysis indicates that SLIT provided significant symptom relief and reduced the need for medications in PAR. In this study, significant evidence was obtained despite heterogeneity with regard to the use of mite extract. Specifically, the mite extract used was provided by the patients with PAR. Furthermore, to confirm both the objective outcomes and the effective doses of HDM allergen extracts, experimental data should be obtained from large high-quality population-based studies. PMID:28293928

  15. The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis.

    Science.gov (United States)

    Compalati, E; Passalacqua, G; Bonini, M; Canonica, G W

    2009-11-01

    Recent meta-analyses documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) and asthma (AA). Although SLIT appeared globally effective, the sub-analyses for single allergens provided uncertain results. This study is aimed to investigate the efficacy of SLIT with house dust mite (HDM) extracts in AR and AA through an updated reassessment of randomized controlled trials. Electronic databases were searched up to March 31, 2008, for randomized DBPC trials, assessing the efficacy of SLIT in AR and AA due to HDM sensitization. Outcomes were symptom scores and rescue medications use. For AR, eight studies fulfilled the selection criteria. A significant reduction in symptoms of AR (SMD -0.95; CI 95%-1.77 to -0.14 P = 0.02) was found in 194 patients (adults and children) receiving SLIT compared to 188 receiving placebo. For AA, with nine studies, similar results were found for symptoms (SMD -0.95; CI 95%-1.74 to -0.15 P = 0.02) in 243 patients (adults and children) receiving SLIT compared to 209 receiving placebo. A reduction in rescue medication use was found for AR (SMD -1.88; CI 95%-3.65 to -0.12 P = 0.04) in 89 patients, and AA (SMD -1.48; CI 95%-2.70 to -0.26 P = 0.02) in 202 patients. A relevant inter-study heterogeneity was detected. Promising evidence of efficacy for SLIT, using mite extract in allergic patients suffering from AR and AA, are herein shown. These findings suggest that more data are needed, derived from large-population-based high quality studies, and corroborated by objective outcomes, mainly for AA.

  16. Sublingual Buprenorphine and Methadone Maintenance Treatment: A Three-Year Follow-Up of Quality of Life Assessment

    Directory of Open Access Journals (Sweden)

    Salvatore M. Giacomuzzi

    2005-01-01

    Full Text Available This study was conducted to compare long-term outcome effects on the quality of life (QOL of oral methadone with sublingual buprenorphine maintenance treatment. The QOL status of opioid-dependent patients was assessed using the German version (“Berlin Quality of Life Profile” of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opiate Withdrawal Scale (OWS. Urine tests were carried out randomly to detect additional consumption. In the first study period, 53 opioid-dependent subjects were enrolled and 25 could be reached after 3 years. The retention rate was 50% for methadone and 45% for buprenorphine (p = 0.786. Baseline values of the total sample (completers and noncompleters QOL and somatic complaints did not show significant differences between the two treatment groups. QOL characteristics at 6 months of treatment of the buprenorphine completer and noncompleter groups differed significantly regarding job (p = 0.013, family, and total score of physical symptoms (p = 0.002, in which the completer group showed the more favorable values. Concerning physical symptoms at 36 months, logistic regression revealed significantly less stomach cramps (p = 0.037 and fatigue and tiredness (p = 0.034 in buprenorphine compared to the methadone. Moreover, the buprenorphine-maintained group showed significantly less additional consumption of benzodiazepines (p = 0.015 compared with methadone participants. It is concluded that opioid addicts improved their QOL and health status when treated with methadone or buprenorphine. In summary, regarding QOL and health status, the present data indicate that buprenorphine is also a useful long-term alternative for maintenance treatment of opioid-dependent patients.

  17. Cine MR enterography grading of small bowel peristalsis: evaluation of the antiperistaltic effectiveness of sublingual hyoscyamine sulfate.

    Science.gov (United States)

    Ghobrial, Peter M; Neuberger, Ilana; Guglielmo, Flavius F; Mitchell, Donald G; Parker, Laurence; O'Kane, Patrick L; Roth, Christopher G; Deshmukh, Sandeep P; Borowski, Allison

    2014-01-01

    To use a cine balanced steady-state free precession magnetic resonance enterography (cine MRE) pulse sequence to assess the effectiveness of a sublingual (SL) antiperistaltic agent, hyoscyamine sulfate. Institutional review board approval was granted with an exemption for informed consent in this Health Insurance Portability and Accountability Act-compliant, retrospective, single-institution study. Of the 288 MRE examinations performed between October 1, 2007 and January 15, 2011, 92 using SL hyoscyamine sulfate for antiperistalsis were included for review, each with cine MRE before and after medication. These 184 cine MRE data sets were randomized, blinded for treatment, and independently reviewed by five attending abdominal radiologists, who rated the degree of whole abdomen bowel motility on each cine MRE data set on a 5-point scale. Pre- and postmedication mean peristalsis ratings, standard deviation, mean difference, and treatment effect sizes were calculated. A repeated measures analysis of variance test was performed using a significance threshold of P = .05. Interobserver reliabilities were also calculated. Mean peristalsis ratings ranged 2.63-3.34 and 2.36-3.03, before and after medication administration, respectively. The mean differences ranged from 0.22 to 0.46, which are treatment effect sizes of 0.20 to 0.37. The decrease in peristalsis observed by the five reviewing radiologists after SL hyoscyamine sulfate administration was significant (df = 1/182, f = 7.35, P cine MRE sequences show decreased bowel peristalsis after the use of SL hyoscyamine sulfate, the small size of the observed treatment effect is likely insufficient to justify its use for MRE. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  18. Cost-minimization analysis of sublingual immunotherapy versus subcutaneous immunotherapy for house dust mite respiratory allergic disease in Denmark.

    Science.gov (United States)

    Rønborg, Steen; Johnsen, Claus R; Theilgaard, Sune; Winther, Anders; Hahn-Pedersen, Julie; Andreasen, Jakob Nørgaard; Olsen, Jens

    2016-08-01

    Objectives Currently, patients with persistent moderate-to-severe house dust mite (HDM) allergic rhinitis despite use of symptom-relieving medication can be offered subcutaneously administered allergy immunotherapy (SQ SCIT; Alutard SQ) as standard care of treatment in Denmark. Recently, a HDM sublingually administered allergy immunotherapy tablet (SQ SLIT-tablet; ACARIZAX) has been developed for at-home treatment. The purpose of this analysis is to compare the costs related to treatment and administration of SQ SLIT-tablet and SQ SCIT. Methods Assuming equal efficacy between ther SQ SLIT-tablet and SQ SCIT, the cost-minimization analysis was the most appropriate for the comparison. According to guidelines and Summary of Product Characteristics, the treatment duration of SQ SLIT-tablet is 3 years and 3-5 years for SQ SCIT. The courses of treatment vary among patients and, therefore, the costs of treatment have been calculated for an average patient with HDM respiratory allergic disease (RAD) receiving either SQ SLIT-tablet or SQ SCIT. All costs associated with allergy immunotherapy were collected, i.e., cost of medication, administration and treatment setting, and discounted according to Danish guidelines. Comprehensive univariate sensitivity analyses were carried out. Results The treatment costs for an average patient with HDM RAD are €3094 for SQ SLIT-tablet and €3799 for SQ SCIT; however, when adding indirect costs to the calculations the total costs of the treatments are €3697 and €6717 for SQ SLIT-tablet and SQ SCIT, respectively. Therefore, if 2500 patients with HDM RAD were treated with SQ SLIT-tablet instead of SQ SCIT, it would elicit a saving to the healthcare system of ∼€1.8 million. The conclusion was robust to any changes in the sensitivity analysis. Conclusion With regards to the cost of treating Danish patients with HDM RAD, it is clearly cost-saving to treat patients with SQ SLIT-tablet compared to SQ SCIT.

  19. Efficacy and safety of house dust mite sublingual immunotherapy in monosensitized and polysensitized children with respiratory allergic diseases.

    Science.gov (United States)

    Li, Peng; Li, Qi; Huang, Zhenghua; Chen, Wenbo; Lu, Yueqian; Tian, Man

    2014-10-01

    The efficacy of single-allergen-specific immunotherapy in polysensitized subjects is a matter of debate. This study aimed to investigate the efficacy of house dust mite (HDM) sublingual immunotherapy (SLIT) in monosensitized and polysensitized children. A total of 112 children, aged 4 to 13 years old, with HDM-induced respiratory allergic diseases were allocated to a monosensitized group (n = 56) or a polysensitized group (n = 56). Both groups were treated by standard pharmacotherapy and SLIT with Dermatophagoides farinae (American HDM) extracts for 52 weeks. Symptoms, medications, visual analogue scale (VAS), and presence of adverse events (AEs) were assessed once a month. Skin-prick test (SPT) was done before and after treatment. After treatment, subjects in the polysensitized group who completed the study were further analyzed as subgroup 1 (n = 20) and subgroup 2 (n = 15) according to the number of coexisting allergens. Forty-one subjects in the monosensitized group and 35 subjects in the polysensitized group completed the study. The global clinical parameters had significantly improved after treatment, with no significant difference between the monosensitized and polysensitized group throughout this period (all p > 0.05). The comparison among the monosensitized group, subgroup 1, and subgroup 2 indicated that there was no significant difference in symptoms scores and VAS at each scheduled follow-up visit. There was also no significant difference in total medications score (TMS) in the monosensitized group, subgroup 1, and subgroup 2 after week 24 (all p > 0.05). No severe systemic AEs were reported. No significant difference was observed in the clinical effects of HDM SLIT between polysensitized and monosensitized children with respiratory allergic diseases. © 2014 ARS-AAOA, LLC.

  20. OPTIMIZATION OF DIRECT COMPRESSION TABLET FORMULATIONS FOR USE IN TROPICAL COUNTRIES

    NARCIS (Netherlands)

    BOS, CE; BOLHUIS, GK; LERK, CF; DEBOER, JH; DUINEVELD, CAA; SMILDE, AK; DOORNBOS, DA

    1991-01-01

    With the aid of a combined mixture- and factorial- design, 2 standard tablet formulations were selected suitable for use in tropical countries. The formulations were based on native ingredients or ingredients that are available worldwide. The selection of the standard formulations was based on both

  1. Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2014-08-01

    Full Text Available Krishna Devarakonda,1 Terri Morton,1 Rachel Margulis,2 Michael Giuliani,3 Thomas Barrett4 1Clinical Pharmacology and Pharmacokinetics, 2Clinical Operations, 3Research and Development, 4Clinical Affairs, Mallinckrodt Inc., Hazelwood, MO, USA Background: XARTEMIS™ XR (formerly MNK-795 is a combination oxycodone (OC and acetaminophen (APAP analgesic with both immediate-release and extended-release (ER components (ER OC/APAP. The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets versus fasted conditions on the PK of ER OC/APAP was performed. Methods: This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48 were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results: Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC] from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion: The findings from this study suggest that ER OC

  2. Saltstone Clean Cap Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C

    2005-04-22

    The current operation strategy for using Saltstone Vault 4 to receive 0.2 Ci/gallon salt solution waste involves pouring a clean grout layer over the radioactive grout prior to initiating pour into another cell. This will minimize the radiating surface area and reduce the dose rate at the vault and surrounding area. The Clean Cap will be used to shield about four feet of Saltstone poured into a Z-Area vault cell prior to moving to another cell. The minimum thickness of the Clean Cap layer will be determined by the cesium concentration and resulting dose levels and it is expected to be about one foot thick based on current calculations for 0.1 Ci Saltstone that is produced in the Saltstone process by stabilization of 0.2 Ci salt solution. This report documents experiments performed to identify a formulation for the Clean Cap. Thermal transient calculations, adiabatic temperature rise measurements, pour height, time between pour calculations and shielding calculations were beyond the scope and time limitations of this study. However, data required for shielding calculations (composition and specific gravity) are provided for shielding calculations. The approach used to design a Clean Cap formulation was to produce a slurry from the reference premix (10/45/45 weight percent cement/slag/fly ash) and domestic water that resembled as closely as possible the properties of the Saltstone slurry. In addition, options were investigated that may offer advantages such as less bleed water and less heat generation. The options with less bleed water required addition of dispersants. The options with lower heat contained more fly ash and less slag. A mix containing 10/45/45 weight percent cement/slag/fly ash with a water to premix ratio of 0.60 is recommended for the Clean Cap. Although this mix may generate more than 3 volume percent standing water (bleed water), it has rheological, mixing and flow properties that are similar to previously processed Saltstone. The recommended

  3. Formulation of supergravity without superspace

    CERN Document Server

    Ferrara, S

    1979-01-01

    Supergravity, the particle theory which unifies under a unique gauge principle the quantum-mechanical concept of spin and space-time geometry, is formulated in terms of quantities defined over Minkowski space-time. 'l'he relation between this formulation and the fonnulation which uses superspace, the space-time supplemented by spinning degrees of freedom, is also briefly discussed.

  4. Biopsychosocial Formulation: Recognizing Educational Shortcomings

    Science.gov (United States)

    McClain, Tina; O'Sullivan, Patricia S.; Clardy, James A.

    2004-01-01

    Objective: Since Engel introduced the biopsychosocial model, it has been extensively examined. The authors expect psychiatrists to formulate cases using the biopsychosocial model. However, resident psychiatrists' ability to generate formulations using this model has received little attention. Methods: The authors evaluated resident biopsychosocial…

  5. Simultaneously Exploiting Two Formulations: an Exact Benders Decomposition Approach

    DEFF Research Database (Denmark)

    Lusby, Richard Martin; Gamst, Mette; Spoorendonk, Simon

    . Furthermore, it proves the correctness of the procedure and considers how to include interesting extensions such as cutting planes and advanced branching strategies. Finally, we test and compare the performance of the proposed approach on publicly available instances of the Bin Packing problem. Compared......When modelling a given problem using linear programming techniques several possibilities often exist, and each results in a different mathematical formulation of the problem. Usually, advantages and disadvantages can be identified in any single formulation. In this paper we consider mixed integer...... linear programs and propose an approach based on Benders decomposition to exploit the advantages of two different formulations when solving a problem. We propose to apply Benders decomposition to a combined formulation,comprised of two separate formulations, augmented with linking constraints to ensure...

  6. Towards a methodology to formulate sustainable diets for livestock: accounting for environmental impact in diet formulation.

    Science.gov (United States)

    Mackenzie, S G; Leinonen, I; Ferguson, N; Kyriazakis, I

    2016-05-28

    The objective of this study was to develop a novel methodology that enables pig diets to be formulated explicitly for environmental impact objectives using a Life Cycle Assessment (LCA) approach. To achieve this, the following methodological issues had to be addressed: (1) account for environmental impacts caused by both ingredient choice and nutrient excretion, (2) formulate diets for multiple environmental impact objectives and (3) allow flexibility to identify the optimal nutritional composition for each environmental impact objective. An LCA model based on Canadian pig farms was integrated into a diet formulation tool to compare the use of different ingredients in Eastern and Western Canada. By allowing the feed energy content to vary, it was possible to identify the optimum energy density for different environmental impact objectives, while accounting for the expected effect of energy density on feed intake. A least-cost diet was compared with diets formulated to minimise the following objectives: non-renewable resource use, acidification potential, eutrophication potential, global warming potential and a combined environmental impact score (using these four categories). The resulting environmental impacts were compared using parallel Monte Carlo simulations to account for shared uncertainty. When optimising diets to minimise a single environmental impact category, reductions in the said category were observed in all cases. However, this was at the expense of increasing the impact in other categories and higher dietary costs. The methodology can identify nutritional strategies to minimise environmental impacts, such as increasing the nutritional density of the diets, compared with the least-cost formulation.

  7. A Comparison of Fick and Maxwell-Stefan Diffusion Formulations in PEMFC Cathode Gas Diffusion Layers

    OpenAIRE

    Lindstrom, Michael; Wetton, Brian

    2013-01-01

    This paper explores the mathematical formulations of Fick and Maxwell-Stefan diffusion in the context of polymer electrolyte membrane fuel cell cathode gas diffusion layers. Formulations of diffusion combined with mass-averaged Darcy flow are considered for three component gases. Fick formulations can be considered as approximations of Maxwell-Stefan in a certain sense. For this application, the formulations can be compared computationally in a simple, one dimensional setting. We observe that...

  8. Efficacy and safety of sublingual immunotherapy in children aged 6-24 months with rhinitis and bronchial asthma sensitized to house dust mites

    Directory of Open Access Journals (Sweden)

    Olimpio Rodríguez-Santos

    2015-11-01

    Full Text Available Serv The efficacy and safety of sublingual immunotherapy (SLIT was assessed in patients from Previsora Camagüey Clinic, who were diagnosed with allergic rhinitis and asthma. A retrospective case-control study was carried out. Cases and controls were selected in 62 children from 6 to 24 months of age: 34 children had used ITSL (cases; the other 28 children received only environmental prevention (controls. All children used medicines in the crisis stage. Quality of life questionnaires for rhinitis (RQLQm and asthma (AQLQm were applied. Medicine consumption and frequency of crises were analyzed. A subjective assessment of children health before and after the treatment was performed to relatives and physicians. Local and systemic reactions to SLIT were evaluated. An increase in the score of life quality questionnaires was detected (p=0.033. The medicine consumption was more reduced in cases than in controls (p=0.003. The frequency of respiratory symptomatology decreased (p=0.029. The score of subjective assessment was negative before treatment. After the treatment 85% of cases got 5 points, while the remaining 15% of cases obtained between 3 and 4 points. In the control group 55% of patients obtained 5 points, 10% of evaluated children between 3 and 4, and 5% between 0 and 2 points (p=0.011. Two mild adverse reactions to the SLIT were reported. Results showed that the sublingual immunotherapy with mites in children under 2 years old with rhinitis and asthma is effective and safe

  9. Multi-layered nanofibrous mucoadhesive films for buccal and sublingual administration of drug-delivery and vaccination nanoparticles - important step towards effective mucosal vaccines.

    Science.gov (United States)

    Mašek, Josef; Lubasová, Daniela; Lukáč, Róbert; Turánek-Knotigová, Pavlína; Kulich, Pavel; Plocková, Jana; Mašková, Eliška; Procházka, Lubomír; Koudelka, Štěpán; Sasithorn, Nongnut; Gombos, Jozsef; Bartheldyová, Eliška; Hubatka, František; Raška, Milan; Miller, Andrew D; Turánek, Jaroslav

    2017-03-10

    Nanofibre-based mucoadhesive films were invented for oromucosal administration of nanocarriers used for delivery of drugs and vaccines. The mucoadhesive film consists of an electrospun nanofibrous reservoir layer, a mucoadhesive film layer and a protective backing layer. The mucoadhesive layer is responsible for tight adhesion of the whole system to the oral mucosa after application. The electrospun nanofibrous reservoir layer is intended to act as a reservoir for polymeric and lipid-based nanoparticles, liposomes, virosomes, virus-like particles, dendrimers and the like, plus macromolecular drugs, antigens and/or allergens. The extremely large surface area of nanofibrous reservoir layers allows high levels of nanoparticle loading. Nanoparticles can either be reversibly adsorbed to the surface of nanofibres or they can be deposited in the pores between the nanofibres. After mucosal application, nanofibrous reservoir layers are intended to promote prolonged release of nanoparticles into the submucosal tissue. Reversible adsorption of model nanoparticles as well as sufficient mucoadhesive properties were demonstrated. This novel system appears appropriate for the use in oral mucosa, especially for sublingual and buccal tissues. To prove this concept, trans-/intramucosal and lymph-node delivery of PLGA-PEG nanoparticles was demonstrated in a porcine model. This system can mainly be used for sublingual immunization and the development of "printed vaccine technology". Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Once-daily sublingual allergen-specific immunotherapy improves quality of life in patients with grass pollen-induced allergic rhinoconjunctivitis: a double-blind, randomised study.

    Science.gov (United States)

    Rak, Sabina; Yang, William H; Pedersen, Martin R; Durham, Stephen R

    2007-03-01

    The effect of sublingual immunotherapy on quality of life (QoL) was examined in patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T Phleum pratense extract; GRAZAX or placebo. Treatment was initiated 8 weeks before the start of the grass pollen season and continued throughout. If symptoms were present, patients received loratadine or placebo rescue medication. There were three major findings: in patients using loratadine, grass allergen tablets provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with 75,000 SQ-T tablet than with placebo at first and second seasonal visit, respectively; in patients not using loratadine, grass allergen tablets improved QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ-T tablet at second seasonal visit; grass tablets (without loratadine) had a greater effect on QoL than loratadine alone. RQLQ score was 26% (p = 0.014) greater with 75,000 SQ-T tablets than loratadine at second seasonal visit. These data show that sublingual immunotherapy with grass allergen tablets improves QOL in allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater than rescue antihistamine alone.

  11. Effects of mometasone furoate/formoterol fumarate fixed-dose combination formulation on chronic obstructive pulmonary disease (COPD: results from a 52-week Phase III trial in subjects with moderate-to-very severe COPD

    Directory of Open Access Journals (Sweden)

    Doherty DE

    2012-02-01

    Full Text Available Dennis E Doherty1, Donald P Tashkin2, Edward Kerwin3, Barbara A Knorr4, Tulin Shekar4, Sibabrata Banerjee4, Heribert Staudinger41Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, 3Clinical Research Institute of Southern Oregon, Medford, OR, 4Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USARationale: The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD.Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1196, at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The trial’s co-primary endpoints were mean changes from baseline, as area under the curve (AUC, in forced expiratory volume (FEV1 over 0–12 hours (AUC0-12 h FEV1 with MF/F versus MF, and in morning (AM pre-dose (trough FEV1 with MF/F versus F after 13 weeks of treatment. Key secondary endpoints were the effects of MF/F on respiratory health status using the Saint George’s Respiratory Questionnaire (SGRQ, symptom-free nights, partly stable COPD at 26 weeks, and time to first COPD exacerbation.Results: The largest improvements in AUC0-12 h FEV1 were observed with MF/F 400/10 µg and MF/F 200/10 µg. Serial spirometry results demonstrated that bronchodilator effects with MF/F occurred rapidly (within 5 minutes, persisted for 12 hours after dosing, and were sustained over the 26-week treatment period. Similar findings were observed for AM pre-dose FEV1, for which effects were further investigated, excluding subjects whose AM FEV1 data were incorrectly collected after 2

  12. Dissolution Model Development: Formulation Effects and Filter Complications

    DEFF Research Database (Denmark)

    Berthelsen, Ragna; Holm, Rene; Jacobsen, Jette

    2016-01-01

    This study describes various complications related to sample preparation (filtration) during development of a dissolution method intended to discriminate among different fenofibrate immediate-release formulations. Several dissolution apparatus and sample preparation techniques were tested. The flow...... the mini paddle dissolution method demonstrates that sample preparation influenced the results. The investigations show that excipients from the formulations directly affected the drug–filter interaction, thereby affecting the dissolution profiles and the ability to predict the in vivo data....... With the tested drug–formulation combination, the best in vivo–in vitro correlation was found after filtration of the dissolution samples through 0.45-μm hydrophobic PTFE membrane filters....

  13. Abuse-Deterrent Opioid Formulations: Pharmacokinetic and Pharmacodynamic Considerations.

    Science.gov (United States)

    Walter, Carmen; Knothe, Claudia; Lötsch, Jörn

    2016-07-01

    Abuse-deterrent formulations (ADFs) are technologically sophisticated pharmaceutical formulations that impede manipulation and extraction of opioids and/or provoke unpleasant effects when they are taken in excessive quantity. This is implemented by creating physical barriers, inseparably combining the opioid with an opioid antagonist or adding aversive agents to the formulation. These pharmaceutical changes may potentially alter the pharmacokinetics and consequently the pharmacodynamics of the opioid. In this review, comparative evidence on pharmacokinetic differences between abuse-deterrent and classical formulations of the same opioids is summarized; furthermore, pharmacodynamic differences, with a focus on analgesia and abuse-related symptoms, are addressed. Most of the 12 studies comparing opioid pharmacokinetics have judged the physically intact ADF as being bioequivalent to the corresponding classical formulation. Pharmacokinetic differences have, however, been reported with physically manipulated ADFs and have ranged from moderate deviations from bioequivalence to complete changes in the pharmacokinetic profile (e.g. from a sustained-release formulation to a fast-release formulation). Pharmacodynamic effects were assessed in 14 comparative studies, which reported that intact ADFs usually provided clinically equivalent analgesia and clear advantages with respect to their addiction potential. However, withdrawal symptoms could be induced by the ADFs, although rarely and, in particular, when the ADFs had been physically altered. This evidence suggests that opioid ADFs are a working concept resulting in mostly minor pharmacokinetic and pharmacodynamic differences in comparison with classical formulations; however, they may deviate from this equivalence when physically altered.

  14. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  15. Novel Formulations for Antimicrobial Peptides

    Science.gov (United States)

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  16. Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs: a blind, randomized, placebo-controlled study.

    Science.gov (United States)

    Maina, E; Pelst, M; Hesta, M; Cox, E

    2017-01-18

    Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healthy dogs before testing it in food allergic dogs. Eight experimental healthy beagle dogs, never orally exposed to peanut, were randomized in two groups to receive SLIT with peanut or placebo for 4 months. Subjects were monitored daily for local and systemic adverse effects. Blood samples for complete blood count and serum biochemistry, and urine for urinalysis were collected and the dogs' body weight was recorded at day 0, 35 and 119 of the SLIT treatment. Sera for the determination of peanut-specific IgG and IgE were collected at day 0, 35, 49, 70, 91, 105 and 119. Intradermal tests were performed before (day 0) and after (day 119) the experiment. The content of each dispenser used to administer treatment or placebo was tested for sterility after usage. In order to assess the presence or absence of sensitization, dogs were challenged 6 months after the end of the study with 2000 μg of peanut extract daily for 7 to 14 days. All dogs completed the study. The treatment did not provoke either local or systemic side-effects. Peanut-specific IgG significantly increased in treatment group. Even though a significant increase in peanut-specific IgE was also seen, intradermal tests were negative in all dogs before and after the experiment, and the challenge test did not trigger any adverse reactions in the treated dogs, which shows the protocol did not cause sensitization to peanut, but nevertheless primed the immune system as indicated by the humoral immune response. All dispenser solutions

  17. Qualitative real-time analysis by nurses of sublingual microcirculation in intensive care unit: the MICRONURSE study.

    Science.gov (United States)

    Tanaka, Sébastien; Harrois, Anatole; Nicolaï, Camille; Flores, Mélanie; Hamada, Sophie; Vicaut, Eric; Duranteau, Jacques

    2015-11-06

    We aimed to determine i) the feasibility of nurses taking bedside measurements of microcirculatory parameters in real time in intensive care patients; and ii) whether such measurements would be comparable to those obtained by the classical delayed semi quantitative analysis made by a physician. This prospective observational study was conducted in a university hospital and was approved by our local Institutional Review Board (IRB 00006477). After ICU admission and study inclusion, a set of measurements of macrocirculatory and microcirculatory parameters was taken by the nurse in charge of the patient every 4 h within the first 12 h after admission and before and after every hemodynamic therapeutic intervention. Seventy-four sublingual microvascular measurements were performed with incident dark field illumination (IDF) microscopy in 20 mechanically ventilated patients hospitalized in the ICU. There were no significant differences between the microvascular flow index (MFI) taken in real time by the nurses and the delayed evaluation by the physician. In fact, the nurses' real-time measurement of MFI demonstrated good agreement with the physician's delayed measurement. The mean difference between the two MFIs was -0.15, SD = 0.28. The nurses' real-time MFI assessment showed 97 % sensitivity (95 % CI: 84-99 %) and 95 % specificity (95 % CI: 84-99 %) at detecting a MFI real-time TVD assessment showed 77 % sensitivity (95 % CI: 46-95 %) and 100 % specificity (95 % CI: 89-100 %) at detecting a TVD real-time qualitative bedside evaluation of MFI by nurses showed good agreement with the conventional delayed analysis by physicians. The bedside evaluations of MFI and TVD were highly sensitive and specific for detecting impaired microvascular flow and low capillary density. These results suggest that this real-time technique could become part of ICU nurse routine surveillance and be implemented in algorithms for hemodynamic resuscitation in future clinical trials and

  18. Sublingual immunization with adenovirus F protein-based vaccines stimulates protective immunity against botulinum neurotoxin A intoxication

    Science.gov (United States)

    Jun, SangMu; Clapp, Beata; Zlotkowska, Dagmara; Hoyt, Teri; Holderness, Kathryn; Maddaloni, Massimo

    2012-01-01

    Sublingual (s.l.) vaccination is an efficient way to induce elevated levels of systemic and mucosal immune responses. To mediate mucosal uptake, ovalbumin (OVA) was genetically fused to adenovirus 2 fiber protein (OVA-Ad2F) to assess whether s.l. immunization was as effective as an alternative route of vaccination. Ad2F-delivered vaccines were efficiently taken up by dendritic cells and migrated mostly to submaxillary gland lymph nodes, which could readily stimulate OVA-specific CD4+ T cells. OVA-Ad2F + cholera toxin (CT)-immunized mice elicited significantly higher OVA-specific serum IgG, IgA and mucosal IgA antibodies among the tested immunization groups. These were supported by elevated OVA-specific IgG and IgA antibody-forming cells. A mixed Th-cell response was induced as evident by the enhanced IL-4, IL-10, IFN-γ and TNF-α-specific cytokine-forming cells. To assess whether this approach can stimulate neutralizing antibodies, immunizations were performed with the protein encumbering the β-trefoil domain of C-terminus heavy chain (Hcβtre) from botulinum neurotoxin A (BoNT/A) as well as when fused to Ad2F. Hcβtre-Ad2F + CT-dosed mice showed the greatest serum IgG, IgA and mucosal IgA titers among the immunization groups. Hcβtre-Ad2F alone also induced elevated antibody production in contrast to Hcβtre alone. Plasma from Hcβtre + CT- and Hcβtre-Ad2F + CT-immunized groups neutralized BoNT/A and protected mice from BoNT/A intoxication. Most importantly, Hcβtre-Ad2F + CT-immunized mice were protected from BoNT/A intoxication relative to Hcβtre + CT-immunized mice, which only showed ∼60% protection. This study shows that s.l. immunization with Ad2F-based vaccines is effective in conferring protective immunity. PMID:22207133

  19. Formulation Optimization of Arecoline Patches

    Directory of Open Access Journals (Sweden)

    Pao-Chu Wu

    2014-01-01

    Full Text Available The response surface methodology (RSM including polynomial equations has been used to design an optimal patch formulation with appropriate adhesion and flux. The patch formulations were composed of different polymers, including Eudragit RS 100 (ERS, Eudragit RL 100 (ERL and polyvinylpyrrolidone K30 (PVP, plasticizers (PEG 400, and drug. In addition, using terpenes as enhancers could increase the flux of the drug. Menthol showed the highest enhancement effect on the flux of arecoline.

  20. Inhaled dry powder formulations for treating tuberculosis.

    Science.gov (United States)

    Das, Shyamal; Tucker, Ian; Stewart, Peter

    2015-01-01

    Tuberculosis is the second leading cause of death from infectious diseases. Although antitubercular drugs have been traditionally administered orally, there is a growing interest in delivering drugs via the pulmonary route using nebulisers or dry powder inhalers. Drugs in dry powder inhalers (DPI) are stable and DPI are user-friendly compared to nebulisation which is time consuming, inconvenient and inefficient and requires special equipment. For tuberculosis treatment, drugs should target alveolar macrophages that harbour microorganisms and/or maintain high drug concentration at the infection site in the lung. Drug particles include micro-particles or nanoparticles. Powders can be engineered by micronisation, crystallisation, spray drying, freeze drying and particle coating approaches. The formulation may contain single or combination drugs. This paper will provide an update on current status of TB, its pathogenesis, current treatment strategies, shortcomings of current oral or parenteral delivery strategies, pulmonary delivery devices, advantages of pulmonary delivery of powder formulations, formulation approaches and pharmacokinetic studies of pulmonary delivery of powders for inhalation.

  1. Texturing formulations for uranium skin decontamination.

    Science.gov (United States)

    Belhomme-Henry, Corinne; Phan, Guillaume; Huang, Nicolas; Bouvier, Céline; Rebière, François; Agarande, Michelle; Fattal, Elias

    2014-09-01

    Since no specific treatment exists in case of cutaneous contamination by radionuclides such as uranium, a nanoemulsion comprising calixarene molecules, known for their good chelation properties, was previously designed. However, this fluid topical form may be not suitable for optimal application on the skin or wounds. To develop a texturing pharmaceutical form for the treatment of wounded skins contaminated by uranium. The formulations consisted in oil-in-water (O/W) nanoemulsions, loaded with calixarene molecules. The external phase of the initial liquid nanoemulsion was modified with a combination of thermosensitive gelifying polymers: Poloxamer and HydroxyPropylMethylcellulose (HPMC) or methylcellulose (MC). These new formulations were characterized then tested by ex vivo experiments on Franz cells to prevent uranyl ions diffusion through excoriated pig ear skin explants. Despite strong changes in rheological properties, the physico-chemical characteristics of the new nanoemulsions, such as the size and the zeta potential as well as macroscopic aspect were preserved. In addition, on wounded skin, diffusion of uranyl ions, measured by ICP-MS, was limited to less than 5% for both HPMC and MC nanoemulsions. These results demonstrated that a hybrid formulation of nanoemulsion in hydrogel is efficient to treat uranium skin contamination.

  2. Midazolam-sirupus, formulation and pharmacodynamic efficacy

    Directory of Open Access Journals (Sweden)

    K. Goracinova

    2002-04-01

    Full Text Available Due to its pharmacokinetic and pharmacodynamic properties (sedation, amnesia and relief of anxiety Midazolam has become a comm only used agent for conscious sedation of children before diagnostic or therapeutic procedure or before induction of anesthesia. Con sidering the advantage of oral administration to avoid the additional trauma of starting an IV in the child, and the fact that there is no ad equate dosage form (Midazolam - Syrupus on the drug market in our country, the aim of the presented work was to formulate syrupus using syrupus b ase/aqueous solution of viscosity enhancer - HPMC, in combination with suitable sweetener, flavor, and preservatives, and to evaluate its q uality and stability. The pharmacodynamic efficacy/sedative effect of Midazolam HCl - Syrupus formulation was evaluated in 33 pediatric patients comp aring this with the efficacy of intramuscularly administered Midazolam HCl (35 pediatric patients in accordance with the Ramsay scale for analgosedation. The formulation manifested good quality in respect to physical properties, physico-chemical parameters (pH value, relative dens ity, drug content, ingredients content antimicrobial efficacy and microbiological quality according to Ph Eur 3. In the conditions chara cteristic of the second (II climate zone, the dosage form was stable for four months. The sedative effect of orally administered Midazolam was manifested in a period necessary for surgical premedication (30 - 45 min. The majority of patients (71% entered the second phase on the Ramsa y scale, when Midazolam was administered in a dose of 0.40 mg/kg.

  3. Tactile friction of topical formulations.

    Science.gov (United States)

    Skedung, L; Buraczewska-Norin, I; Dawood, N; Rutland, M W; Ringstad, L

    2016-02-01

    The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Efeitos de misoprostol sublingual pré-operatório no tônus uterino durante anestesia com isoflurano para cesariana

    Directory of Open Access Journals (Sweden)

    Mohamed R. El Tahan

    2012-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Misoprostol reduz o sangramento uterino após o parto cesáreo sem efeitos prejudiciais para a mãe ou o bebê. Nosso objetivo foi avaliar os efeitos de misoprostol pré-operatório no sangramento materno e no tônus uterino e a necessidade de ocitocina após cesariana sob anestesia com isoflurano. MÉTODOS: Depois da aprovação pelo Comitê de Ética, 366 pacientes programadas para cesariana eletiva foram randomicamente designadas para receber 400 µg de misoprostol sublingual (n = 179 ou um comprimido de placebo (n = 187 após intubação. A anestesia foi mantida com CAM de isoflurano a 0,5-0,7 e óxido nitroso. Todas as pacientes receberam infusão de ocitocina (10 UI após expulsão da placenta. A estimativa de perda sanguínea, do tônus uterino, da necessidade de ocitocina complementar, da contagem de hematócrito, dos escores de Apgar no 1º e aos 5 minutos e os efeitos adversos foram registrados. RESULTADOS: Após a indução, as pacientes que receberam misoprostol sublingual tiveram perda sanguínea perioperatória (202 ± 383,1 vs 708 ± 204,3 mL, p < 0,001, necessidade de ocitocina (p < 0,001, níveis mais elevados de hematócrito (p < 0,001 e tônus uterino (p < 0,02 menos significativos. A incidência de tremores foi maior no grupo misoprostol (p = 0,04. Não houve diferenças entre os dois grupos quanto aos índices de Apgar, náusea e vômito, distúrbios gastrointestinais e febre. CONCLUSÃO: A administração pré-operatória de misoprostol sublingual (400 µg é segura e eficaz para atenuar o sangramento materno e o efeito no tônus uterino da anestesia com isoflurano em parto cesário.

  5. Fentanyl Sublingual Tablets Versus Subcutaneous Morphine for the Management of Severe Cancer Pain Episodes in Patients Receiving Opioid Treatment: A Double-Blind, Randomized, Noninferiority Trial.

    Science.gov (United States)

    Zecca, Ernesto; Brunelli, Cinzia; Centurioni, Fabio; Manzoni, Andrea; Pigni, Alessandra; Caraceni, Augusto

    2017-03-01

    Purpose Fentanyl sublingual tablets (FST) are a potentially useful alternative to parenteral opioids such as subcutaneous morphine (SCM) to treat severe cancer pain episodes. No direct comparison between FST and SCM is available. The aim of this study was to test noninferiority of FST versus SCM during the first 30 min postadministration. Methods Patients receiving stable opioid therapy and experiencing a severe pain episode were randomly assigned to either 100 µg FST or 5 mg SCM in a double-blind, double-dummy trial. Average pain intensity (PI) assessed on a 0 to 10 numerical rating scale at 10, 20, and 30 min postadministration was the main end point. Analysis of covariance, adjusted by baseline PI, was the main analysis. The noninferiority margin (NIm) for the between-group difference was set at -0.6, that is, equal to one third of the minimum clinically important PI difference of two points. Results A total of 114 patients were randomly assigned to either FST (n = 58) or SCM (n = 56). One patient (in the FST group) withdrew consent before drug administration and was excluded from analysis. Baseline mean PIs were 7.5 in both groups; mean average PIs assessed at 10, 20, and 30 min postadministration were 5.0 and 4.5 for FST and SCM, respectively, with the 95% CI of the between-group difference including the NIm (-0.49; 95% CI, -1.10 to 0.09). Patients taking FST received a second drug dose after 30 min more frequently than did patients taking SCM (51% v 37%, respectively; risk difference, -13%; 95% CI, -30% to 3%). Both treatments were well tolerated, with average follow-up adverse event scores below the response of "A Little." Ninety-three percent of patients preferred the sublingual administration. Conclusion This trial did not show noninferiority of FST versus SCM within the chosen NIm. Both treatments were safe, and patients preferred the sublingual route of administration. FST provides analgesia with modest to moderate increased risk of lower efficacy

  6. Formulation design of fast disintegrating tablets using disintegrant blends.

    Science.gov (United States)

    Shirsand, S B; Suresh, Sarasija; Swamy, P V; Para, M S; Nagendra Kumar, D

    2010-01-01

    In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by direct compression method. In this method, crospovidone (up to 3% w/w) and croscarmellose sodium (up to 5% w/w) in combination were used as superdisintegrants. Since disintegrants complement each other, accelerating the disintegration process when used together. Estimation of prochlorperazine maleate in the prepared tablet formulations was carried out by extracting the drug with methanol and measuring the absorbance at 254.5nm. The prepared formulations were further evaluated for hardness, friability, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 12 s), one promising formulation was tested for in vitro drug release pattern in phosphate buffer pH 6.8 and short-term stability (at 40 degrees /70% RH for 3 mo), drug-excipient interaction (IR spectroscopy) were studied. Among the formulations tested, formulation DCPC(4) containing 5% w/w of croscarmellose sodium and 3% w/w of crospovidone as superdisintegrant emerged as the overall best (t(50%) 7.0 min) based on drug release characteristics in pH 6.8 phosphate buffer compared to commercial conventional tablet formulation (t(50%) 17.4 min). Short-term stability studies on the promising formulation indicated that there were no significant changes in drug content and in vitro dispersion time (p<0.05).

  7. Alternative formulations, delivery methods, and administration options for psychotropic medications in elderly patients with behavioral and psychological symptoms of dementia.

    Science.gov (United States)

    Muramatsu, Russ S; Litzinger, Mark H J; Fisher, Ed; Takeshita, Junji

    2010-04-01

    The purpose of this paper was to review alternative formulations, delivery methods, and administration options for psychotropic medications in elderly patients with behavioral and psychological symptoms of dementia (BPSD). A MEDLINE search was conducted initially in December 2008 and was updated in September 2009, including the search terms pharmacologic treatment and dementia, behavioral and psychological symptoms of dementia, alternative psychotropic medication formulations, alternative dosing methods of medication, drug delivery options, antidepressants and dementia, anxiolytics and dementia, antipsychotics and dementia, mood stabilizers and dementia, cognitive enhancers and dementia, medications and enteral feeding tubes, and hiding medication. Studies were limited to English-language articles dated from 1950 to 2009. Additional relevant articles were obtained by reviewing the references in the initial articles. Drug Facts and Comparisons 4.0 Online, Lexi-Comp Online, and Lexi-Drugs Online were used to obtain additional information. Targeted patients were elderly individuals with BPSD who were considered difficult to treat because they were unable to swallow, were refusing medications, or were not able to eat or drink per physician order. In addition to the standard capsule or tablet given orally, a variety of formulations and delivery methods for psychotropic medications are available. Options include short- and long-acting intramuscular, intravenous, liquid, orally disintegrating, transdermal patch, sublingual, and rectal forms. Additionally, all formulations can be further altered in substance, delivery, or both. For example, tablets may be crushed and capsules opened; this changes their formulation and allows the option of mixing with food or liquids to be taken by mouth or through a tube. Caution must be used, however; in certain cases, alteration of the original form or the intended delivery method is contraindicated. In addition, many alternative

  8. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings.

    Science.gov (United States)

    Li, Jie; Li, Xin; Ren, Yu-Shan; Lv, Yuan-Yuan; Zhang, Jun-Sheng; Xu, Xiao-Li; Wang, Xian-Zhen; Yao, Jing-Chun; Zhang, Gui-Min; Liu, Zhong

    2017-01-01

    Although arctigenin (AG) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i.v), hypodermic injection (i.h), and sublingual (s.l) administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate 100%), and a strong elimination ability (t1/2 beagle dog (25.9 ± 3.24%) > rat (15.7 ± 9%) > monkey (3.69 ± 0.12%). This systematic investigation of pharmacokinetic profiles of arctigenin (AG) in vivo and in vitro is worthy of further exploration.

  9. Comparative analysis of the oral mucosae from rodents and non-rodents: Application to the nonclinical evaluation of sublingual immunotherapy products.

    Directory of Open Access Journals (Sweden)

    Catherine Thirion-Delalande

    Full Text Available A comparative characterization of the oral mucosa in various animals is needed to identify the best animal model(s for nonclinical evaluation of sublingual immunotherapy products. With this aim, we studied the histological characteristics and immune cell infiltrates of oral mucosae from common animal species.Three oral regions (i.e. ventral surface of the tongue, mouth floor and cheek obtained from eight animal species, including rodents (i.e. mice, rats, hamsters, guinea pigs and non-rodents (i.e. rabbits, dogs, minipigs and monkeys were characterized by histology and immunohistology in comparison with a human tongue.Rodents exhibit a thin keratinized epithelium with low epithelial extensions, whereas non-rodents, most particularly minipigs and monkeys, display a non-keratinized epithelium with larger rete ridges, similarly to humans. Glycogen-rich cells in the superficial epithelial layers are observed in samples from both minipigs, monkeys and humans. Comparable immune subpopulations detected in the 3 oral regions from rodent and non-rodent species include MHC-II+ antigen presenting cells, mostly CD163+ macrophages, located in the lamina propria (LP and muscle tissue in the vicinity of resident CD3+CD4+ T cells. Limited numbers of mast cells are also detected in the LP and muscle tissue from all species.The oral mucosae of minipigs and monkeys are closest to that of humans, and the immune networks are quite similar between all rodents and non-rodents. Taking into account the ethical and logistical difficulties of performing research in the latter species, rodents and especially mice, should preferentially be used for pharmacodynamics/efficacy studies. Our data also support the use of minipigs to perform biodistribution and safety studies of sublingual immunotherapy products.

  10. A Cost-Minimisation Analysis Comparing Sublingual Immunotherapy to Subcutaneous Immunotherapy for the Treatment of House Dust Mite Allergy in a Swedish Setting.

    Science.gov (United States)

    Björstad, Åse; Cardell, Lars-Olaf; Hahn-Pedersen, Julie; Svärd, Mikael

    2017-06-01

    In Sweden, approximately 6% of children and 10% of adults suffer from house dust mite (HDM) allergy with symptoms of allergic rhinitis and allergic asthma. Treatment is aimed at reducing HDM exposure and to control the symptoms of allergic rhinitis and allergic asthma by symptom-relieving pharmacotherapy. This pharmacotherapy is often effective, but some patients remain inadequately controlled. For these patients, allergy immunotherapy (AIT, subcutaneous or sublingual) with repeated administration of HDM allergen should be considered. The objective of this study was to compare the costs for sublingual AIT (SLIT; SQ® SLIT-tablet) to the costs for subcutaneous AIT (SCIT; SQ® SCIT) for the treatment of HDM allergy in a cost-minimisation analysis (CMA). The CMA included resources (and costs) for treatment, healthcare visits, travelling and lost productivity. Resource use based on Swedish clinical treatment practice and costs were obtained from medical price lists. Analyses were conducted from the societal, as well as healthcare perspective, by use of a time horizon of 3 years. The results show that SQ® SLIT-tablet is a cost-saving treatment as compared to SQ® SCIT for the treatment of HDM allergy (€6800 over 3 years). The results are mainly driven by the cost of healthcare visits and the frequency of SCIT administrations. In conclusion, cost-savings of €6800 over 3 years are expected from treating HDM allergy with SQ® SLIT-tablet as compared to SQ® SCIT, including costs for treatment, healthcare visits, travelling and lost productivity. The reduced number of healthcare visits compensates for higher medication costs.

  11. Objective approach for fending off the sublingual immunotherapy placebo effect in subjects with pollenosis: double-blinded, placebo-controlled trial.

    Science.gov (United States)

    Kralimarkova, Tanya Z; Popov, Todor A; Staevska, Maria; Mincheva, Roxana; Lazarova, Cvetelina; Racheva, Rumyana; Mustakov, Tihomir B; Filipova, Violina; Koleva, Margarita; Bacheva, Kalina; Dimitrov, Vasil D

    2014-07-01

    Symptom scoring for the assessment of allergen immunotherapy is associated with a substantial placebo effect. To assess the ability of exhaled breath temperature (EBT), a putative marker of airway inflammation, to evaluate objectively the efficacy of grass pollen sublingual immunotherapy in a proof-of-concept study. This was a double-blinded, placebo-controlled clinical trial in 56 subjects (mean ± SD 30 ± 12 years old, 33 men) sensitized to grass pollen. The objective measurements were EBT, spirometry, and periostin and high-sensitivity C-reactive protein in blood. Overall discomfort scored on a visual analog scale was used as a proxy for subjective symptoms. Evaluations were performed before, during, and after the grass pollen season. Fifty-one subjects (25 and 26 in the active treatment and placebo groups, respectively) were assessed before and during the pollen season. The mean pre- vs in-season increase in EBT was significantly smaller (by 59.1%) in the active treatment than in the placebo group (P = .030). Of the other objective markers, only the blood periostin level increased significantly during the pollen season (P = .047), but without intergroup differences. Subjectively, the mean pre- vs in-season increase in the visual analog scale score was 32.3% smaller in the active treatment than in the placebo group, although this difference did not reach statistical significance (P = .116). These results suggest that the efficacy of grass pollen sublingual immunotherapy can be assessed by EBT, a putative quantitative measurement of airway inflammation, which is superior in its power to discriminate between active and placebo treatment than a subjective assessment of symptoms assessed on a visual analog scale. clinicaltrials.gov Identifier: NCT01785394. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Continuous Perioperative Sublingual Buprenorphine.

    Science.gov (United States)

    Silva, Marcelina Jasmine; Rubinstein, Andrea

    2016-12-01

    Buprenorphine, a semisynthetic thebaine derivative, is a unique opioid, as it has activity at multiple receptors, including mu (partial agonist), kappa (antagonist), OLR-1 (agonist), and delta (antagonist). Because buprenorphine's pharmacology is relatively complex, misconceptions about its actions are common. Most other opioids act solely or predominately as full mu receptor agonists. Common practice at many institutions calls for the cessation of regular buprenorphine use 48-72 hours prior to surgery. This practice is based on three foundational theories that have come from scant data about the properties of buprenorphine: (1) that buprenorphine is only a partial mu agonist and therefore is not a potent analgesic; (2) because buprenorphine has a ceiling effect on respiratory depression, it also has a ceiling effect on analgesia; and (3) that buprenorphine acts as a "blockade" to the analgesic effects of other opiates when coadministered due to its strong binding affinity. However, several recent studies have called this practice into question. At our institution, we continue buprenorphine perioperatively, whenever possible, in order to provide superior pain control, discourage potentially problematic use and the more dangerous side effects of full mu agonist opiates, and avoid putting recovery at risk for those with opiate dependency issues. We present a unique case comparing two different outcomes for the same surgical course performed at two different times on the same chronic pain patient. These differences may be attributable to the variable of buprenorphine being present for one perioperative course and not the other. Pain control was easier to achieve, and functional recovery was greater when buprenorphine was maintained throughout the perioperative period when compared with using a full mu agonist opioid for chronic pain preoperatively. This is an outcome that much of the literature heretofore suggests would be unlikely. We review some aspects of buprenorphine's unique pharmacology that may explain why remaining on buprenorphine perioperatively may be preferable, which contradicts many practice guidelines.

  13. On Hamiltonian formulation of cosmologies

    Indian Academy of Sciences (India)

    matter era for some cosmological models. It is argued that these solutions appear to hint at their possible relevance in the early phase of cosmological evolution. Keywords. Hamiltonian formulation; some cosmologies. PACS No. 98.80. Hw. It has been shown by Novelloet al [1,2] that it is possible to study perturbations in the ...

  14. Hamiltonian formulation of the supermembrane

    NARCIS (Netherlands)

    Bergshoeff, E.; Sezgin, E.; Tanii, Y.

    1988-01-01

    The hamiltonian formulation of the supermembrane theory in eleven dimensions is given. The covariant split of the first and second class constraints is exhibited, and their Dirac brackets are computed. Gauge conditions are imposed in such a way that the reparametrizations of the membrane with

  15. Formulation and Permeation Kinetic Studies of Flurbiprofen Gel

    African Journals Online (AJOL)

    microcapsules, nanocapsules, niosomes, liposomes, emulsion-based systems, and use of different vehicle-chemical enhancer combina- tions (6-8). Chemical ... formulation design is given in Table 2. Table 2: .... Table 3: Factor combinations as per (a) chosen experimental design and (b) translation of coded levels in actual.

  16. Formulation Optimization and In-vitro Evaluation of Oral Floating ...

    African Journals Online (AJOL)

    Calcium carbonate was used as gasgenerating agent. After setting the levels by preliminary trials, nine tablet formulations (F1 - F9) were prepared by wet granulation method using Design Expert Software® - suggested combinations of polymers. The concentrations of HPMC K100M (X1) and xanthan gum (X2) were chosen ...

  17. Technical Status Report: Preliminary Glass Formulation Report for INEEL HAW

    Energy Technology Data Exchange (ETDEWEB)

    Peeler, D. [Westinghouse Savannah River Company, AIKEN, SC (United States); Reamer, I.; Vienna, J.; Crum, J.A.

    1998-03-01

    This study was performed by a team comprising experts in glass chemistry, glass technology, and statistics at both SRTC and PNNL. This joint effort combined the strengths of each discipline and site to quickly develop a glass formulation for specific INEEL HAW.

  18. Cleaning UF membranes with simple and formulated solutions

    NARCIS (Netherlands)

    Levitsky, I.; Duek, A.; Naim, R.; Arkhangelsky, E.; Gitis, V.

    2012-01-01

    The ultrafiltration membranes fouled by proteins are typically cleaned by consecutive soaking in alkali, surfactant and oxidizing solutions. We combined all three chemicals into a formulated cleaning agent and examined its efficiency to restore the water flux without damaging the membrane or

  19. Formulation and In vitro Evaluation of Natural Gum-Based ...

    African Journals Online (AJOL)

    microbeads ranged from 35.3 to 79.8 % and dissolution times, t15 and t80 increased with increase in the concentration of the natural gums present in the blends. Controlled release was obtained for over 4 h and the release was found to be by a combination of diffusion and erosion mechanisms from spherical formulations.

  20. Development of sludge based stable aqueous Bacillus thuringiensis formulations.

    Science.gov (United States)

    Brar, S K; Verma, M; Tyagi, R D; Valéro, J R; Surampalli, R Y; Banerji, S K

    2004-01-01

    This study focuses on development of aqueous flowable (suspension) formulations for Bacillus thuringiensis (Bt) based biopesticides from wastewater sludge. Different inerts like sorbitol, sodium monophosphate, sodium metabisulphite, sorbic acid, propionic acid, Tween-80, Triton X-100 and glycerol were tested for formulations. Five different formulations for non-hydrolyzed (NH) secondary sludges were tried and the best combination selected on the basis of various physical parameters like viscosity, particle size, suspendibility, entomotoxicity, and microbiological purity tests. F5 formulations (for secondary sludge) comprising sorbitol, sodium monophosphate and sodium metabisulphite gave better physical and biological characteristics with a small effect on entomotoxicity and spore concentration after 120 days at pH 6, 6.5 and temperatures 40 and 50 degrees C and viscosity change at 40 and 50 degrees C. The formulations were more stable at pH 4.0 to 5.0 and temperatures 4 to 30 degrees C whereas at pH 6.0 and 6.5 and temperatures 40 and 50 degrees C, there was degeneration of the product. Lower proteolytic activity and physical factors like ionic strength and surface group changes at pH 6 and 6.5 were responsible for the instability of the formulation.

  1. Optimization of formulation variables of benzocaine liposomes using experimental design.

    Science.gov (United States)

    Mura, Paola; Capasso, Gaetano; Maestrelli, Francesca; Furlanetto, Sandra

    2008-01-01

    This study aimed to optimize, by means of an experimental design multivariate strategy, a liposomal formulation for topical delivery of the local anaesthetic agent benzocaine. The formulation variables for the vesicle lipid phase uses potassium glycyrrhizinate (KG) as an alternative to cholesterol and the addition of a cationic (stearylamine) or anionic (dicethylphosphate) surfactant (qualitative factors); the percents of ethanol and the total volume of the hydration phase (quantitative factors) were the variables for the hydrophilic phase. The combined influence of these factors on the considered responses (encapsulation efficiency (EE%) and percent drug permeated at 180 min (P%)) was evaluated by means of a D-optimal design strategy. Graphic analysis of the effects indicated that maximization of the selected responses requested opposite levels of the considered factors: For example, KG and stearylamine were better for increasing EE%, and cholesterol and dicethylphosphate for increasing P%. In the second step, the Doehlert design, applied for the response-surface study of the quantitative factors, pointed out a negative interaction between percent ethanol and volume of the hydration phase and allowed prediction of the best formulation for maximizing drug permeation rate. Experimental P% data of the optimized formulation were inside the confidence interval (P < 0.05) calculated around the predicted value of the response. This proved the suitability of the proposed approach for optimizing the composition of liposomal formulations and predicting the effects of formulation variables on the considered experimental response. Moreover, the optimized formulation enabled a significant improvement (P < 0.05) of the drug anaesthetic effect with respect to the starting reference liposomal formulation, thus demonstrating its actually better therapeutic effectiveness.

  2. Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

    OpenAIRE

    Xia, Binfeng; Yang, Zhen; Zhou, Haiying; Lukacova, Viera; Zhu, Wei; Milewski, Mikolaj; Kesisoglou, Filippos

    2015-01-01

    Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms. The purpose of this work was to develop and evaluate a novel, physiologically based oral cavity model for projection and mechanistic analysis of the clinical pharmacokinetics of intraoral formulations. The GastroPlus™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentr...

  3. Realism Versus Neoliberalism: A Formulation

    OpenAIRE

    Niou, Emerson M. S.; Ordeshook, Peter C.

    1989-01-01

    Although the debate between realism and neoliberalism offers deep insights and raises fundamental questions into the nature of international systems, it also offers the confusion that accompanies imprecisely formulated concepts and an imperfect application of subsidiary ideas. Using a noncooperative extensive-form game to model anarchic international systems, this essay seeks to resolve that debate by restating it in a more explicit and deductive context. Arguing that collective security corr...

  4. A Newly Developed Sublingual Tonometric Method for the Evaluation of Tissue Perfusion and Its Validation In Vitro and in Healthy Persons In Vivo and the Results of the Measurements in COPD Patients

    Science.gov (United States)

    2014-01-01

    Introduction. Since its first publication in the medical literature, an extremely large number of references have demonstrated that the tonometric measurement of tissue perfusion is a reliable indicator of the actual condition of critically ill patients. Later a new method was developed by the introduction of sublingual tonometry for the determination of tissue perfusion. In comparison with gastric tonometry, the new method was simpler and could even be used in awake patients. Unfortunately, at present, because of severe failures of manufacturing, the device is withdrawn from commerce. Materials and Methods. In this study, we present a new method using a newly developed tool for the PslCO2 measurement in sublingual tonometry as well as the data for its validation in vitro and in vivo and the results of 25 volunteers and 54 COPD patients belonging to different GOLD groups at their hospitalization due to the acute exacerbation of the disease but already in a stable condition at the time of the examination. Results and Conclusion. The results of the performed examinations showed that the method is suitable for monitoring the actual condition of the patients by mucosal perfusion tonometry in the sublingual region. PMID:25580290

  5. A Newly Developed Sublingual Tonometric Method for the Evaluation of Tissue Perfusion and Its Validation In Vitro and in Healthy Persons In Vivo and the Results of the Measurements in COPD Patients

    Directory of Open Access Journals (Sweden)

    Zoltán Rózsavölgyi

    2014-01-01

    Full Text Available Introduction. Since its first publication in the medical literature, an extremely large number of references have demonstrated that the tonometric measurement of tissue perfusion is a reliable indicator of the actual condition of critically ill patients. Later a new method was developed by the introduction of sublingual tonometry for the determination of tissue perfusion. In comparison with gastric tonometry, the new method was simpler and could even be used in awake patients. Unfortunately, at present, because of severe failures of manufacturing, the device is withdrawn from commerce. Materials and Methods. In this study, we present a new method using a newly developed tool for the PslCO2 measurement in sublingual tonometry as well as the data for its validation in vitro and in vivo and the results of 25 volunteers and 54 COPD patients belonging to different GOLD groups at their hospitalization due to the acute exacerbation of the disease but already in a stable condition at the time of the examination. Results and Conclusion. The results of the performed examinations showed that the method is suitable for monitoring the actual condition of the patients by mucosal perfusion tonometry in the sublingual region.

  6. Produtividade do Sorgo granífero cv. sacarino e qualidade de produtos formulados isoladamente ou combinados ao caldo de cana-de-açúcar Yield of Sorghum bicolor cv. sacarino and quality of products formulated isolated or combined with sugar cane juice

    Directory of Open Access Journals (Sweden)

    Cassiara Camelo de Souza

    2005-09-01

    Full Text Available Este trabalho teve como objetivo avaliar o comportamento produtivo do Sorgo granífero (Sorghum bicolor L variedade IPA- 467, mediante condições de irrigação e adubação, bem como, a caracterização físico-química da farinha de diferentes tipos de grãos e de rapadura obtida a partir de combinações de caldo de sorgo (CS x caldo de cana (CC. O experimento resultou em uma produção de biomassa, sementes, colmo, caldo, melaço fino e melaço grosso, respectivamente, de: 64t/ha; 3,5t/ha; 46t/ha; 700L/t de colmo; 140L/t de colmo e 90L/t de colmo. A farinha obtida a partir de grãos de sorgo apresenta teor de açúcares totais inferior aos da farinha de trigo. As rapaduras em que o caldo de sorgo foi adicionado nas proporções de 10 e 20%, em associação com o caldo-de-cana, obtiveram maior nível de aceitação, quando comparada à rapadura obtida a partir de 100% de caldo de cana-de-açúcar. A aceitação de rapaduras formuladas a partir 30% de caldo sorgo e 70% de caldo de cana não diferiu de rapaduras obtidas de 100% de caldo de cana.The objective of this work was to evaluate the yield of Sorghum bicolor var. IPA-467, under irrigation and fertilizer conditions and the physical-chemical characterization of grain flours and 'rapadura' obtained from combinations of sorghum stem juice (SJ x sugar cane juice (CJ. The experiment resulted im biomass production, seeds, stem, juice, thick sugarcane syrup, respectively of 64t/ha; 3,5t/ha, 46t/ha, 700L/t of stem, 140L/t of stem and 90L/t of stem. The total sugars of sorghum grain flour were lower than results reported for wheat flour. 'Rapaduras' in which sorghum juice was used at 10 and 20, in combination of sugar cane juice, had higher acceptance scores, as compared with 'rapadura' obtaned from 100% sugar cane juice. The acceptance of 'rapaduras' formulated from 30% SJ x 70% CJ did not differ from those obtained from 100% CJ.

  7. A formulation consideration for orthogonal collocation procedures. [for parabolic differential equations simulating fluid-mechanical processes

    Science.gov (United States)

    Lashmet, P. K.; Woodrow, P. T.

    1975-01-01

    Numerical instabilities often arise in the use of high-ordered collocation approximations for numerically solving parabolic partial differential equations. These problems may be reduced by formulations involving evaluation of collocation polynomials rather than combination of the polynomials into a power series. As an illustration, two formulations using shifted Legendre polynomials of order 26 and less are compared.

  8. An algebraic approach to symmetric extended formulations

    OpenAIRE

    Braun, Gábor; Pokutta, Sebastian

    2012-01-01

    Extended formulations are an important tool to obtain small (even compact) formulations of polytopes by representing them as projections of higher dimensional ones. It is an important question whether a polytope admits a small extended formulation, i.e., one involving only a polynomial number of inequalities in its dimension. For the case of symmetric extended formulations (i.e., preserving the symmetries of the polytope) Yannakakis established a powerful technique to derive lower bounds and ...

  9. Perfume formulation: words and chats.

    Science.gov (United States)

    Ellena, Céline

    2008-06-01

    What does it mean to create fragrances with materials from chemistry and/or from nature? How are they used to display their characteristic differences, their own personality? Is it easier to create with synthetic raw materials or with essential oils? This review explains why a perfume formulation corresponds in fact to a conversation, an interplay between synthetic and natural perfumery materials. A synthetic raw material carries a single information, and usually is very linear. Its smell is uniform, clear, and faithful. Natural raw materials, on the contrary, provide a strong, complex and generous image. While a synthetic material can be seen as a single word, a natural one such as rose oil could be compared to chatting: cold, warm, sticky, heavy, transparent, pepper, green, metallic, smooth, watery, fruity... full of information. Yet, if a very small amount of the natural material is used, nothing happens, the fragrance will not change. However, if a large amount is used, the rose oil will swallow up everything else. The fragrance will smell of nothing else except rose! To formulate a perfume is not to create a culinary recipe, with only dosing the ingredients in well-balanced amounts. To formulate rather means to flexibly knit materials together with a lively stitch, meeting or repelling each other, building a pleasant form, which is neither fixed, nor solid, nor rigid. A fragrance has an overall structure, which ranges from a clear sound, made up of stable, unique, and linear items, to a background chat, comfortable and reassuring. But that does, of course, not mean that there is only one way of creating a fragrance!

  10. Formulation of soy oil products

    Directory of Open Access Journals (Sweden)

    Woerfel, John B.

    1995-12-01

    Full Text Available The paper comments different formulations of soy oil products such as salad and cooking oils, margarine, shortenings, commercial shortenings, frying shortenings, and fluid shortenings. Hydrogenation and its influence on final products is also included.

    El trabajo presenta diferentes formulaciones a base de aceite de soja tales como aceites para ensalada y cocinado, margarina, grasas sólidas (shortenings, grasas sólidas comerciales, grasas sólidas para frituras y grasas fluidas. Hace también referencia al proceso de hidrogenación y a sus efectos en los productos finales.

  11. ANTI-RHEUMATIC FORMULATIONS FROM AYURVEDA

    Science.gov (United States)

    Raut, A. A.; Joshi, A. D.; Antarkar, D. S.; Joshi, V. R.; Vaidya, A. B.

    1991-01-01

    Rheumatic disorders like Amavata, Sandhivata and Vatarakta are elaborately described in ayurvedic literature. Preliminary survey of literature shows that about 247 formulations are recommended for these rheumatic disorders. These formulations generally include guggulu compounds, compounds of plant powders, decoctions, medicated ghees, oils, electuaries etc. Therapeutic potential of ayurvedic concepts and a brief review of Ayurvedic formulations are also discussed. PMID:22556565

  12. Performance Evaluation of Abrasive Grinding Wheel Formulated ...

    African Journals Online (AJOL)

    This paper presents a study on the formulation and manufacture of abrasive grinding wheel using locally formulated silicon carbide abrasive grains. Six local raw material substitutes were identified through pilot study and with the initial mix of the identified materials, a systematic search for an optimal formulation of silicon ...

  13. Formulation and Characterization of Biodegradable Medicated ...

    African Journals Online (AJOL)

    Purpose: To formulate and evaluate biodegradable corn zein as a base for diphenhydramine hydrochloride medicated chewing gum for effective management of motion sickness. Method: Corn zein gum formulations were prepared using a fixed concentration (35 % w/w) of different plasticizer for each formulation.

  14. Formulation, Preparation, and Characterization of Polyurethane Foams

    Science.gov (United States)

    Pinto, Moises L.

    2010-01-01

    Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

  15. Formulation and evaluation of sustained release paracetamol ...

    African Journals Online (AJOL)

    From the dissolution data of the eight tablet formulations that resulted from the experimental design, a polynomial regression equation was generated from which an optimum formulation was obtained. Three different batches of granules of the \\'optimum formulation\\' were compressed into tablets at a compression force of 15 ...

  16. A Transtheoretical Approach to Case Formulation

    Science.gov (United States)

    Jose, Anita; Goldfried, Marvin

    2008-01-01

    In answer to the need for a comprehensive, systematic, yet flexible case formulation method, the present article describes the Causal Analysis and Synthesis of Events (CASE) system, a transtheoretical case formulation method. This method of functional case formulation is useful in terms of explicating the problem and identifying potential areas…

  17. Development and Evaluation of Herbal Formulations for Hair Growth

    Directory of Open Access Journals (Sweden)

    Lipi Purwal

    2008-01-01

    Full Text Available Hair formulation of Emblica officinalis (Euphorbiaceae, Bacopa, monnieri (Scrophulariaceae, Trigonella foenumgraecum (Leguminosae, Murraya koenigii (Rutaceae in various concentrations in the form of herbal oil were studied for their hair growth activity. Each drug was tested for their hair growth activity in a concentration range for 1-10% separately. Based on these results mixture of crude drugs Murraya koeniigi, leaf (Rutaceae, Bacopa monnieri, leaf (Scrophulariaceae, Trigonella foenumgraecum (Leguminosae, Murraya koenigii (Rutaceae were prepared in varying concentration in the form of herbal hair oil by three different oils preparation techniques and were tested for hair growth activity. The result revealed that the hair growth activity of each drug was found proportional to the concentration range tested. Similarly higher concentrations of drug in the formulation were found to have higher hair growth activities. But looking towards the formulation viscosity the maximum concentration of combined drug was found to be 30% at their maximum level. The formulation containing 7.5% of each drug used for the study and showed excellent hair growth activity with standard (2% minoxidil ethanolic solution by an enlargement of follicular size and prolongation of the anagen phase. It holds the promise of potent herbal alternative for minoxidil. Excellent results of hair growth were seen in formulation prepared by cloth pouch decoction method of oils preparation technique.

  18. Artificial intelligence in pharmaceutical product formulation: neural computing

    Directory of Open Access Journals (Sweden)

    Svetlana Ibrić

    2009-10-01

    Full Text Available The properties of a formulation are determined not only by the ratios in which the ingredients are combined but also by the processing conditions. Although the relationships between the ingredient levels, processing conditions, and product performance may be known anecdotally, they can rarely be quantified. In the past, formulators tended to use statistical techniques to model their formulations, relying on response surfaces to provide a mechanism for optimazation. However, the optimization by such a method can be misleading, especially if the formulation is complex. More recently, advances in mathematics and computer science have led to the development of alternative modeling and data mining techniques which work with a wider range of data sources: neural networks (an attempt to mimic the processing of the human brain; genetic algorithms (an attempt to mimic the evolutionary process by which biological systems self-organize and adapt, and fuzzy logic (an attempt to mimic the ability of the human brain to draw conclusions and generate responses based on incomplete or imprecise information. In this review the current technology will be examined, as well as its application in pharmaceutical formulation and processing. The challenges, benefits and future possibilities of neural computing will be discussed.

  19. Predicting skin penetration of actives from complex cosmetic formulations: an evaluation of inter formulation and inter active effects during formulation optimization for transdermal delivery.

    Science.gov (United States)

    Wiechers, J W; Watkinson, A C; Cross, S E; Roberts, M S

    2012-12-01

    Twenty products, containing a radiolabelled form of each active in typical cosmetic formulations, were made and applied to female human epidermal membranes mounted in Franz diffusion cells for 48 h under 'in use' conditions. The products consisted of combinations of five formulations (a hydro-alcoholic gel, an oil in water emulsion, a water in oil emulsion, a microemulsion and an oil) with four model drug actives (testosterone, hydrocortisone, 5-fluorouracil and ketoconazole). Steady-state flux appeared to be reached by 8 h and maintained for all products, other than for the microemulsions, consistent with the actives being present in the residual formulation on the skin at saturation. The recovery for each active at the end of the 48-h study (from a series of stratum corneum tape strips, the remaining skin, cumulative amount penetrating into the receptor solution, product washed from the skin and on the donor chamber cap) ranged from 86.5% to 100.6%. The rank order of the fluxes for the actives from the hydro-alcoholic gel is consistent with the known active molecular size and polarity determinants for maximum epidermal flux. Actives with similar steady-state (maximum) fluxes from a range of formulations had retention in the stratum corneum and similar transport rate constants through the stratum corneum. The microemulsion formulation significantly enhanced both the stratum corneum steady-state flux and transport rate constant for 5-fluorouracil, hydrocortisone and testosterone. The penetration flux of each active could be related to its size and polarity and appeared maximal when the actives in the different cosmetic formulations applied to the skin under 'in use' conditions were likely to remain in the residual product on the skin as a saturated solution after solvent evaporation. Enhanced penetration fluxes can be achieved by formulation selection and an appropriate choice/mix of emollients/adjuvants. The principles described here provide a framework for

  20. A conformal and covariant formulation of the Z4 system with constraint-violation damping

    CERN Document Server

    Alic, Daniela; Bona, Carles; Rezzolla, Luciano; Palenzuela, Carlos

    2011-01-01

    We present a new formulation of the Einstein equations based on a conformal and traceless decomposition of the covariant form of the Z4 system. This formulation combines the advantages of a conformal decomposition, such as the one used in the BSSNOK formulation (i.e. well-tested hyperbolic gauges, no need for excision, robustness to imperfect boundary conditions) with the advantages of a constraint-damped formulation, such as the generalized harmonic one (i.e. exponential decay of constraint violations when these are produced). We validate the new set of equations through standard tests and by evolving binary systems of black holes. Overall, the new conformal formulation leads to a better behaviour of the constraint equations and a rapid suppression of the violations when they occur. The changes necessary to implement the new conformal formulation in standard BSSNOK codes are very small as are the additional computational costs.

  1. Comparative oral bioavailability advantage from curcumin formulations.

    Science.gov (United States)

    Munjal, Bhushan; Pawar, Yogesh Bapurao; Patel, Sarsvatkumar Babulal; Bansal, Arvind Kumar

    2011-08-01

    The aim of the present study was to study the oral bioavailability of seven different formulations of curcumin (CRM). CRM formulations viz. aqueous suspension, micronized suspension, nanosuspension, amorphous solid dispersion, hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex, combination with piperine, and spray-dried CRM-milk composite were compared for oral bioavailability in male Sprague-Dawley rats at a CRM dose of 250 mg/kg body weight using a validated high-performance liquid chromatography method. Aqueous suspension provided a C max and AUC(0 - t) of 28.9 ng/ml and 26.9 ng h/ml, respectively. In comparison, statistically significant increase in the oral bioavailability was obtained with the nanosuspension, HP-β-CD inclusion complex, and amorphous solid dispersion with 251%, 567%, and 446% increase in terms of AUC(0 - t) and 405%, 415%, and 270% in terms of C max. However, no significant increase in AUC(0 - t) and C max was observed with piperine and micronized suspension. The milk composite reduced the oral bioavailability of CRM (10% and 37% in terms of AUC(0 - t) and C max). A statistically significant increase in the T max was observed with piperine and in HP-β-CD complex, while the T max was reduced for nanosuspension. The results provide interesting insights into the role of solubility enhancement and metabolism inhibition, for improving the oral bioavailability of CRM.

  2. Sublingual immunotherapy (SLIT for house dust mites does not prevent new allergen sensitization and bronchial hyper-responsiveness in allergic rhinitis children.

    Directory of Open Access Journals (Sweden)

    Jae Hyun Lim

    Full Text Available The aim of this study is to identify the effects of sublingual immunotherapy (SLIT on immunologic parameters and bronchial-hyper-responsiveness in children with allergic rhinitis to house-dust mite (HDM, through long-term follow-up cohort.Among the Allergic Rhinitis Cohort Study for Kids, pediatric patients who visited the hospital for rhinitis symptoms and proven allergy to HDM through skin prick test were studied. In this cohort, 37 patients received SLIT more than 3-years (SLIT group, and 184 patients received only pharmacologic therapy (non-SLIT group were included in this study. The results of skin prick test, eosinophil percent and count, total immunoglobulin E (IgE, and bronchial provocation test at initial and 3-year followed-up were compared in the two groups.After 3 year follow-up, only the serum eosinophil percent decreased more significantly in SLIT group than that in the non-SLIT group. New-sensitization rate other than HDM between SLIT and non-SLIT group did not show any significant differences. The distribution of sensitized allergen other than HDM showed increasing tendency after 3 years in both groups. Older age and a small number of sensitized allergen affected the improvement of bronchial hyper-responsiveness regardless of SLIT.HDM SLIT in allergic rhinitis children for 3 years in Korea does not affect prevention of new sensitization and poly-sensitization rate increment, and improvement of bronchial hyper-responsiveness.

  3. Sublingual immunotherapy (SLIT) for house dust mites does not prevent new allergen sensitization and bronchial hyper-responsiveness in allergic rhinitis children.

    Science.gov (United States)

    Lim, Jae Hyun; Kim, Jin Youp; Han, Doo Hee; Lee, Chul Hee; Hong, Seung-No; Wee, Jee Hye; Park, Sue K; Rhee, Chae-Seo

    2017-01-01

    The aim of this study is to identify the effects of sublingual immunotherapy (SLIT) on immunologic parameters and bronchial-hyper-responsiveness in children with allergic rhinitis to house-dust mite (HDM), through long-term follow-up cohort. Among the Allergic Rhinitis Cohort Study for Kids, pediatric patients who visited the hospital for rhinitis symptoms and proven allergy to HDM through skin prick test were studied. In this cohort, 37 patients received SLIT more than 3-years (SLIT group), and 184 patients received only pharmacologic therapy (non-SLIT group) were included in this study. The results of skin prick test, eosinophil percent and count, total immunoglobulin E (IgE), and bronchial provocation test at initial and 3-year followed-up were compared in the two groups. After 3 year follow-up, only the serum eosinophil percent decreased more significantly in SLIT group than that in the non-SLIT group. New-sensitization rate other than HDM between SLIT and non-SLIT group did not show any significant differences. The distribution of sensitized allergen other than HDM showed increasing tendency after 3 years in both groups. Older age and a small number of sensitized allergen affected the improvement of bronchial hyper-responsiveness regardless of SLIT. HDM SLIT in allergic rhinitis children for 3 years in Korea does not affect prevention of new sensitization and poly-sensitization rate increment, and improvement of bronchial hyper-responsiveness.

  4. A Retrospective Cohort Study of Obstetric Outcomes in Opioid-Dependent Women Treated with Implant Naltrexone, Oral Methadone or Sublingual Buprenorphine, and Non-Dependent Controls.

    Science.gov (United States)

    Kelty, Erin; Hulse, Gary

    2017-07-01

    Opioid pharmacotherapies play an important role in the treatment of opioid-dependent women; however, very little is known about the safety of naltrexone in pregnant patients. This study examined the obstetric health of opioid-dependent women who were treated with implant naltrexone during pregnancy, and compared them with women treated with methadone and/or buprenorphine and a cohort of non-opioid-dependent controls. Women treated with implant naltrexone, oral methadone or sublingual buprenorphine between 2001 and 2010, along with a cohort of age-matched controls, were linked with records from midwives, hospital and emergency departments (EDs) and the death registry to identify pregnancy and health events that occurred during pregnancy and in the post-partum period. Overall rates of pregnancy loss (requiring hospital or ED attendance) were significantly elevated in naltrexone-treated women compared with buprenorphine-treated women (p = 0.018) and controls (p buprenorphine groups, and neither were overall complications during pregnancy and labour. Overall rates of complications during pregnancy were significantly higher in the naltrexone-treated women than in the controls. Opioid-dependent women treated with naltrexone implant had higher rates of birth than the other three groups (methadone- or buprenorphine-treated women, or age-matched controls). Overall rates of complications during pregnancy were elevated in naltrexone-treated women when compared with the control group, but were generally not significantly different to rates in methadone- or buprenorphine-treated women.

  5. Opioid substitution treatment with sublingual buprenorphine in Manipur and Nagaland in Northeast India: what has been established needs to be continued and expanded

    Directory of Open Access Journals (Sweden)

    Sharma Charan

    2009-02-01

    Full Text Available Abstract Manipur and Nagaland in northeast India report an antenatal HIV prevalence of > 1% and the current HIV prevalence among injecting drug users is 24% and 4.5% respectively. Through support from DFID's Challenge Fund, Emmanuel Hospital Association (EHA established thirteen drop-in-centres across the two states to deliver opioid substitution treatment with sublingual buprenorphine for 1200 injecting drug users. Within a short span of time the treatment has been found to be attractive to the clients and currently 1248 injecting opioid users are receiving opioid substitution treatment. The project is acceptable to the drug users, the families, the communities, religious as well as the militant groups. The treatment centres operate all days of the week, have trained staff members, utilize standardized protocols and ensure a strict supervised delivery system to prevent illicit diversion of buprenorphine. The drug users receiving the substitution treatment are referred to HIV voluntary counselling and testing. As this treatment has the potential to change HIV related risk behaviours, what has been established in the two states needs to be continued and expanded with the support from the Government of India.

  6. Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: A retrospective, real-world database analysis.

    Science.gov (United States)

    Zielen, S; Devillier, P; Heinrich, J; Richter, H; Wahn, U

    2018-01-01

    Allergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT. To assess the real-world, long-term efficacy of grass pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression. In a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression analysis was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups. After applying all selection criteria, 2851 SLIT and 71 275 control patients were selected for the study. After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pretreatment period) in SLIT tablet group than in the non-AIT group (PReal-world treatment of AR patients with grass pollen SLIT tablets was associated with slower AR progression, less frequent asthma onset, and slower asthma progression. © 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.

  7. Sublingual administration of bacteria-expressed influenza virus hemagglutinin 1 (HA1) induces protection against infection with 2009 pandemic H1N1 influenza virus.

    Science.gov (United States)

    Shim, Byoung-Shik; Choi, Jung-Ah; Song, Ho-Hyun; Park, Sung-Moo; Cheon, In Su; Jang, Ji-Eun; Woo, Sun Je; Cho, Chung Hwan; Song, Min-Suk; Kim, Hyemi; Song, Kyung Joo; Lee, Jae Myun; Kim, Suhng Wook; Song, Dae Sub; Choi, Young Ki; Kim, Jae-Ouk; Nguyen, Huan Huu; Kim, Dong Wook; Bahk, Young Yil; Yun, Cheol-Heui; Song, Man Ki

    2013-02-01

    Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a well-established bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics.

  8. First report of angio-oedema subsequent to the administration of allergen specific sublingual immunotherapy for the management of equine hypersensitivity dermatitis.

    Science.gov (United States)

    Scholz, Fiona M; Burrows, Amanda K; Muse, Russell

    2016-10-01

    Sublingual immunotherapy (SLIT) offers an alternative mode of allergen delivery to subcutaneous immunotherapy (SCIT) with the aim of inducing immunological tolerance. Currently, there are no published reports regarding the efficacy or safety of SLIT in horses. To describe the first case of several adverse events occurring in a horse subsequent to the repeat administration of SLIT. A seven-year-old, warmblood mare with a confirmed diagnosis of equine hypersensitivity dermatitis (EHD). Immunotherapy was recommended for management of EHD. Due to the temperament of the horse, the owner elected to proceed with SLIT. Thirty six hours after commencing SLIT, the mare developed scleral oedema, moderate dyspnoea and abdominal discomfort. SLIT was withdrawn for 10 days and re instituted using a ten-fold dilution of the original vaccine. Localized oedema and swelling of the tongue developed within 12 h of administration. At this juncture, SLIT was withdrawn. The horse was rechallenged with the SLIT allergen vehicle, 50% glycerine and no adverse reactions occurred. SCIT was commenced using the same allergens and no adverse events occurred with repeated administration. To the best of the authors' knowledge, this is the first reported case of adverse reactions developing subsequent to the administration of SLIT for the management of EHD. © 2016 ESVD and ACVD.

  9. In vivo photoprotective effects of cosmetic formulations containing UV filters, vitamins, Ginkgo biloba and red algae extracts.

    Science.gov (United States)

    Mercurio, D G; Wagemaker, T A L; Alves, V M; Benevenuto, C G; Gaspar, L R; Maia Campos, P M B G

    2015-12-01

    The aim of this study was to assess the photoprotective effects of cosmetic formulations containing UV filters, red algae, Porphyra umbilicalis, extracts and combinations of the extract with vitamins and Ginkgo biloba through the use of in vivo preclinical studies. For this study, 4 groups of 4 hairless mice each were treated with topical formulations applied on the dorsum for 5 days as follows: group 1 - control (no treatment); group 2 - application of the formulation F (sunscreen formulation containing only UV filters); group 3 - application of the formulation FA (sunscreen formulation with red algae extract); and group 4 - application of the formulation FVGA (sunscreen formulation with red algae extract, G. biloba and vitamins A, C and E). The effects of these formulations were evaluated by determining the transepidermal water loss (TEWL) and erythema index. Apoptosis was detected by immunohistochemical staining with anti-p53 and anti-caspase-3 antibodies. The results showed that the formulations protected the skin from erythema when exposed to UV radiation. The group that received the formulation FVGA presented a greater TEWL than did the other groups, suggesting that this formulation was involved in cell renewal. Immunohistochemical analysis showed that UV radiation caused an increase in the expression of p53 and active caspase-3, confirming that the damage caused by UV radiation exposure led to apoptosis. The application of all formulations studied resulted in a statistically significant reduction in the expression of p53 and caspase-3, with a more pronounced effect observed following treatment with FA. In conclusion, extracts from the red algae P. umbilicalis could be considered effective ingredients to be used in sunscreen formulations. The combination of vitamins A, E, C and G. biloba along with red algae extracts can improve significantly the performance of the sunscreens, preventing UV-induced DNA damage and inflammation. Thus, they should be considered

  10. Formulation and characterization of gastroretentive discs containing famotidine

    OpenAIRE

    Jignyasha Amitkumar Raval; Patel,Madhabhai M

    2011-01-01

    In this work a different type of formulation, as disc, containing a selected mucoadhesive polymer, fillers, and binders were investigated for their potential as a mucoadhesive gastroretentive delivery system to deliver famotidine in the stomach. Various types of hydrophilic diluents were evaluated for their swelling and mucoadhesive property and one (polyvinylpyrrolidone, PVP) was selected to combine with the selected mucoadhesive polymer (polyethylene oxide, PEO). Discs with different ratios...

  11. Formulation and pilot scale production of low-trans vanaspati with modified polyunsaturated fatty acids content.

    Science.gov (United States)

    Nejatian, Mohammad; Nikoopour, Houshang; Mohammadi, Teimour

    2015-08-01

    Pilot scale production of low-trans vanaspati through a combination of techniques including non-selective hydrogenation of palmolein and physical blending of 3 vegetable oils, namely Canola, soybean and sunflower oils was investigated. Six formulations (A-F) of trans-free vanaspati were prepared. The fatty acid composition, peroxide value, acid value, iodine value, slip melting point (SMP), solid fat content (SFC) at 10-40 °C and oil/oxidative stability of the formulations were evaluated. The percentage of trans-fatty acids obtained for vanaspati formulations were within the value recommended by WHO (vanaspati formulations ranged from 22.96 to 30.11 %. Among the six formulations, A showed the significant percentage of SFA. The highest and the Lowest of linolenic acid contents were obtained for samples E (4.36 %) and F (0.28 %). Percentage of the monounsaturated fatty acids (MUFA) of the vanaspati formulations suggested an order from the highest to lowest as: A > C > E > F > D > B formulations. B formulation had the highest significant percentage of PUFA, followed by D, E, F, C, and A formulations. Only A vanaspati had the induction periods (IP) of higher than commercial low-trans vanaspati, while the lowest stability time belonged to sample B (10.20 h). SMP of all the vanaspati formulations was higher than the commercial low-trans vanaspati, but less than 40 °C. Although A and E formulations contained lower SFA than the commercial low-trans vanaspati, they indicated higher SFC at 20-40 °C. According to the above information, E and A formulations could be recommended as suitable formulations for further research in a larger scale.

  12. Cream formulation impact on topical administration of engineered colloidal nanoparticles.

    Directory of Open Access Journals (Sweden)

    Benedetta Santini

    Full Text Available In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide nanoparticles (MNP coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.

  13. Cream formulation impact on topical administration of engineered colloidal nanoparticles.

    Science.gov (United States)

    Santini, Benedetta; Zanoni, Ivan; Marzi, Roberta; Cigni, Clara; Bedoni, Marzia; Gramatica, Furio; Palugan, Luca; Corsi, Fabio; Granucci, Francesca; Colombo, Miriam

    2015-01-01

    In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.

  14. Summary compilation of shell element performance versus formulation.

    Energy Technology Data Exchange (ETDEWEB)

    Heinstein, Martin Wilhelm; Hales, Jason Dean (Idaho National Laboratory, Idaho Falls, ID); Breivik, Nicole L.; Key, Samuel W. (FMA Development, LLC, Great Falls, MT)

    2011-07-01

    This document compares the finite element shell formulations in the Sierra Solid Mechanics code. These are finite elements either currently in the Sierra simulation codes Presto and Adagio, or expected to be added to them in time. The list of elements are divided into traditional two-dimensional, plane stress shell finite elements, and three-dimensional solid finite elements that contain either modifications or additional terms designed to represent the bending stiffness expected to be found in shell formulations. These particular finite elements are formulated for finite deformation and inelastic material response, and, as such, are not based on some of the elegant formulations that can be found in an elastic, infinitesimal finite element setting. Each shell element is subjected to a series of 12 verification and validation test problems. The underlying purpose of the tests here is to identify the quality of both the spatially discrete finite element gradient operator and the spatially discrete finite element divergence operator. If the derivation of the finite element is proper, the discrete divergence operator is the transpose of the discrete gradient operator. An overall summary is provided from which one can rank, at least in an average sense, how well the individual formulations can be expected to perform in applications encountered year in and year out. A letter grade has been assigned albeit sometimes subjectively for each shell element and each test problem result. The number of A's, B's, C's, et cetera assigned have been totaled, and a grade point average (GPA) has been computed, based on a 4.0-system. These grades, combined with a comparison between the test problems and the application problem, can be used to guide an analyst to select the element with the best shell formulation.

  15. Histometría de la glándula sublingual de ratones (Mus musculus machos y hembras infectados con la cepa RAL del parásito de Chagas, Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Sérgio de Albuquerque

    2008-06-01

    Full Text Available Analizamos morfológica e histométricamente la glándula sublingual de ratones infectados con la cepa RAL del Trypanosoma cruzi, en machos y hembras. Usamos ratones albinos (Mus musculus, variedad Swiss, inoculados con 2x104 tripomastigotes sanguíneos de la cepa RAL del T. cruzi.. Sacrificamos los animales en el pico de la parasitemia (12º día y fijamos las glándulas sublinguales en ALFAC. Los cortes histológicos teñidos con HE fueron evaluados histométricamente (cariometría y estereología. La parasitemia fue más elevada en las hembras. Histopatológicamente, los "ácinos" (acini de los animales infectados eran menores, con escasa secreción, y conductos estriados menores. Los núcleos de las "medialunas" eran menores y había nidos de amastigotes en el citoplasma. Cariométricamente, los núcleos de los ácinos, medialunas y conductos estriados eran menores en los ratones infectados. Estereológicamente, los volúmenes relativos ocupados por ácinos y conductos estriados fueron menores e, inversamente, fue mayor el volumen para el tejido conjuntivo de los machos infectados. Las densidades de superficie de ácinos y conductos fueron mayores, y el diámetro y el espesor de la pared menores, en este grupo. Por otro lado, la densidad de ácinos fue menor, y las de los conductos estriados y tejido conjuntivo, fueron mayores en las hembras infectadas. Las densidades de superficie de ácinos y conductos estriados fueron mayores, mientras que el diámetro y espesor de la pared de los ácinos fueron menores (y las de los conductos estriados mayores, en este grupo. La cepa RAL del T. cruzi causó un cuadro general de atrofia general en la glándula sublingual, con numerosos nidos de parásitos.Histometry of the sublingual gland in male and female mice (Mus musculus infected with the RAL strain of the Chagas parasite, Trypanosoma cruzi. The aim of this work was to analyze histologically and histometrically the sublingual gland of mice infected

  16. On fictitious domain formulations for Maxwell's equations

    DEFF Research Database (Denmark)

    Dahmen, W.; Jensen, Torben Klint; Urban, K.

    2003-01-01

    We consider fictitious domain-Lagrange multiplier formulations for variational problems in the space H(curl: Omega) derived from Maxwell's equations. Boundary conditions and the divergence constraint are imposed weakly by using Lagrange multipliers. Both the time dependent and time harmonic...... formulations of the Maxwell's equations are considered. and we derive well-posed formulations for both cases. The variational problem that arises can be discretized by functions that do not satisfy an a-priori divergence constraint....

  17. Formulation of disperse systems science and technology

    CERN Document Server

    Tadros, Tharwat F

    2014-01-01

    This book presents comprehensively the science and technology behind the formulation of disperse systems like emulsions, suspensions, foams and others. Starting with a general introduction, the book covers a broad range of topics like the role of different classes of surfactants, stability of disperse systems, formulation of different dispersions, evaluation of formulations and many more. Many examples are included, too. Written by the experienced author and editor Tharwart Tadros, this book is indispensable for every scientist working in the field.

  18. Necessity of rethinking oral pediatric formulations

    DEFF Research Database (Denmark)

    Bar-Shalom, Daniel

    2014-01-01

    This commentary reviews the difficulties in formulating oral products for children. The significance of the fragmentation of the pediatric population in terms of development and ability to ingest different dosage formulations is examined. It is postulated that a flexible formulation, acceptable...... by all patient groups, is needed, and an automated compounding concept is proposed. The finishing of the formulation is done at the dispensing pharmacy using an automated process. The individual components (pudding-like carrier, microencapsulated drug, and the dispensing robot and its software...

  19. Quality of life improvement after a three-year course of sublingual immunotherapy in patients with house dust mite and grass pollen induced allergic rhinitis: results from real-life.

    Science.gov (United States)

    Novakova, Silviya Mihaylova; Staevska, Maria Toncheva; Novakova, Plamena Ivanova; Yoncheva, Manuela Dimitrova; Bratoycheva, Maria Stoykova; Musurlieva, Nina Mihaylova; Tzekov, Valeri Dimitrov; Nicolov, Dimitar Georgiev

    2017-09-29

    Along with its high prevalence, the burden of allergic rhinitis rests upon the serious impact on quality of life of patients. Allergic rhinitis is associated with impairments in daily activities, work and school performance, and practical problems. Patients suffer from sleep disorders and emotional problems. Тhe advantages of sublingual immunotherapy on quality of life have only recently begun to emerge. The objective of this prospective real-life study was to evaluate the effect of a three-year course of sublingual immunotherapy with house dust mite (HDM) and grass pollen extracts on quality of life in adults with allergic rhinitis. A total number of 191 adult patients [105 (54,979%) men; mean age 27.3 years (SD-6.14)] with moderate to severe allergic rhinitis and clinically relevant sensitization to house dust mites or grass pollen were prospectively evaluated in the course of management of their disease. Health-related quality of life was assessed by Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after three-year course of sublingual immunotherapy. The mean overall Qol score assessed at baseline and at the end of the third year of treatment decreased significantly in patients treated with HDM extract (from 2.95 to 0.76) as well as with Grass pollen extract (from 2.83 to 1.22) (р life provided evidence that a three-year course of SLIT with HDM extract as well as with grass pollen extract significantly increased QoL in patients with allergic rhinitis.

  20. MOND and its bimetric formulation

    CERN Document Server

    Milgrom, Mordehai

    2013-01-01

    I first give a succinct account of the MOND paradigm--emphasizing the centrality of scale invariance in the nonrelativistic, deep-MOND limit--and describing rudiments of its phenomenology. I then present my credo, and some generalities, concerning existing MOND theories. Then I concentrate on one relativistic formulation of MOND in the form of a bimetric theory (BIMOND). I describe its various limits: the weak field, with application to gravitational waves, the nonrelativistic limit, and their further deep-MOND (low acceleration) limits, which are scale invariant. Other aspects of BIMOND that have been explored are aspects of cosmology, matter fluctuations in cosmology, and matter-twin-matter interactions. BIMOND remains largely unexplored, despite its promise in several regards: It tends to GR for a0 goes to 0 (a0 is the MOND constant); it has a simple nonrelativistic limit; it describes gravitational lensing correctly; and, it has a generic appearance of a cosmological-constant term that is of order a0^2/c^...

  1. Determination of hormonal combination for increased multiplication ...

    African Journals Online (AJOL)

    Eight hormonal combinations were formulated and tested using a completely randomized design with three replicates in the tissue culture laboratory. Ten shoot tips from in-vitro raised plantlets were excised and transferred to each of these hormonal combinations. The effect of hormonal combinations was variety dependant ...

  2. Starch industry wastewater-based stable Bacillus thuringiensis liquid formulations.

    Science.gov (United States)

    Brar, Satinder K; Verma, M; Tyagi, R D; Valéro, J R; Surampalli, R Y

    2005-12-01

    Liquid formulations were developed from Bacillus thuringiensis (Bt)-fermented broths of starch industry wastewater (SIW) and of soya medium. Stability studies were carried out for 1 yr. Storage stability was tested by studying various physical and chemical (e.g., viscosity, particle size, corrosion, and suspendibility) and biological (e.g., microbial contamination, viable spores, and entomotoxicity) parameters at different pH levels and temperatures. Three suspending agents, sorbitol, sodium monophosphate, and sodium metabisulfite, were added to fermented broth in different concentrations. Sorbitol and sodium monophosphate in the ratio 3:1 was the best suspending agent combination for both formulations. Starch industry wastewater fermentation yielded cell and viable spore counts 10- and 4-fold greater than those from soya medium, respectively, and a 1.7-fold increase in entomotoxicity. However, both formulations started deteriorating at pH 6 and 6.5 and 40 and 50 degrees C. There were no signs of corrosion and microbial contamination in both types of formulations.

  3. Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets

    Directory of Open Access Journals (Sweden)

    Fatemeh Fattahi

    2013-02-01

    Full Text Available Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Results: Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pH<6, friability < 1%, water percentage < 0.5% and accurate content uniformity. In panel test, both of combination flavors; (orange - lemon and (strawberry - raspberry had good acceptability. Conclusion: The prepared tablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates.

  4. Characterisation of dry powder inhaler formulations using atomic force microscopy.

    Science.gov (United States)

    Weiss, Cordula; McLoughlin, Peter; Cathcart, Helen

    2015-10-15

    Inhalation formulations are a popular way of treating the symptoms of respiratory diseases. The active pharmaceutical ingredient (API) is delivered directly to the site of action within the deep lung using an inhalation device such as the dry powder inhaler (DPI). The performance of the formulation and the efficiency of the treatment depend on a number of factors including the forces acting between the components. In DPI formulations these forces are dominated by interparticulate interactions. Research has shown that adhesive and cohesive forces depend on a number of particulate properties such as size, surface roughness, crystallinity, surface energetics and combinations of these. With traditional methods the impact of particulate properties on interparticulate forces could be evaluated by examining the bulk properties. Atomic force microscopy (AFM), however, enables the determination of local surface characteristics and the direct measurement of interparticulate forces using the colloidal probe technique. AFM is considered extremely useful for evaluating the surface topography of a substrate (an API or carrier particle) and even allows the identification of crystal faces, defects and polymorphs from high-resolution images. Additionally, information is given about local mechanical properties of the particles and changes in surface composition and energetics. The assessment of attractive forces between two bodies is possible by using colloidal probe AFM. This review article summarises the application of AFM in DPI formulations while specifically focussing on the colloidal probe technique and the evaluation of interparticulate forces. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Quality evaluation of extemporaneous delayed-release liquid formulations of lansoprazole.

    Science.gov (United States)

    Melkoumov, Alexandre; Soukrati, Amina; Elkin, Igor; Forest, Jean-Marc; Hildgen, Patrice; Leclair, Grégoire

    2011-11-01

    The quality attributes of extemporaneous delayed-release liquid formulations of lansoprazole for oral administration were evaluated. A novel liquid formulation (3 mg/mL) of Prevacid FasTab in an Ora-Blend vehicle was prepared and compared with the Prevacid FasTab 30 mg and Prevacid-sodium bicarbonate 1 M formulation (3 mg/mL). The latter formulation was combined with hydrochloric acid 0.1 N, and the remaining lansoprazole content was assayed by high-performance liquid chromatography (HPLC). A batch of delayed-release liquid formulation was prepared to evaluate content uniformity. For content assay, three samples were prepared for each evaluated condition and each sample was analyzed in triplicate by HPLC. The lansoprazole in the sodium bicarbonate formulation was extensively degraded by quantities of hydrochloric acid 0.1 N in excess of 100 mL. Storage time and temperature had a significant effect on lansoprazole stability in the Ora-Blend formulation. The drug remained stable for seven days when the formulation was stored at 4.5-5.5 °C, but storage at 21-22 °C or the reduction of pH with citric acid accelerated lansoprazole degradation. The amount of lansoprazole released from the Ora-Blend formulation during the buffer stage of the dissolution test decreased with increases in formulation storage time, in formulation storage temperature, and in the amount of lansoprazole released and degraded during the acid stage of the test. An extemporaneous formulation consisting of lansoprazole microgranules in Ora-Blend maintained acceptable quality attributes when stored for three days at 4.5-5.5 °C.

  6. Effects of irradiation on intracellular protein synthesis in demilune of mouse sublingual gland; Study of electron microscopic autoradiography with [sup 3]H-leucine

    Energy Technology Data Exchange (ETDEWEB)

    Ohki, Ikuko; Nasu, Masanori; Matsunaga, Hajime; Furumoto, Keiichi (Nippon Dental Univ., Tokyo (Japan))

    1994-08-01

    The effects of radiation on amino acid transport in demilune of the sublingual glands were examined in mice. After 10 Gy X-ray irradiation to the submandibular region, [sup 3]H-leucine was administered to these mice. Three days after irradiation, light microscopic autoradiograms and electron microscopic autoradiograms were obtained to determine the silver grain count in demilune and the distribution of silver grain in the organelles of these cells involved in protein synthesis. Both non-irradiated and irradiated groups showed a peak count 30 minutes after the administration of [sup 3]H-leucine and a tendency to decrease in the count thereafter. The magnitude of the chronological change in this parameter was smaller in the irradiated group than in the non-irradiated group. The percentage of silver grain in the rough endoplasmic reticulum also reached a peak 30 minutes after [sup 3]H-leucine administration in both non-irradiated and irradiated groups. Thereafter the percentage tended to decrease with time in the non-irradiated group. In the irradiated group, on the other hand, the percentage showed little change from the peak level at 60, 120, and 180 minutes. In the non-irradiated group, the percentage of silver grain in the Golgi apparatus was relatively high at 30 and 60 minutes. The percentage tended to be low at 120 and 180 minutes in the irradiated group. In the non-irradiated group, the percentage of silver grain in condencing vacuoles reached a peak at 60 minutes and decreased gradually thereafter. This parameter reached a peak at 30 minutes in the irradiated group. The percentage of silver grain in the secretory granules increased with time in both non-irradiated and irradiated groups. At 30 and 60 minutes, the percentage was significantly higher in the irradiated group than in the non-irradiated group. At 180 minutes, however, it was significantly lower in the irradiated group than in the non-irradiated group. (author).

  7. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings

    Directory of Open Access Journals (Sweden)

    Jie Li

    2017-06-01

    Full Text Available Although arctigenin (AG has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK profiles of AG with different drug-delivery manners, including intravenous (i.v, hypodermic injection (i.h, and sublingual (s.l administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate < 1 h, a high absorption degree (absolute bioavailability > 100%, and a strong elimination ability (t1/2 < 2 h. The tissue distributions of AG at different time points after i.h showed that the distribution of AG in rat tissues is rapid (2.5 h to reach the peak and wide (detectable in almost all tissues and organs. The AG concentration in the intestine was the highest, followed by that in the heart, liver, pancreas, and kidney. In vitro, AG were incubated with human, monkey, beagle dog and rat liver microsomes. The concentrations of AG were detected by UPLC-MS/MS at different time points (from 0 min to 90 min. The percentages of AG remaining in four species’ liver microsomes were human (62 ± 6.36% > beagle dog (25.9 ± 3.24% > rat (15.7 ± 9% > monkey (3.69 ± 0.12%. This systematic investigation of pharmacokinetic profiles of arctigenin (AG in vivo and in vitro is worthy of further exploration.

  8. Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis.

    Science.gov (United States)

    Didier, Alain; Worm, Margitta; Horak, Friedrich; Sussman, Gordon; de Beaumont, Olivier; Le Gall, Martine; Melac, Michel; Malling, Hans-Jorgen

    2011-09-01

    Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies. We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR (index of reactivity) 5-grass-pollen SLIT tablets (Oralair) compared with placebo assessed by using the average adjusted symptom score (AAdSS) at season 3 in adults with grass pollen-induced rhinoconjunctivitis. Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons. The primary outcome was the AAdSS, a symptom score adjusted for rescue medication use, after 3 consecutive treatment seasons. Secondary outcomes were symptoms and rescue medication score, quality-of-life, and safety assessments. The mean AAdSS was reduced by 36.0% and 34.5% at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups, respectively, compared with that in the placebo group (P ISSs and the medication score, with a marked improvement in quality of life for both active groups compared with the placebo group at season 3. Most treatment-emergent adverse events were local reactions expected with SLIT, decreasing in number and intensity in each treatment season. Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated, with reduction in symptoms and rescue medication use. The treatment was well tolerated. Adverse events decreased in number and intensity over the 3 seasons. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  9. Urinary tract infections in women with stress urinary incontinence treated with transobturator suburethral tape and benefit gained from the sublingual polibacterial vaccine.

    Science.gov (United States)

    Lorenzo Gómez, María F; Collazos Robles, Rafael E; Virseda Rodríguez, Álvaro J; García Cenador, María B; Mirón Canelo, José A; Padilla Fernández, Bárbara

    2015-08-01

    Stress urinary incontinence (SUI) and recurrent urinary tract infections (RUTIs) are highly prevalent diseases. Our purpose was to investigate the relationship between RUTIs and surgical correction of SUI with transobturator suburethral tape (TOT) and to describe the benefit gained from a sublingual polibacterial preparation on RUTIs developed after TOT. A retrospective study was performed on 420 women who underwent TOT surgery due to SUI between April 2003 and October 2011. Group A: patients without urinary tract infections (UTIs) before TOT (n = 294). Group B: patients with UTIs before TOT (n = 126). age, personal history, number of UTIs/month prior to and after surgery, appearance of urgent urinary incontinence (UUI) with or without UTIs, response to International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and Short Form 36 (SF-36) questionnaires. Group A: 85% dry; 5% UUI; 4% de novo UTIs with good response to antibiotics over 6 days. No RUTIs during the follow-up period, 2% with sporadic UTIs. Group B: 47.61% RUTIs; 52.39% sporadic UTIs; greater incidence of diabetes mellitus (p < 0.0025) and smoking (p < 0.0031) than group A. After TOT: 79.36% dry; 10% RUTIs. After treatment with antibiotics for 6 days and bacterial preparation for 3 months, 82% of patients did not have a UTI anymore. Postoperative cystourethrogram revealed 38% of nondiagnosed cystoceles before TOT. No patient had a postvoiding volume greater than 100 cm(3) after TOT. Improvement of ICIQ-SF (p < 0.001) and SF-36 (p < 0.0004) in both groups. After eliminating bias associated with the tape, the technique and the surgeon's skills, SUI correction may decrease the number of UTIs and improve the quality of life. UTIs disappeared in 82% of patients with RUTIs after TOT.

  10. A New Resistance Formulation for Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Ji-Huan He

    2008-01-01

    Full Text Available A new resistance formulation for carbon nanotubes is suggested using fractal approach. The new formulation is also valid for other nonmetal conductors including nerve fibers, conductive polymers, and molecular wires. Our theoretical prediction agrees well with experimental observation.

  11. Formulation and characterization of caffeine biodegradable chewing ...

    African Journals Online (AJOL)

    chewing gums are formulated using synthetic or natural elastomers. The synthetic or ... gums with synthetic ingredients and sugar-free coating and the ..... Food Technol 1978;. 32: 62-66. 16. Mehta FM, Trivedi P. Formulation and characterization of biodegradable medicated chewing gum delivery system for motion sickness ...

  12. Advanced Query Formulation in Deductive Databases.

    Science.gov (United States)

    Niemi, Timo; Jarvelin, Kalervo

    1992-01-01

    Discusses deductive databases and database management systems (DBMS) and introduces a framework for advanced query formulation for end users. Recursive processing is described, a sample extensional database is presented, query types are explained, and criteria for advanced query formulation from the end user's viewpoint are examined. (31…

  13. Anti-lipase activity of Kampo formulations, coptidis rhizoma and its alkaloids against Propionibacterium acnes.

    Science.gov (United States)

    Higaki, S; Nakamura, M; Morohashi, M; Hasegawa, Y; Yamagishi, T

    1996-05-01

    Anti-lipase activity of Kampo formulations, Coptidis Rhizoma (CR), and its alkaloids against Propionibacterium acnes were examined in vitro. The amounts of propionic and butyric acids in the medium were measured as growth and lipase activity of P. acnes, respectively. In tributyrin-PYG medium with each concentration of Kampo formulation, CR, or the alkaloids added, the production of propionic acid was suppressed remarkably more than that of butyric acid. The suppression of production of these acids by CR was higher than that of the alkaloids. Furthermore, no lipase-negative colonies were found on the medium to which Kampo formulations were added. From these observations, we concluded that not only Kampo formulations and CR, but also their alkaloids, showed suppression of growth of P. acnes, which reduced anti-lipase activity. Furthermore, it was suggested that Kampo formulations and Kampo crude drugs with anti-lipase activity to P. acnes should be synergistic when their ingredients are combined.

  14. Dynamic dissolution-/permeation-testing of nano- and microparticle formulations of fenofibrate

    DEFF Research Database (Denmark)

    Sironi, Daniel; Rosenberg, Jörg; Bauer-Brandl, Annette

    2017-01-01

    , a microparticle formulation (Lipidil® 200mg) and a nanoparticle formulation (LIPIDIL 145 ONE®) using a pair of side-by side diffusion cells separated by a cellulose hydrate membrane. Under such dynamic conditions, transient supersaturation arising from the nanoparticle formulation could be demonstrated......-/ or nanoparticle-formulation was tested. Nondissolved nano-/microparticles served as a reservoir helping to maintain high levels of molecularly dissolved drug, which in turn caused high and constant permeation rates. The micelle-bound drug may also serve as a drug-reservoir, yet of subordinate importance as long...... as there are nano-/microparticles present. Despite the limitations of the current experimental set-up, combined dissolution-/permeation-testing appears a valuable new tool to promote mechanistic understanding during formulation development. Last but not least, the in vitro dissolution and permeation behavior...

  15. Rheology of urethane dimethacrylate and diluent formulations.

    Science.gov (United States)

    Silikas, N; Watts, D C

    1999-07-01

    The purpose of this study was to measure the viscosity of resin formulations and investigate the relationship between diluent percentage and temperature. Resin formulations were prepared using UDMA and either TEGDMA or HEMA, or HPMA, as diluents at different percentages. Viscosities were obtained with a Bohlin Rheometer at 23 degrees C for all formulations, and at 37 and 60 degrees C for selected formulations. The viscosity of the formulations exhibited Newtonian behaviour and decreased as the percentage of the diluent monomer increased, especially up to 40% of diluent. Linear regressions relating log(viscosity) and mass percent diluent, were obtained in the range 20-80% diluent. Viscosity also decreased as the temperature increased. Activation energies were calculated from Arrhenius plots, and ranged from 16.2-23.4 kJ mol-1. The viscosity of the resins controls the flow properties and thus has a significant effect on the deployment of the respective monomers.

  16. Corrigendum: The loudest event statistic: general formulation, properties and applications

    Science.gov (United States)

    Biswas, Rahul; Brady, Patrick R.; Creighton, Jolien D. E.; Fairhurst, Stephen; Mendell, Gregory; Privitera, Stephen

    2013-04-01

    The loudest event statistic, a method by which the rate at which events occur can be deduced from the significance of the most significant event (or loudest event), has been employed in several papers describing the search for gravitational waves produced by coalescing compact binaries in data from the LIGO and Virgo observatories. The paper ‘The loudest event statistic: general formulation, properties and applications’ (Biswas et al 2009 Class. Quantum Grav. 26 175009) presents a general formulation of the loudest event statistic and addresses topics on the estimation of rate intervals, on combining multiple experiments, and on marginalizing over uncertainties in parameters. A conceptual error in section 5 of Biswas et al (2009) led to invalid results regarding the marginalization over uncertainties in the averaged detection efficiency; specifically its equations (23) and (24) are incorrect, as are its equations (25) and (27). This corrigendum presents a correct treatment of the marginalization of uncertainties in the estimated detection efficiency.

  17. Modeling surface tension using a ghost fluid technique within a volume of fluid formulation

    Energy Technology Data Exchange (ETDEWEB)

    Francois, M. M. (Marianne M.); Kothe, D. B. (Douglas B.); Cummins, S. J. (Sharen J.)

    2004-01-01

    Ghost fluid methods (GFM) are a viable approach for imposing sharp boundary conditions on interfaces that are arbitrarily embedded within the computational mesh. All GFM to date are formulated with an interface distance function that resides within a level-set (LS) framework. Recently we proposed a technique for reconstructing distance functions from volume fractions. This technique enables the exploitation of GFM within a volume of fluid formulation for modeling an interfacial phenomenon like surface tension. Combining GFM with a volume of fluid (VOF) formulation is attractive because of the VOF method's superior mass conservation and because of the ability of GFM to maintain sharp jump conditions. The continuum surface tension force (CSF) method, however, has the propensity to produce smooth jump. In the following, the combined VOF-GFM and more classical VOF-CSF formulations are compared and contrasted. Static and dynamic numerical results are used to illustrate our findings and support our claims.

  18. Prophylactic Sublingual Immunization with Mycobacterium tuberculosis Subunit Vaccine Incorporating the Natural Killer T Cell Agonist Alpha-Galactosylceramide Enhances Protective Immunity to Limit Pulmonary and Extra-Pulmonary Bacterial Burden in Mice

    Directory of Open Access Journals (Sweden)

    Arshad Khan

    2017-12-01

    Full Text Available Infection by Mycobacterium tuberculosis (Mtb remains a major global concern and the available Bacillus Calmette-Guerin (BCG vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer, a potent natural killer T (NKT cell agonist. Vaccinated animals exhibited strong antigen-specific CD4 and CD8 T cells responses in the spleen, cervical lymph nodes and lungs. In general, inclusion of the α-GalCer adjuvant significantly enhanced these responses that persisted over 50 days. Furthermore, aerosolized Mtb infection of vaccinated mice resulted in a significant reduction of bacterial load of the lungs and spleens as compared to levels seen in naïve controls or those vaccinated with subunit proteins, adjuvant , or BCG alone. The protection induced by the Mtb antigens and-GalCer vaccine through sublingual route correlated with a TH1-type immunity mediated by antigen-specific IFN-γ and IL-2 producing T cells.

  19. Acceptability and feasibility of the use of 400 μg of sublingual misoprostol after mifepristone for medical abortion up to 63 days since the last menstrual period: evidence from Uzbekistan.

    Science.gov (United States)

    Raghavan, Sheila; Tsereteli, Tamar; Kamilov, Asamidin; Kurbanbekova, Dilfuza; Yusupov, Dilmurod; Kasimova, Feruza; Jymagylova, Dilbar; Winikoff, Beverly

    2013-04-01

    To examine the efficacy, acceptability and feasibility of early medical abortion, with the option of home administration of misoprostol, in Uzbekistan. A total of 450 women were enrolled at national, municipal and private facilities in Tashkent, Uzbekistan. Women who presented for termination of pregnancy with gestations up to 63 days were recruited to participate in the study. All eligible pregnant women who consented to participate swallowed a 200 mg mifepristone pill in the clinic and were given the option of taking 400 μg misoprostol sublingually either at the clinic or at home 24-48 hours after mifepristone administration. Abortion status was determined two weeks later. Almost all women (99.5%) chose home administration of misoprostol. The sublingual route of misoprostol administration was acceptable or very acceptable to 89% of participants. Ninety-five percent of women had complete abortions after mifepristone and misoprostol. Almost all participants preferred a medical abortion to surgery for a future procedure (95%). Mifepristone medical abortion with home administration of misoprostol is an acceptable and feasible option for women in Uzbekistan. The method worked well at all three facility types.

  20. Isotretinoin Oil-Based Capsule Formulation Optimization

    Science.gov (United States)

    Tsai, Pi-Ju; Huang, Chi-Te; Lee, Chen-Chou; Li, Chi-Lin; Huang, Yaw-Bin; Tsai, Yi-Hung; Wu, Pao-Chu

    2013-01-01

    The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X 1), hydrogenated coconut oil (X 2), and soybean oil (X 3). The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM). Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X 1 X 2, X 1 X 3, and X 2 X 3) showed more potential influence than that of the main factors (X 1, X 2, and X 3). An optimal predicted formulation with Y 10 min, Y 30 min, Y 60 min, and Y 90 min release values of 12.3%, 36.7%, 73.6%, and 92.7% at X 1, X 2, and X 3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f 2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile. PMID:24068886

  1. Stagnation -point flows with stretching surfaces: A unified formulation and new results

    OpenAIRE

    Weidman, P; Turner, MR

    2016-01-01

    A unified formulation for stagnation-point flows and linearly stretching plates is given wherein the two can occur separately or in unison. Reductions to known cases are given. It is noticed that previous work on stretching plates beneath planar and axisymmetric stagnation point flows have respectively aligned planar stretching and axisymmetric stretching. The general formulation reveals other combinations of stretching beneath stagnation-point flows exist and three new cases are studied in d...

  2. Formulation of heat absorbing glasses

    Directory of Open Access Journals (Sweden)

    Álvarez-Casariego, Pedro

    1996-06-01

    Full Text Available In the thermal exchanges between buildings and environment, glazing is an element of major importance, for it largely influences the so-called Solar Heat Gain and Thermal Losses. These parameters can be modified by applying different type of coatings onto glass surface or by adding colorant compounds during glass melting. The latter is a cheaper way to control the Solar Heat Gain. The knowledge of the laws governing the interaction between colorant compounds and solar radiation, allows us to define glass formulations achieving specific aesthetic requirements and solar energy absorption. In this paper two examples of application of the modelling of glass colorants spectral absorptance are presented. First is addressed to obtaining a glass with high luminous transmittance and low solar energy transmittance, and the other one to obtaining a glass with neutral colour appearance and minimized solar energy transmittance. Calculation formulas are defined together with photometric properties so-obtained. These type of glasses are particularly suitable to be used as building and automotive glazing, for they retain the mechanical characteristics and possibilities of transformation of standard glass.

    En los intercambios de energía entre un edificio y el medio exterior, el vidrio es el elemento de mayor importancia, por su influencia en la Ganancia de Calor Solar y en las Pérdidas Térmicas. Estos parámetros pueden ser modificados mediante el depósito de capas sobre el vidrio o mediante la adición de compuestos absorbentes de la radiación solar. Esta última vía es la más económica para controlar la Ganancia de Calor Solar. El conocimiento de las leyes que gobiernan la interacción de los diversos colorantes con la radiación solar, permite definir formulaciones de vidrios con características especificas de tipo estético y de absorción energética. En este trabajo se presentan dos ejemplos de aplicación de esta modelización de las

  3. Decontamination formulations for disinfection and sterilization

    Science.gov (United States)

    Tucker, Mark D.; Engler, Daniel E.

    2007-09-18

    Aqueous decontamination formulations that neutralize biological pathogens for disinfection and sterilization applications. Examples of suitable applications include disinfection of food processing equipment, disinfection of areas containing livestock, mold remediation, sterilization of medical instruments and direct disinfection of food surfaces, such as beef carcasses. The formulations include at least one reactive compound, bleaching activator, inorganic base, and water. The formulations can be packaged as a two-part kit system, and can have a pH value in the range of 7-8.

  4. Novel formulation for enhancing efficiency of metribuzin.

    Science.gov (United States)

    Karakotov, S D; Zheltova, E V; Putsykin, Yu G; Balakin, K V; Shapovalov, A A

    2006-01-01

    The biological efficiency of systemic herbicide metribuzin in water dispersible granules (WG) and solution colloid concentrate (SCC) formulations was studied in field experiments. Metribuzin formulation in SCC state was prepared by the addition of a mixture of anionic and non-ionic surfactants and alkoxylated sorbitan esters as specific adjuvants. The ability of herbicide formulation containing Metribuzin in SCC state to provide increases in control of broadleaf and grassy weeds in comparison to WG was observed. The possibility to reduce application rate of Metribuzin from high-dose to low-dose without losing efficacy of weed control was demonstrated.

  5. Understanding Pesticide Risks: Toxicity and Formulation

    OpenAIRE

    Muntz, Helen; Miller, Rhonda; Alston, Diane

    2016-01-01

    This fact sheet provides information about pesticide risks to human health, primary means of pesticide exposure, standardized measures of pesticide toxicity, pesticide signal words and type of pesticide formulations.

  6. Paclitaxel Albumin-stabilized Nanoparticle Formulation

    Science.gov (United States)

    This page contains brief information about paclitaxel albumin-stabilized nanoparticle formulation and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  7. Chemicals-Based Formulation Design: Virtual Experimentations

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    2011-01-01

    This paper presents a systematic procedure for virtual experimentations related to the design of liquid formulated products. All the experiments that need to be performed when designing a liquid formulated product (lotion), such as ingredients selection and testing, solubility tests, property mea...... on the design of an insect repellent lotion will show that the software is an essential instrument in decision making, and that it reduces time and resources since experimental efforts can be focused on one or few product alternatives.......This paper presents a systematic procedure for virtual experimentations related to the design of liquid formulated products. All the experiments that need to be performed when designing a liquid formulated product (lotion), such as ingredients selection and testing, solubility tests, property...... measurements, can now be performed through the virtual Product-Process Design laboratory [[1], [2] and [3

  8. Formulation and Characterization of Biodegradable Medicated ...

    African Journals Online (AJOL)

    Formulation and Characterization of Biodegradable Medicated Chewing Gum Delivery System for Motion Sickness using Corn Zein as Gum Former. ... Journal Home > Vol 14, No 5 (2015) >. Log in or Register to get access to full text ...

  9. Formulation and characterization of caffeine biodegradable chewing ...

    African Journals Online (AJOL)

    Formulation and characterization of caffeine biodegradable chewing gum delivery system for alertness using plasticized poly (D,L-lactic acid) as gum base. ... Tropical Journal of Pharmaceutical Research. Journal Home · ABOUT · Advanced ...

  10. Algebraic formulation of higher gauge theory

    Science.gov (United States)

    Zucchini, Roberto

    2017-06-01

    In this paper, we present a purely algebraic formulation of higher gauge theory and gauged sigma models based on the abstract theory of graded commutative algebras and their morphisms. The formulation incorporates naturally Becchi - Rouet -Stora - Tyutin (BRST) symmetry and is also suitable for Alexandrov - Kontsevich - Schwartz-Zaboronsky (AKSZ) type constructions. It is also shown that for a full-fledged Batalin-Vilkovisky formulation including ghost degrees of freedom, higher gauge and gauged sigma model fields must be viewed as internal smooth functions on the shifted tangent bundle of a space-time manifold valued in a shifted L∞-algebroid encoding symmetry. The relationship to other formulations where the L∞-algebroid arises from a higher Lie groupoid by Lie differentiation is highlighted.

  11. Concepts and formulations for spatial multibody dynamics

    CERN Document Server

    Flores, Paulo

    2015-01-01

    This book will be particularly useful to those interested in multibody simulation (MBS) and the formulation for the dynamics of spatial multibody systems. The main types of coordinates that can be used in the formulation of the equations of motion of constrained multibody systems are described. The multibody system, made of interconnected bodies that undergo large displacements and rotations, is fully defined. Readers will discover how Cartesian coordinates and Euler parameters are utilized and are the supporting structure for all methodologies and dynamic analysis, developed within the multibody systems methodologies. The work also covers the constraint equations associated with the basic kinematic joints, as well as those related to the constraints between two vectors. The formulation of multibody systems adopted here uses the generalized coordinates and the Newton-Euler approach to derive the equations of motion. This formulation results in the establishment of a mixed set of differential and algebraic equ...

  12. Efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet for the treatment of adults with opioid dependence: A randomized trial.

    Science.gov (United States)

    Webster, Lynn; Hjelmström, Peter; Sumner, Michael; Gunderson, Erik W

    2016-01-01

    This prospective, randomized, active-controlled, non-inferiority study evaluated the efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet (Zubsolv ® ; buprenorphine/naloxone rapidly dissolving tablet) versus generic buprenorphine for induction of opioid maintenance among dependent adults. The study, conducted at 13 sites from June 2013 to January 2014, included a 2-day blinded induction phase and a 27-day open-label stabilization/maintenance phase. During the blinded induction, patients received fixed doses of buprenorphine/naloxone rapidly dissolving tablets or generic buprenorphine. During open-label stabilization/early maintenance, all patients received buprenorphine/naloxone rapidly dissolving tablets. The primary efficacy assessment was treatment retention at day 3; buprenorphine/naloxone rapidly dissolving tablets were considered non-inferior to generic buprenorphine if the lower limit of the 95% confidence interval for the difference between the treatments was ≥-10% in patients retained on day 3. Secondary assessments included opioid withdrawal symptoms and cravings as measured using the Clinical Opiate Withdrawal Scale, the Subjective Opiate Withdrawal Scale, and the opioid cravings visual analogue scale. Safety was also assessed. A total of 313 patients were randomly assigned to induction with generic buprenorphine or buprenorphine/naloxone rapidly dissolving tablets. The mean age was 38.4 years, and the mean duration of opioid dependence was 12.4 years. For the primary efficacy assessment, 235 of 256 patients (91.8%) were retained at day 3 and continued to the maintenance phase. The lower limit of the 95% confidence interval was -13.7; thus, buprenorphine/naloxone rapidly dissolving tablets did not demonstrate non-inferiority to generic buprenorphine, and significantly more patients who received induction with generic buprenorphine (122/128 [95.3%]) were retained at day 3 compared with those who received induction with

  13. Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case-control study on 171 patients. The EFESO-children multicenter trial.

    Science.gov (United States)

    Acquistapace, Franca; Agostinis, Fabio; Castella, Vincenzo; Kantar, Ahmad; Novembre, Elio; Perrone, Maria Rosaria; Pietrasanta, Michele; Sambugaro, Renato; Milani, Massimo

    2009-11-01

    Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in 'real life' in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case-control study to evaluate the effect of SLIT in children (age 6-18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case-control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone ALK-Abellò). Controls (n = 81) were defined as sex-age- and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean +/- SD) was 4.5 +/- 2.5 in cases and 9.0 +/- 3.0 in controls (-50%) (p = 0.0001). MS (mean +/- SD) was 2.5 +/- 1.9 and 3.6 +/- 2.1 in the case and control groups, respectively (-31%) (p = 0.0001). At the end of

  14. Ferrous iron content of intravenous iron formulations

    OpenAIRE

    Gupta, Ajay; Pratt, Raymond D; Crumbliss, Alvin L.

    2016-01-01

    The observed biological differences in safety and efficacy of intravenous (IV) iron formulations are attributable to physicochemical differences. In addition to differences in carbohydrate shell, polarographic signatures due to ferric iron [Fe(III)] and ferrous iron [Fe(II)] differ among IV iron formulations. Intravenous iron contains Fe(II) and releases labile iron in the circulation. Fe(II) generates toxic free radicals and reactive oxygen species and binds to bacterial siderophores and oth...

  15. Combinatorial formulation of Ising model revisited

    OpenAIRE

    Costa G.A.T.F.da; Maciel A. L.

    2003-01-01

    In 1952, Kac and Ward developed a combinatorial formulation for the two dimensional Ising model which is another method of obtaining Onsager's famous formula for the free energy per site in the termodynamic limit of the model. Feynman gave an important contribution to this formulation conjecturing a crucial mathematical relation which completed Kac and Ward ideas. In this paper, the method of Kac, Ward and Feynman for the free field Ising model in two dimensions is reviewed in a selfcontained...

  16. FORMULATION AND EVALUATION OF MEDICATED ANALGESIC STICKS

    OpenAIRE

    Nagalakshmi.R*, Surinder Kaur

    2017-01-01

    The main objective of this research was to formulate an analgesic drug incorporated in topically used sticks, prepared using suitable ointment bases with varied concentrations of waxes, lubricants, surfactants, etc. and incorporation of medicament in the optimized formula by heating and congealing process. Indomethacin was the drug of choice used because; this drug if used orally has a lot of side effects which has to be reduced. The main purpose of this formulation was to dispense medicated ...

  17. Project Integration Architecture: Formulation of Semantic Parameters

    Science.gov (United States)

    Jones, William Henry

    2005-01-01

    One of several key elements of the Project Integration Architecture (PIA) is the intention to formulate parameter objects which convey meaningful semantic information. In so doing, it is expected that a level of automation can be achieved in the consumption of information content by PIA-consuming clients outside the programmatic boundary of a presenting PIA-wrapped application. This paper discusses the steps that have been recently taken in formulating such semantically-meaningful parameters.

  18. Preformulation and Formulation Investigational New Drugs

    Science.gov (United States)

    1990-07-01

    the formulation excipients (i.e., hydrou lactose , NF, colloidal silicon dioxide, NF, absolute ethyl alcohol, USP) according to compendial...Strategy 1 Excipients Employed 2 Tablet Preparation 3 Dissolution Test 3 Results 3 Conclusions 15 Recommendations 15 PRODUCTION OF EXTENDED RELEASE...Povidone@, Plasdoneg or KollidonO) and other excipients . Extended release over 6-12 hours was desired from such formulations. Release characteristics

  19. The Boltzmann equation in the difference formulation

    Energy Technology Data Exchange (ETDEWEB)

    Szoke, Abraham [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brooks III, Eugene D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-05-06

    First we recall the assumptions that are needed for the validity of the Boltzmann equation and for the validity of the compressible Euler equations. We then present the difference formulation of these equations and make a connection with the time-honored Chapman - Enskog expansion. We discuss the hydrodynamic limit and calculate the thermal conductivity of a monatomic gas, using a simplified approximation for the collision term. Our formulation is more consistent and simpler than the traditional derivation.

  20. Design of novel urogenital pharmabiotic formulations containing lactobacilli, salivaricin CRL 1328 and non-microbial compounds with different functionalities.

    Science.gov (United States)

    Vera Pingitore, Esteban; Juárez Tomás, María Silvina; Wiese, Birgitt; Nader-Macías, María Elena Fátima

    2015-06-01

    The administration of pharmabiotics is a promising alternative to antimicrobial drugs for the treatment and/or prevention of female urogenital infections. To design pharmabiotic formulations including bioactive ingredients of microbial origin combined with non-microbial substances and then to evaluate the stability of the combinations during freeze-drying and storage. Different formulations including Lactobacillus gasseri CRL 1263, Lactobacillus salivarius CRL 1328, salivaricin CRL 1328 (a bacteriocin) and non-microbial compounds (lactose, inulin and ascorbic acid) were assayed, and the ingredients were freeze-dried together or separately. The formulations were stored in gelatin capsules at 4 °C for 360 d. The viability of lactobacilli was affected to different extents depending on the strains and on the formulations assayed. L. salivarius and ascorbic acid were successfully combined only after the freeze-drying process. Salivaricin activity was not detected in formulations containing L. gasseri. However, when combined with ascorbic acid, lactose, inulin or L. salivarius, the bacteriocin maintained its activity for 360 d. The selected microorganisms proved to be compatible for their inclusion in multi-strain formulations together with lactose, inulin and ascorbic acid. Salivaricin could be included only in a L. salivarius CRL 1328 single-strain formulation together with non-microbial substances. This study provides new insights into the design of urogenital pharmabiotics combining beneficial lactobacilli, salivaricin CRL 1328 and compounds with different functionalities.

  1. An herbal formulation for hemorrhoids treatment

    Directory of Open Access Journals (Sweden)

    S. Dehdari

    2017-11-01

    Full Text Available Background and objectives: Hemorrhoids is the most painful rectal disease. Straining and pregnancy seem playing chief roles in the development of hemorrhoids. Symptoms of hemorrhoids may include bleeding, inflammation and pain. Despite current medical efforts, many discomforts of hemorrhoids have not been handled. The aim of the present study was to formulate and evaluate Itrifal-e muqil (IM tablet to achieve desired pharmaceutical properties. Method: Quality control tests of Allium ampeloperasum L, Commiphora mukul (Hook. ex Stocks Engl., Phyllanthus emblica L., Terminalia chebula Retz. and Terminalia bellerica Retz. were performed. Afterwards, different formulations were prepared and their physical properties were evaluated. Subsequently, the formulation was coated and its physicochemical characteristics were assessed. Result: All of the herbs demonstrated good results in quality control tests according to United State Pharmacopeia (USP. Formulation-1 that was completely prepared based on explained manufacturing process of IM in traditional medicine manuscripts did not show suitable pharmaceutical properties. Among different formulations, Formulation-3 that consisted of A. ampeloperasum, C. mukul, P. emblica, T. chebula and T. bellerica, displayed best outcomes through different tests. Conclusion: Modern pharmaceutical approaches can excellently be adapted for IM preparations.

  2. The coevent formulation of quantum theory

    Science.gov (United States)

    Wallden, Petros

    2013-06-01

    Understanding quantum theory has been a subject of debate from its birth. Many different formulations and interpretations have been proposed. Here we examine a recent novel formulation, namely the coevents formulation. It is a histories formulation and has as starting point the Feynman path integral and the decoherence functional. The new ontology turns out to be that of a coarse-grained history. We start with a quantum measure defined on the space of histories, and the existence of zero covers rules out single-history as potential reality (the Kochen Specker theorem casted in histories form is a special case of a zero cover). We see that allowing coarse-grained histories as potential realities avoids the previous paradoxes, maintains deductive non-contextual logic (alas non-Boolean) and gives rise to a unique classical domain. Moreover, we can recover the probabilistic predictions of quantum theory with the use of the Cournot's principle. This formulation, being both a realist formulation and based on histories, is well suited conceptually for the purposes of quantum gravity and cosmology.

  3. Bioequivalence study of two fluconazole capsule formulations in healthy volunteers.

    Science.gov (United States)

    Pereira, R; Fidelis, S; Vanunci, M L P; Oliveira, C H; Mendes, G D; Abib, E; Moreno, R A

    2004-01-01

    To compare the bioavailability of a fluconazole 150 mg capsule formulation from Laboratório Teuto Brasileiro Ltd., Brazil (test formulation), and Zoltec 150 mg capsule from Laboratórios Pfizer Ltd., Brazil (reference formulation), in 24 volunteers of both sexes. The study was conducted open with randomized 2-period crossover design and a 2-week washout period. Plasma samples were obtained over a 168-hour interval. Fluconazole concentrations were analyzed by combined reversed-phase liquid chromatography and tandem mass spectrometry (LC/MS/MS) with positive ion electrospray ionization using selected ion monitoring method. From the fluconazole plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-inf) and C(max). Geometric mean of fluconazole/Zoltec 150 mg individual percent ratio was 102.6% for AUC(last), 102.2% for AUC(0-inf) and 109.4% for C(max). The 90% confidence intervals were 97.3-108.2%, 97.0-107.8%, and 103.1-116.0%, respectively. Since the 90% CI for both Cmax, AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that fluconazole 150 mg capsule was bioequivalent to Zoltec 150 mg, according to both the rate and extent of absorption.