WorldWideScience

Sample records for sublingual zolpidem tartrate

  1. 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.

  2. 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.

  3. Forced Oxidative degradation study of Zolpidem tartrate by HPLC ...

    African Journals Online (AJOL)

    indicating assay method developed for the determination of zolpidem in the presence of its degradation products. Zolpidem was refluxed with 6% peroxide at 60°C for 48 hrs with constant stirring. The method was developed and optimized by ...

  4. 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

  5. Development and Validation of a Stability-Indicating Capillary Electrophoresis Method for the Determination of Zolpidem Tartrate in Tablet Dosage Form with Positive Confirmation using 2D- and 3D-DAD Fingerprints.

    Science.gov (United States)

    Al Azzam, Khaldun M; Yit, Lee Kam; Saad, Bahruddin; Shaibah, Hassan

    2014-01-01

    The aim of the current study was to develop a simple, precise, and accurate capillary zone electrophoresis method for the determination of zolpidem tartrate in tablet dosage form. Separation was conducted in normal polarity mode at 25°C, 22 kV, using hydrodynamic injection for 10 s. Separation was achieved using a background electrolyte of 20 mM disodium hydrogen phosphate adjusted with phosphoric acid (85%), pH at 5.50, and detection at 254 nm. Using the above optimized conditions, complete determination took place in less than 3 min using amiloride HCl as the internal standard. The method was linear over the range of 3-1000 μg mL(-1) with a correlation coefficient of 0.9999. Forced degradation studies were conducted by introducing a sample of zolpidem tartrate standard and pharmaceutical sample solutions to different forced degradation conditions, being neutral (water), basic (0.1 M NaOH), acidic (0.1 M HCl), oxidative (10% H2O2), temperature (60°C in oven for 3 days), and photolytic (exposure to UV light at 254 nm for 2 h). Degradation products resulting from the stress studies did not interfere with the detection of zolpidem tartrate and the assay can be considered stability-indicating.

  6. Reversal of Zolpidem Intoxication By Sublingual Flumazenil

    Science.gov (United States)

    2008-11-01

    pregnancy test immediately prior to each experimental session. One subject was dropped from the analyses due to presenting with Lasik surgery two days prior...benzodiazepine antagonism by flumazenil and aminophylline. Pharmacotherapy , 16(6), 1166-1172. Caldwell JL, Prazinko BF, Rowe T, et al. (2003). Improving

  7. Zolpidem induced delirium

    Directory of Open Access Journals (Sweden)

    Sameeran S Chate

    2013-01-01

    Full Text Available Use of non-benzodiazepine hypnotics like zolpidem for insomnia has become a popular practice because of better safety profile and low abuse potential. However, neuropsychiatric side-effects such as headache, depression, memory deficits and abnormal dreams with zolpidem use have been reported. Delirum is a rare side-effect associated with zolpidem use. Here, we report a case of delirium, which occurred with a single dose of zolpidem. Clinicians prescribing zolpidem for insomnia should look into the risk factors/pre-disposing factors such as old age, female gender, substance abuse/dependence, systemic infections, psychiatric illness and multiple drug interactions. It is recommended to stick to the lowest dose possible whenever indicated.

  8. Zolpidem for the Treatment of Neurologic Disorders: A Systematic Review.

    Science.gov (United States)

    Bomalaski, Martin N; Claflin, Edward S; Townsend, Whitney; Peterson, Mark D

    2017-09-01

    Given its selective action on the ω1 subtype of the γ-aminobutyric acid A receptor, zolpidem tartrate presents a potential treatment mechanism for other neurologic disorders. To synthesize studies that used zolpidem to treat neurologic disorders. Eligibility criteria included any published English-language article that examined the use of zolpidem for noninsomnia neurologic disorders in humans for all dates up to March 20, 2015. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. Publication bias was mitigated by searching clinicaltrials.gov for unpublished studies. Two rounds of screening were performed based on title and then abstract, and coding was performed by 2 coders. All methods followed the PRISMA Reporting Guidelines for systematic reviews of the literature. The initial search produced 2314 articles after removing duplicates. After exclusion based on a review of abstracts, 67 articles remained for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions, including stroke, traumatic brain injury, encephalopathy, and dementia. Study designs included case reports (n = 28), case series (n = 8), single-patient interventional (n = 13), pretest and posttest (n = 9), randomized clinical trials (n = 9), and crossover studies (n = 5). Only 11 studies had more than 10 participants. Effects of zolpidem were wide ranging (eg, improvement on the JFK Coma Recovery Scale-Revised, the Unified Parkinson Disease Rating Scale, and the Burke-Fahn-Marsden Dystonia Rating Scale) and generally lasted 1 to 4 hours before the participant returned to baseline. Sedation was the most common adverse effect. Zolpidem has been observed to transiently treat a large variety of neurologic disorders, most often related to movement disorders and disorders of consciousness. Much of what

  9. Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

    Science.gov (United States)

    Rush, C R; Baker, R W; Rowlett, J K

    2000-02-01

    Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5-15.0 mg), triazolam (0.0625-0.3750 mg), pentobarbital (25-150 mg), caffeine (100-600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines.

  10. Fentanyl Sublingual Spray

    Science.gov (United States)

    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 ( ...

  11. Zolpidem

    Science.gov (United States)

    ... any other sleeping pill.tell your doctor what herbal products you are taking, especially St. John's wort.tell your doctor if you drink or have ever drunk large amounts of alcohol, use or have ever used street drugs, or have overused prescription medications. Also tell ...

  12. Zolpidem dependence, abuse and withdrawal: A case report

    Science.gov (United States)

    Heydari, Mostafa; Isfeedvajani, Mohsen Saberi

    2013-01-01

    Zolpidem, a nonbenzodiazepine hypnotic, binds to the benzodiazepine binding site on the gamma-aminobutyric acid type A (GABA-A) receptors. Many studies have reported efficacy and safety of zolpidem in treatment of insomnia, low abuse, and dependence capability. However, many cases of zolpidem abuse and dependence were reported around the world. This case showed that zolpidem can exert abuse capability, euphoric mood, tolerance, and withdrawal syndrome. PMID:24520235

  13. Zolpidem dependence, abuse and withdrawal: A case report

    Directory of Open Access Journals (Sweden)

    Mostafa Heydari

    2013-01-01

    Full Text Available Zolpidem, a nonbenzodiazepine hypnotic, binds to the benzodiazepine binding site on the gamma-aminobutyric acid type A (GABA-A receptors. Many studies have reported efficacy and safety of zolpidem in treatment of insomnia, low abuse, and dependence capability. However, many cases of zolpidem abuse and dependence were reported around the world. This case showed that zolpidem can exert abuse capability, euphoric mood, tolerance, and withdrawal syndrome.

  14. 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...

  15. Evidence for zolpidem efficacy in brain damage | Clauss | South ...

    African Journals Online (AJOL)

    Previous reports have shown that zolpidem could reverse semi-coma and improve cerebral perfusion after brain injury. Studies in animals have implicated omega 1 GABAergic action as reason for this improvement. Evidence for the efficacy of zolpidem in a wide range of brain pathology is reviewed here and the mechanism ...

  16. Zolpidem Overdose: A Medical and Ethical Dilemma.

    Science.gov (United States)

    Shuaib, Waqas; Beatrice, Cristina; Abazid, Ahmad G

    Acute altered mental status can be caused by a broad range of etiologies, including cerebrovascular, neurologic, traumatic, metabolic, infectious, psychiatric, medications, etc. We present a case of a 53-year-old healthcare professional with an acute altered mental status after a trip to Africa. The patient was extensively worked up for infectious, cardiovascular, and neurologic etiologies, and all results were within normal limits. Further history revealed an overdose of a self-medicated hypnotic (zolpidem) for insomnia. The patient was conservatively managed and discharged on trazadone for insomnia.

  17. Daytime sleep and performance following a zolpidem and melatonin cocktail.

    Science.gov (United States)

    Wesensten, Nancy Jo; Balkin, Thomas J; Reichardt, Rebecca M; Kautz, Mary A; Saviolakis, George A; Belenky, Gregory

    2005-01-01

    Pharmacologic enhancement of daytime sleep may help sustain optimal cognitive performance. At effective doses, zolpidem induces sleep but also impairs performance. Combining melatonin with low-dose zolpidem may promote daytime sleep without exacerbating performance impairments seen with high-dose zolpidem alone. Following an 8-hour undisturbed nighttime sleep period, 80 subjects (50 men, 30 women) were administered oral zolpidem 0, 5, 10, or 20 mg at 10:00 am (n = 20 per group) and then oral melatonin 0 or 5 mg at 10:30 am (thus, n = 10 per drug combination) in a double-blind randomized fashion. Subjects napped from 10:00 am to 11:30 am, at which time they were awakened and cognitive tests administered (Restricted Reminding, Paired-Associates, and Psychomotor Vigilance). A second nap ensued from 12:45 pm to 4:00 pm, followed immediately by further testing. Melatonin 5 mg plus zolpidem 0 mg enhanced daytime sleep (P .05). Zolpidem 20 mg plus melatonin 0 mg also enhanced daytime sleep (albeit nonsignificantly), but memory and vigilance were impaired (P sleep-promoting effects were not evident until the second nap. No advantages to administering melatonin plus zolpidem "cocktails" were evident. Unlike zolpidem, melatonin 5 mg alone improved daytime sleep without impairing memory and vigilance. Functional coupling of sleep-inducing and memory-impairing effects may be specific to benzodiazepine-receptor agonists such as zolpidem, suggesting potential advantages to using melatonin in the operational environment. That melatonin's sleep-promoting effects were delayed for several hours presents a practical consideration that may limit melatonin's usefulness when daytime sleep periods cannot be reliably anticipated or planned in advance.

  18. Extraordinary arousal from semi-comatose state on zolpidem ...

    African Journals Online (AJOL)

    propylene amine oxime (99mTc HMPAO) brain single photon emission computed tomography (SPECf) before and after administration of the gamma-aminobutyric acid (GABA) agonist zolpidem. It was observed that 15 minutes after application ...

  19. Insomnia: clinical experience with zolpidem (sanval

    Directory of Open Access Journals (Sweden)

    Yakov Iosifovich Levin

    2010-01-01

    Full Text Available The paper describes the present view of the problem of insomnia and gives a classification of sleep disorders and basic methods for their drug and non-drug therapy. Emphasis is placed on the role of the objective sleep study - polysomnography. The use of the current hypnotics belonging to a three Zs group and the minimization of administration of benzodiazepines are most important in pharmacotherapy for insomnia. The results of a clinical polysomnographic study of the effect of Zolpidem (Sanval in patients with insomnia are presented. The subjective evaluation of the beneficial effect of a 10-day course of Sanval is confirmed by the objective studies of the sleep pattern undergoing positive changes in the most important indicators, such as the process of falling asleep, the time of intrasleep awakenings, and the duration of Δ-sleep. The high safety and good tolerability of Sanval permit the latter to be assessed as an effective agent for the treatment of insomnia.

  20. Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature

    Science.gov (United States)

    Miyaoka, Tsuyoshi; Tsuji, Seiichi; Inami, Yasushi; Nishida, Akira; Horiguchi, Jun

    2010-01-01

    Objective: Zolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject. Data Sources: Articles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions. Study Selection and Data Extraction: Publications relevant to the objective of this article were obtained (1992–2010), and some adverse neuropsychiatric reactions were summarized. Data Synthesis: Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men; (2) zolpidem dose: the adverse reactions that develop are dose dependent; (3) protein binding affinity: a high proportion of zolpidem is protein bound; therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions; and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem. Conclusions: Zolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex

  1. Dystonic Dysarthria in Wilson Disease: Efficacy of Zolpidem

    Directory of Open Access Journals (Sweden)

    Aurélia Poujois

    2017-10-01

    Full Text Available Wilson disease (WD is a rare genetic disorder characterized by copper overload in the liver and the brain. Neurological presentations are mainly related to the accumulation of copper in the basal ganglia, the brainstem, and the cerebellum. Dysarthria is a frequent symptom, with dystonic, spastic, or parkinsonian components and is usually resistant to medical or voice rehabilitation therapies. Here, we report the case of a patient with WD diagnosed at the age of 12, who presented a severe and constant dysarthria from dystonic origin which was unresponsive to benzodiazepines and anticholinergic drugs. When she was 25-year-old, she tried zolpidem at bedtime for sleeping difficulties and reported a paradoxical effect of this drug on her voice. To confirm the effect of zolpidem on her dystonic dysarthria, we realized a full evaluation of her dysarthria at baseline without zolpidem and after 4 days of treatment by 10 mg twice a day. Lexical access was evaluated by the semantic fluency; dysarthria by the Intelligibility Score, the spontaneous speech and reading rates, the maximum phonation time on the sustained vowel [a] and by a perceptive evaluation. Two hours after the intake of zolpidem, improvement of all the parameters tested, with the exception of the maximum phonation time, was observed. Semantic fluency increased by 59%, the spontaneous speech rate by 88% and the reading rate by 76%. General dystonia remained unchanged and the tolerance of zolpidem was satisfactory. Since then, the patient takes zolpidem 5 mg five times a day, and 4 years later shows persistent improvement in oral communication and a good drug tolerance. In this single-case study, we showed that regular daytime intake of zolpidem could have a persisting effect on a complex dystonic dysarthria that was resistant to usual medical treatments.

  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. Zolpidem Administration and Risk of Hepatocellular Carcinoma: A Case-Control Study in Taiwan

    Directory of Open Access Journals (Sweden)

    Shih-Wei Lai

    2017-10-01

    Full Text Available Background/Objectives: Previous studies showed that zolpidem use could be associated with increased cancer risk, but the role of zolpidem on hepatocellular carcinoma (HCC risk remains undetermined. The study purpose was to examine the association between HCC risk and zolpidem use in Taiwan.Methods: Using the database from the Taiwan National Health Insurance Program, we designed a case-control study which consisted of 77986 subjects aged 20 years or older with newly diagnosed HCC as the case group, and 77986 subjects without HCC as the control group, from 2000 to 2011. Ever use of zolpidem was defined as a subject who had at least a prescription for zolpidem before the index date. Never use was defined as a subject who did not have a prescription for zolpidem before the index date. The association between HCC risk and zolpidem use was determined by the odds ratio (OR and 95% confidence interval (CI in a multivariable logistic regression model.Results: After adjustment for confounding factors, the adjusted OR of HCC was 1.05 (95% CI 0.97, 1.13 for subjects with ever use of zolpidem, compared with never use of zolpidem. The adjusted OR of HCC was 1.01 for subjects with increasing cumulative duration of zolpidem use for every 1 year (95% CI 0.99, 1.03, compared with never use of zolpidem.Conclusion: There is no significant association between HCC risk and zolpidem use. There is no duration-dependent effect of zolpidem use on HCC risk.

  4. Clinical Applications of Sublingual Immunotherapy.

    Science.gov (United States)

    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.

  5. Dielectric and thermal studies on gel grown strontium tartrate ...

    Indian Academy of Sciences (India)

    /fulltext/boms/033/04/0377-0382. Keywords. Permittivity; polarization effects; strontium tartrate; thermal properties; dielectric properties. Abstract. Results of dielectric and thermal studies on strontium tartrate pentahydrate crystals are described.

  6. Zolpidem-induced sleepwalking, sleep related eating disorder, and sleep-driving: fluorine-18-flourodeoxyglucose positron emission tomography analysis, and a literature review of other unexpected clinical effects of zolpidem.

    Science.gov (United States)

    Hoque, Romy; Chesson, Andrew L

    2009-10-15

    Zolpidem is a hypnotic which acts at the GABAA receptor and is indicated for short-term insomnia. Sleep related disorders including somnambulism, sleep related eating and sleep-driving have been reported with zolpidem. A 51-year-old insomniac who used zolpidem 10 mg nightly starting at 44 years of age is described. A few weeks after starting zolpidem she began walking, eating, and had one episode of driving while asleep. Episodes of sleep related eating, sleepwalking, and sleeptalking occurred 3 nights per week, 1 to 2 h after sleep onset. After her evaluation, the patient's zolpidem was gradually discontinued, and all sleep related activities immediately ceased. An 18F-FDG-PET was obtained 2 months after discontinuation of zolpidem. The following day, FDG was administered 1 h after oral administration of 10 mg zolpidem, and then a second PET was performed. We report the results and a review of the literature regarding other unintended effects seen with zolpidem use.

  7. 21 CFR 558.360 - Morantel tartrate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Morantel tartrate. 558.360 Section 558.360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... control of mature gastrointestinal nematode infections of cattle including stomach worms (Haemonchus spp...

  8. Analysis of zolpidem in postmortem fluids and tissues using ultra-performance liquid chromatography-mass spectrometry.

    Science.gov (United States)

    2014-02-01

    Zolpidem is a nonbenzodiazepine sedative hypnotic drug used for the short-term treatment of insomnia. Its : use is common and wide-spread. While quite effective in producing sedation, zolpidem has potentially : hazardous side effects when put in the ...

  9. [Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

    Science.gov (United States)

    Liu, Ping; He, Xinrong; Guo, Mei

    2010-04-01

    To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P Calculus Bovis group was higher than combination group (P Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

  10. 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

  11. 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...

  12. Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

    National Research Council Canada - National Science Library

    Xia, Binfeng; Yang, Zhen; Zhou, Haiying; Lukacova, Viera; Zhu, Wei; Milewski, Mikolaj; Kesisoglou, Filippos

    2015-01-01

    ...™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo...

  13. 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.

  14. 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....

  15. 21 CFR 520.2045 - Pyrantel tartrate powder; pyrantel tartrate pellets.

    Science.gov (United States)

    2010-04-01

    ... roundworms (Parascaris). (ii) It is administered as a single dose at 0.57 gram of pyrantel tartrate per 100... be slaughtered for food purposes. (2) Swine: (i) For the removal and control of large roundworms...., Triodontophorus), pinworms (Oxyuris), and large roundworms (Parascaris). (ii) It is administered as a single dose...

  16. 21 CFR 520.1450 - Morantel tartrate oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Morantel tartrate oral dosage forms. 520.1450... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1450 Morantel tartrate oral dosage forms. ...

  17. 21 CFR 184.1077 - Potassium acid tartrate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium acid tartrate. 184.1077 Section 184.1077... Listing of Specific Substances Affirmed as GRAS § 184.1077 Potassium acid tartrate. (a) Potassium acid... accordance with § 184.1(b)(1), the ingredient is used in food with no limitation other than current good...

  18. Growth features of ammonium hydrogen d-tartrate single crystals

    Indian Academy of Sciences (India)

    Unknown

    Growth features of ammonium hydrogen d-tartrate single crystals. G SAJEEVKUMAR*, R RAVEENDRAN, ... Ammonium hydrogen d-tartrate (d-AHT) single crystals were grown in silica gel. The growth fea- tures of these .... tables 1 and 2 summarize the results of the experiments car- ried out. The tables indicate that with a ...

  19. 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...

  20. Postoperative Sleep Disturbances after Zolpidem Treatment in Fast-Track Hip and Knee Replacement

    DEFF Research Database (Denmark)

    Krenk, Lene; Jennum, Poul; Kehlet, Henrik

    2014-01-01

    arousals (p = 0.004). Levels of pain and opioid use were similar in the 2 groups. CONCLUSIONS: Our objective data did not support the primary hypothesis that one night's treatment with zolpidem would significantly improve sleep architecture following...... major surgery, although there was improved feeling of sleep quality and fatigue associated with fewer postoperative arousals. CITATION: Krenk L; Jennum P; Kehlet H. Postoperative sleep disturbances after zolpidem treatment in fast-track hip and knee replacement....

  1. Síndrome de ingesta nocturna como efecto colateral del zolpidem Sleep related eating disorders as a side effect of zolpidem

    Directory of Open Access Journals (Sweden)

    Stella Maris Valiensi

    2010-06-01

    Full Text Available El zolpidem es una droga hipnótica utilizada para el tratamiento del insomnio. Disminuye la latencia del sueño, el número total de despertares y aumenta el tiempo total del sueño respetando en general su arquitectura. Se cree que aumenta la fase 3 del sueño lento profundo. Nuestro objetivo es comunicar 8 casos de síndrome de ingesta nocturna relacionado al sueño y conductas automáticas complejas asociadas a sonambulismo como efecto colateral del zolpidem. Se analizaron las historias clínicas de 8 pacientes tratados con zolpidem que referían ingesta nocturna de alimentos con amnesia total o parcial del episodio. Se presentan 6 mujeres y 2 hombres, entre 32 y 72 años (media: 58 años, 7 tratados con zolpidem 10 mg/noche y 1 con zolpidem 12.5 mg/noche de liberación prolongada. El tiempo de exposición previo al desarrollo de eventos fue de 1 a 180 días (media de 39.8. El número de episodios relatados era de 1 a 8/noche (media 2.5 asociado con amnesia. Los episodios desaparecieron por completo en el 100% de los casos al suspender la medicación. El síndrome de ingesta nocturna relacionado al sueño es una parasomnia de sueño lento profundo que consiste en episodios de ingesta de alimento o bebida durante la noche, con amnesia parcial o completa del episodio. El zolpidem podría inducir el síndrome de ingesta nocturna relacionado al sueño en aproximadamente el 1% de pacientes, aunque creemos que es un efecto adverso que está subdiagnosticado. Se resuelve simplemente suspendiendo la medicación.Zolpidem is a hypnotic drug used in sleep disorders. It binds selectively to alpha 1 subunit of the GABA A benzodiazepine receptor. Zolpidem reduces sleep latency, number of arousals and increases the total time of sleep. However, it is considered that it may increase phase 3 of non rapid eye movement sleep, where somnambulism can take place. Our aim is to report 8 cases of sleep related eating disorders associated with the use of this drug

  2. The incidence of Zolpidem use in suspected DUI drivers in Miami-Dade Florida: a comparative study using immunalysis Zolpidem ELISA KIT and gas chromatography-mass spectrometry screening.

    Science.gov (United States)

    Reidy, L; Gennaro, W; Steele, B W; Walls, H C

    2008-10-01

    In 1993, Zolpidem (Ambien), a non-benzodiazepine hypnotic agent, was approved for use in the United States for the short-term treatment of insomnia. Zolpidem has a rapid onset of action and short elimination half-life, rendering it ideal as a sleep aid. The objective of this study was to evaluate, and retrospectively compare, the use of the Immunalysis ELISA kit and gas chromatograpy-mass spectrometry (GC-MS) to screen blood/urine specimens for zolpidem. In addition, results for the incidence of zolpidem in suspected DUI drivers in 2007 are compared to previous years' data. The ELISA kit was evaluated for cross-reactivity with zaleplon and zopiclone and zolpidem metabolite I. Urine samples (n = 100) and blood samples (n = 100) were selected from specimens received into the DUI laboratory in 2007 and were screened via the Immunalysis Zolpidem ELISA kit and on GC-MS in full EI scan mode following an alkaline liquid-liquid extraction. Results show 5% of the urine and blood samples screened positive for zolpidem using the ELISA kits, and all 5% confirmed positive for zolpidem using GC-MS. The ELISA kit demonstrated no cross-reactivity to zaleplon or zopiclone at a spiked urine concentration of 1000 ng/mL. Ten cases of suspected DUI drivers in 2007 confirmed positive for zolpidem by ELISA and GC-MS in blood/urine, a higher incidence rate than in the previous years. Because of the low percentage elimination of the parent compound in urine, a screening method for the detection of the main metabolite of zolpidem may be needed for better detection of drug impairment driving due to zolpidem.

  3. 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.

  4. Effect of zolpidem on miniature IPSCs and occupancy of postsynaptic GABAA receptors in central synapses.

    Science.gov (United States)

    Perrais, D; Ropert, N

    1999-01-15

    GABAA-mediated miniature IPSCs (mIPSCs) were recorded from layer V pyramidal neurons of the visual cortex using whole-cell patch-clamp recording in rat brain slices. At room temperature, the benzodiazepine site agonist zolpidem enhanced both the amplitude (to 138 +/- 26% of control value at 10 microM) and the duration (163 +/- 14%) of mIPSCs. The enhancement of mIPSC amplitude was not caused by an increase of the single-channel conductance of the postsynaptic receptors, as determined by peak-scaled non-stationary fluctuation analysis of mIPSCs. The effect of zolpidem on fast, synaptic-like (1 msec duration) applications of GABA to outside-out patches was also investigated. The EC50 for fast GABA applications was 310 microM. In patches, zolpidem enhanced the amplitude of currents elicited by subsaturating GABA applications (100-300 microM) but not by saturating applications (10 mM). The increase of mIPSC amplitude by zolpidem provides evidence that the GABAA receptors are not saturated during miniature synaptic transmission in the recorded cells. By comparing the facilitation induced by 1 microM zolpidem on outside-out patches and mIPSCs, we estimated the concentration of GABA seen by the postsynaptic GABAA receptors to be approximately 300 microM after single vesicle release. We have estimated a similar degree of receptor occupancy at room and physiological temperature. However, at 35 degreesC, zolpidem did not enhance the amplitude of mIPSCs or of subsaturating GABA applications on patches, implying that, in these neurons, zolpidem cannot be used to probe the degree of receptor occupancy at physiological temperature.

  5. Doctor Shopping Behavior for Zolpidem Among Insomnia Patients in Taiwan: A Nationwide Population-Based Study.

    Science.gov (United States)

    Lu, Tzu-Hsuan; Lee, Yen-Ying; Lee, Hsin-Chien; Lin, You-Meei

    2015-07-01

    Although zolpidem is listed as a controlled drug in Taiwan, patients' behavior has not been restricted and has led to the problem of doctor shopping behavior (DSB), leading to overutilization of medical resources and excess spending. The National Health Insurance Administration in Taiwan has instituted a new policy to regulate physicians' prescribing behavior and decrease DSB. This retrospective study aimed to analyze the DSB for zolpidem by insomnia patients and assess related factors. Data were extracted from the Longitudinal Health Insurance Database in Taiwan. Individuals with a diagnosis of insomnia who received more than one prescription of zolpidem in 2008 were followed for 24 mo. Doctor shopping was defined as ≥ 2 prescriptions by different doctors within ≥ 1 day overlapping in the duration of therapy. The percentage of zolpidem obtained through doctor shopping was used as an indicator of the DSB of each patient. Among the 6,947 insomnia patients who were prescribed zolpidem, 1,652 exhibited DSB (23.78%). The average dose of zolpidem dispensed for each patient during 24 mo was 244.21 daily defined doses. The doctor shopping indicator (DSI) was 0.20 (standard deviation, 0.23) among patients with DSB. Younger age, chronic diseases, high number of diseases, higher premium status, high socioeconomic status, and fewer people served per practicing physicians were all factors significantly related to doctor shopping behavior. Doctor shopping for zolpidem appears to be an important issue in Taiwan. Implementing a proper referral system with efficient data exchange by physician or pharmacist-led medication reconciliation process might reduce DSB. © 2015 Associated Professional Sleep Societies, LLC.

  6. Desensitization of GABAergic receptors as a mechanism of zolpidem-induced somnambulism.

    Science.gov (United States)

    Juszczak, Grzegorz R

    2011-08-01

    Sleepwalking is a frequently reported side effect of zolpidem which is a short-acting hypnotic drug potentiating activity of GABA(A) receptors. Paradoxically, the most commonly used medications for somnambulism are benzodiazepines, especially clonazepam, which also potentiate activity of GABA(A) receptors. It is proposed that zolpidem-induced sleepwalking can be explained by the desensitization of GABAergic receptors located on serotonergic neurons. According to the proposed model, the delay between desensitization of GABA receptors and a compensatory decrease in serotonin release constitutes the time window for parasomnias. The occurrence of sleepwalking depends on individual differences in receptor desensitization, autoregulation of serotonin release and drug pharmacokinetics. The proposed mechanism of interaction between GABAergic and serotonergic systems can be also relevant for zolpidem abuse and zolpidem-induced hallucinations. It is therefore suggested that special care should be taken when zolpidem is used in patients taking at the same time selective serotonin reuptake inhibitors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. The effect of zolpidem on sleep quality, stress status, and nondipping hypertension.

    Science.gov (United States)

    Huang, Yuli; Mai, Weiyi; Cai, Xiaoyan; Hu, Yunzhao; Song, Yuanbin; Qiu, Ruofeng; Wu, Yanxian; Kuang, Jian

    2012-03-01

    Poor sleep quality and stress status have previously been shown to be closely associated with higher activation of the sympathetic nervous system and to be independent predictors of nondipping hypertension. This study aimed to evaluate the effects of the non-hypotensive sedative zolpidem on sleep quality, stress status, and nondipping hypertension. A total of 103 nondippers were defined as poor or good sleepers by the Pittsburgh Sleep Quality Index. They were randomized to receive zolpidem or placebo treatment for 30 days. Stress status was assessed by the Perceived Stress Scale, and levels of epinephrine and norepinephrine were examined to investigate the underlying mechanisms. Poor sleepers treated with zolpidem for 30 days showed significant improvements in sleep quality and stress levels (Psleep quality and stress status, and can convert nondippers with poor sleep quality into dippers. It may be an option for treating nondipping hypertensive patients with poor sleep quality. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. In vitro and in vivo evaluation of nano-based films for buccal delivery of zolpidem

    Directory of Open Access Journals (Sweden)

    Bandar Essa AL-DHUBIAB

    Full Text Available Abstract Insomnia is becoming increasingly prevalent in the world general population. Therapies used by patients include over-the-counter therapies, herbal and dietary supplements, and pharmacological or nonpharmacological treatments. Among these, zolpidem is a pharmacological treatment popularly used for insomnia. Zolpidem is well tolerated and especially efficacious for initiation of sleep, and therefore is effective for the treatment of sleep-onset insomnia. The purpose of the present study was to design and evaluate zolpidem nanoparticle-impregnated buccal films to prolong the duration of its action. Zolpidem nanospheres were prepared by double emulsion solvent evaporation and then loaded into buccoadhesive films (Z1-Z4 comprised of different concentrations of HPMC K100, Eudragit® RL 100, and carbopol 974P. The prepared films were characterized for physicomechanical properties, mucoadhesion, percent hydration, in vitro drug release, ex vivo permeation, and in vivo studies. In vitro drug release was found to depend upon film composition. Ex vivo studies showed that film Z4 had the highest flux. In vivo studies revealed that administration of zolpidem nanosphere-impregnated film enhanced absorption of the drug (p < 0.0001, with a higher peak plasma concentration (52.54 ± 8.22 ng/mL and area under the curve from time 0 to α (236.00 ± 39.51 ng.h/mL than oral administration. The increase in time taken to reach the maximum drug concentration (1.5 h further signifies the potential of these films to provide prolonged drug release. Given these promising results, we concluded that these buccal films could be an alternative route for effective zolpidem delivery.

  9. Síndrome de ingesta nocturna como efecto colateral del zolpidem

    Directory of Open Access Journals (Sweden)

    Stella Maris Valiensi

    2010-06-01

    Full Text Available El zolpidem es una droga hipnótica utilizada para el tratamiento del insomnio. Disminuye la latencia del sueño, el número total de despertares y aumenta el tiempo total del sueño respetando en general su arquitectura. Se cree que aumenta la fase 3 del sueño lento profundo. Nuestro objetivo es comunicar 8 casos de síndrome de ingesta nocturna relacionado al sueño y conductas automáticas complejas asociadas a sonambulismo como efecto colateral del zolpidem. Se analizaron las historias clínicas de 8 pacientes tratados con zolpidem que referían ingesta nocturna de alimentos con amnesia total o parcial del episodio. Se presentan 6 mujeres y 2 hombres, entre 32 y 72 años (media: 58 años, 7 tratados con zolpidem 10 mg/noche y 1 con zolpidem 12.5 mg/noche de liberación prolongada. El tiempo de exposición previo al desarrollo de eventos fue de 1 a 180 días (media de 39.8. El número de episodios relatados era de 1 a 8/noche (media 2.5 asociado con amnesia. Los episodios desaparecieron por completo en el 100% de los casos al suspender la medicación. El síndrome de ingesta nocturna relacionado al sueño es una parasomnia de sueño lento profundo que consiste en episodios de ingesta de alimento o bebida durante la noche, con amnesia parcial o completa del episodio. El zolpidem podría inducir el síndrome de ingesta nocturna relacionado al sueño en aproximadamente el 1% de pacientes, aunque creemos que es un efecto adverso que está subdiagnosticado. Se resuelve simplemente suspendiendo la medicación.

  10. 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.

  11. TESTING THE EFFECTS OF THE IMIDAZOPYRIDINE ZOLPIDEM ON MEMORY : AN ECOLOGICALLY VALID APPROACH

    NARCIS (Netherlands)

    Jackson, JL; Louwerens, JW; Cnossen, F; de Jong, HTP

    1992-01-01

    The present study explores whether memory impairments are found on the morning following intake of the hypnotic zolpidem which is a member of a new pharmaceutical class, the imidazopyridines. The procedure used is novel: it involves testing subjects in their own homes via the telephone. A previous

  12. The effects of repeated zolpidem treatment on tolerance, withdrawal-like symptoms, and GABAA receptor mRNAs profile expression in mice: comparison with diazepam.

    Science.gov (United States)

    Wright, Brittany T; Gluszek, Catherine F; Heldt, Scott A

    2014-08-01

    Zolpidem is a short-acting, non-benzodiazepine hypnotic that acts as a full agonist at α1-containing GABAA receptors. Overall, zolpidem purportedly has fewer instances of abuse and dependence than traditionally used benzodiazepines. However, several studies have shown that zolpidem may be more similar to benzodiazepines in terms of behavioral tolerance and withdrawal symptoms. In the current study, we examined whether subchronic zolpidem or diazepam administration produced deficits in zolpidem's locomotor-impairing effects, anxiety-like behaviors, and changes in GABAAR subunit messenger RNA (mRNA). Mice were given subchronic injections of either zolpidem (10 mg/kg), diazepam (20 mg/kg), or vehicle twice daily for 7 days. On day 8, mice were given a challenge dose of zolpidem (2 mg/kg) or vehicle before open field testing. Another set of mice underwent the same injection regimen but were sacrificed on day 8 for qRT-PCR analysis. We found that subchronic zolpidem and diazepam administration produced deficits in the acute locomotor-impairing effects of zolpidem and increased anxiety-like behaviors 1 day after drug termination. In addition, we found that subchronic treatment of zolpidem and diazepam induced distinct but overlapping GABAAR subunit mRNA changes in the cortex but few changes in the hippocampus, amygdala, or prefrontal cortex. Levels of mRNA measured in separate mice after a single injection of either zolpidem or diazepam revealed no mRNA changes. In mice, subchronic treatment of zolpidem and diazepam can produce deficits in the locomotor-impairing effects of zolpidem, anxiety-like withdrawal symptoms, and subunit-specific mRNA changes.

  13. 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...

  14. 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.

  15. 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....

  16. 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

  17. 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...

  18. Comparison of actigraphy and polysomnography to assess effects of zolpidem in a clinical research unit.

    Science.gov (United States)

    Peterson, Barry T; Chiao, Ping; Pickering, Eve; Freeman, Jon; Zammit, Gary K; Ding, Yu; Badura, Lori L

    2012-04-01

    This study sought to compare devices that use actigraphy for measuring sleep endpoints in the clinical research unit (CRU) and home environment. The abilities of polysomnography (PSG) and actigraphy monitors to detect drug effects in a CRU were also investigated. Eleven healthy subjects were recruited and monitored with PSG for four consecutive nights in a CRU after receiving no treatment (night 1, N1), and then placebo or 5 mg day(-1) or 10 mg day(-1) zolpidem in a randomised, cross-over design. Subjects wore two devices that use actigraphy (a Respironics® Actiwatch® on the wrist and a BodyMedia® Sensewear® Armband on the upper-arm) on the non-dominant arm for five nights at home and four nights in the CRU during PSG. Wake after sleep onset (WASO) and total sleep time (TST) measured by PSG and estimates of WASO by the Actiwatch decreased significantly with 5mg but not 10mg of zolpidem versus placebo. Direct activity (counts/min) with the Actiwatch decreased in response to zolpidem (both 5 and 10 mg day(-1)) versus placebo. Armband recordings of direct activity were similar to the Actiwatch but not significantly different versus placebo. Both actigraphy device estimates of TST were approximately 1h longer in CRU versus home. Agreement between actigraphy estimates of TST and WASO and PSG values of TST and WASO were closer during nights with zolpidem treatment. PSG can detect the effects of zolpidem on sleep in a CRU setting. Actigraphy can provide useful assessment of sleep, but direct activity endpoints may be more effective than estimates of TST and WASO. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. 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.

  20. [Hypotensive effect of three different formulations of brimonidine tartrate in normal eyes].

    Science.gov (United States)

    Abud, Tulio Batista; Scuoteguazza Filho, Marcio; Oliveira, Edjane Souza Santos; Abud, Jorge Felipe; Prata Junior, João Antonio

    2013-01-01

    To compare the hypotensive effect in normal eyes of three formulations with different concentrations of brimonidine tartrate: 0.2%; 0.15% and 0.1%. Prospective, randomized, double-blind study included 60 volunteers, who underwent initial ophthalmologic examination and measurement of intraocular pressure (IOP). Individuals were divided into three groups: (1) brimonidine tartrate 0.15%, (2) brimonidine tartrate 0.2% and (3) brimonidine tartrate 0.1% and randomly received one drop each of drops in each eye. The IOP was measured after 30 minutes, 1 hour and 2 hours. We found that all concentrations of brimonidine tartrate significantly reduced intraocular pressure during the study period, with pbrimonidine.

  1. Arformoterol Tartrate: A Review of Pharmacology, Analysis and ...

    African Journals Online (AJOL)

    Erah

    This article is a review of the therapeutic significance of arformoterol tartrate, a new generation β2 adrenergic agonist bronchodilator available in a nebulized form. Arformoterol is well absorbed through the lungs when administered via a standard jet nebulizer and is useful in long-term maintenance therapy.

  2. Arformoterol Tartrate: A Review of Pharmacology, Analysis and ...

    African Journals Online (AJOL)

    This article is a review of the therapeutic significance of arformoterol tartrate, a new generation 2 adrenergic agonist bronchodilator available in a nebulized form. Arformoterol is well absorbed through the lungs when administered via a standard jet nebulizer and is useful in long-term maintenance therapy of ...

  3. On the growth of calcium tartrate tetrahydrate single crystals

    Indian Academy of Sciences (India)

    Unknown

    tartaric acid content of the gel is completely exhausted partly through the formation of calcium tartrate crystals and partly through the demonstrable loss of tartaric acid to the solution at the top in the gel region close to the super- natant liquid. Normally, many small crystals grow in the gel medium and only a few of them are ...

  4. Thermal behaviour of strontium tartrate single crystals grown in gel

    Indian Academy of Sciences (India)

    Unknown

    reflected petrological microscope. Hence the crystallinity is observed under a stereo binocular microscope (Carl. Zeiss) and confirmed as single crystal. In order to study the effect of dopants on the morpho- logy and growth of strontium tartrate (SrT), 10% (W/V) solution of lead nitrate was also mixed with the top solu- tion.

  5. Growth features of ammonium hydrogen d-tartrate single crystals

    Indian Academy of Sciences (India)

    Ammonium hydrogen -tartrate (-AHT) single crystals were grown in silica gel. The growth features of these crystals with variation of parameters like specific gravity of the gel, gel pH, acid concentrations, concentration of the feed solution and gel age were studied in detail.

  6. 21 CFR 520.1450a - Morantel tartrate bolus.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Morantel tartrate bolus. 520.1450a Section 520.1450a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... control of mature gastrointestinal nematode infections of cattle including stomach worms (Haemonchus spp...

  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. Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large scale calcium imaging study with miniaturized fluorescence microscope.

    Directory of Open Access Journals (Sweden)

    Tamara Berdyyeva

    Full Text Available Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65% significantly decreasing the rate of calcium transients, and a small subset (3% showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

  9. Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large scale calcium imaging study with miniaturized fluorescence microscope.

    Science.gov (United States)

    Berdyyeva, Tamara; Otte, Stephani; Aluisio, Leah; Ziv, Yaniv; Burns, Laurie D; Dugovic, Christine; Yun, Sujin; Ghosh, Kunal K; Schnitzer, Mark J; Lovenberg, Timothy; Bonaventure, Pascal

    2014-01-01

    Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65%) significantly decreasing the rate of calcium transients, and a small subset (3%) showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

  10. Using benzodiazepine detoxification and cognitive behavioral psychotherapy in the treatment of a patient with generalized anxiety disorder comorbid with high-dose zolpidem dependence

    Directory of Open Access Journals (Sweden)

    Shen-Hua Lu

    2016-01-01

    Full Text Available In recent years, literature has shown that zolpidem dependence is not uncommon in the clinical practice, but there is no standard guideline for treatment of zolpidem dependence. Benzodiazepine detoxification has been widely used for alcohol detoxification, which is also an inhibitory substance. We would like to share the experience of benzodiazepine detoxification and cognitive behavioral psychotherapy in a patient with high-dose zolpidem dependence comorbid with generalized anxiety disorder.

  11. 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...

  12. 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.

  13. Fluorimetric quantification of brimonidine tartrate in eye drops.

    Science.gov (United States)

    Sunitha, G; Bhagirath, R; Alapati, V R; Ramakrishna, K; Subrahmanyam, C V S; Anumolu, P D

    2013-11-01

    A simple and sensitive spectrofluorimetric method has been developed for the estimation of brimonidine tartrate in pure and eye drops. Linearity was obeyed in the range of 0.2-3.0 ΅g/ml in dimethyl formamide as solvent at an emission wavelength (λem) of 530 nm after excitation wavelength (λex) of 389 nm with good correlation coefficient of 0.998. The limit of detection and limit of quantification for this method were 22.0 and 72.0 ng/ml, respectively. The developed method was statistically validated as per International Conference on Harmonisation guidelines. The percentage relative standard deviation values were found to be less than 2 for accuracy and precision studies. The results obtained were in good agreement with the labelled amounts of the marketed formulations. The proposed method was effectively applied to routine quality control analysis of brimonidine tartrate in their eye drops.

  14. Tolerância ao fenômeno alucinatório induzido pelo zolpidem: relato de caso Tolerancia al fenómeno alucinatorio inducido por el zolpidem: relato de caso Tolerance to zolpidem-induced hallucinations: case report

    Directory of Open Access Journals (Sweden)

    Saint-Clair Bahls

    2005-12-01

    Full Text Available INTRODUÇÃO: O hipnótico zolpidem é considerado efetivo e seguro, entretanto, existem na literatura alguns relatos de caso de fenômeno alucinatório associado ao seu uso. Relataremos mais um caso de alucinações induzidas pelo zolpidem em paciente jovem do sexo feminino. DISCUSSÃO: Este caso, segundo nosso conhecimento, é o primeiro descrito na literatura que sugere a possibilidade de ocorrer, em alguns pacientes, o desenvolvimento de tolerância a esse efeito alucinatório adverso raro, porém, importante. Apresentamos uma discussão sobre algumas hipóteses farmacocinéticas e farmacodinâmicas deste fenômeno. CONCLUSÕES: Alertamos para a necessidade de atenção ao fato da indução alucinatória pelo zolpidem e sua tolerância, assim como a importância de seu melhor entendimento.INTRODUCTION: El hipnótico zolpidem es considerado efectivo y seguro. Sin embargo, hay en la literatura algunos relatos de caso de fenómeno alucinatorio asociado a su uso. Relataremos un caso más sobre alucinaciones inducidas por zolpidem en una paciente joven de sexo femenino. DISCUSIÓN: Este caso, según nuestro conocimiento, es el primero descrito en la literatura que sugiere la posibilidad de que en algunos pacientes ocurra el desarrollo de tolerancia a este efecto alucinatorio, adverso y raro, sin embargo, importante. Presentamos una discusión sobre algunas hipótesis farmacocinéticas y farmacodinámicas de este fenómeno. CONCLUSION: Por la necesidad de atención, alertamos al hecho de la inducción alucinatoria relacionada al zolpidem y a su tolerancia, así como a la importancia de comprenderla mejor.BACKGROUND: Zolpidem is reported to be a safe and effective hypnotic agent. In the literature, there are some case reports of hallucinations after zolpidem administration. We report one more case in witch zolpidem lead to hallucinations in young adult female. DISCUSSION: This case, to our knowledge, is the first to suggest the possibility of

  15. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic.

    Science.gov (United States)

    Desager, J P; Hulhoven, R; Harvengt, C; Hermann, P; Guillet, P; Thiercelin, J F

    1988-01-01

    The combined use of a hypnotic and a neuroleptic is a rather frequent situation, encountered especially in the psychiatric sphere. We therefore tested zolpidem and chlorpromazine in six healthy subjects by using a double-blind latin square design. All of them received single doses of 20 mg zolpidem (ZOL), 50 mg chlorpromazine (CPZ) and the combination of ZOL + CPZ. The medication was given as a single dose in the morning and each treatment being separated by a 1-week interval. Zolpidem produced moderate to severe sedation varying according to the subjects. Psychometric performances (manual dexterity, Stroop test), alertness and psychomotricity (visual analogue scales) were reduced up to 3 h after drug intake. Chlorpromazine alone did not have much effect. Combined administration of ZOL and CPZ was rather more effective than ZOL alone. The pharmacokinetics of ZOL or CPZ remained unchanged except for the elimination half-life of CPZ, which increased significantly when administered along with ZOL. No other pharmacodynamic or pharmacokinetic interaction between ZOL and CPZ was evident. The fact that the ZOL and CPZ combination accentuated the pharmacodynamical effects can be explained to result from the summation of each of their own pharmacological effect.

  16. Characterization of pure and copper-doped iron tartrate crystals ...

    Indian Academy of Sciences (India)

    Single crystal growth of pure and copper-doped iron tartrate crystals bearing composition Cu Fe(1−) C4H4O6 · H2O, where = 0, 0.07, 0.06, 0.05, 0.04, 0.03, is achieved using gel technique. The elemental analysis has been done using energy-dispersive X-ray analysis (EDAX) spectrum. The characterization studies ...

  17. Effects of eszopiclone and zolpidem on sleep-wake behavior, anxiety-like behavior and contextual memory in rats

    Science.gov (United States)

    Huang, Max P.; Radadia, Kushan; Macone, Brian W.; Auerbach, Sanford H.; Datta, Subimal

    2010-01-01

    At present, eszopiclone and zolpidem are the most commonly prescribed drugs for treating insomnia. Despite the established relationship between sleep disturbance and anxiety, it remains unknown whether targeted treatment for insomnia may affect acute anxiety. Therefore, the objective of this study was to examine the effects of three different doses (1, 3, and 10 mg/kg) of eszopiclone and zolpidem on the states of sleep and wakefulness, levels of anxiety-like behavior, and long-term contextual memory in footshock-induced anxious rats. The results of this study demonstrated that the administration of eszopiclone and zolpidem both were equally effective in attenuating footshock stressor-induced suppression of slow-wave sleep (SWS). The administration of eszopiclone at 1 mg/kg or zolpidem at 1 and 3 mg/kg doses showed a tendency for attenuating stressor-induced suppression of REM sleep. However, the REM sleep attenuating effects of these drugs disappeared when they were administered at higher doses. The administration of eszopiclone at 3 and 10 mg/kg doses and zolpidem at all three doses reduced the power of electroencephalographic theta band frequencies during wakefulness. In addition, the administration of eszopiclone at 1 and 3 mg/kg doses suppressed stressor-induced anxiety-like behavior. The administration of zolpidem at 1, 3, or 10 mg/kg doses was not effective in attenuating stressor-induced anxiety-like behavior. Contextual memory after administration of eszopiclone at 1 mg/kg dose had no effects, but was reduced significantly with increased dosage. Contextual memory after administration of zolpidem, at all three doses, was severely disrupted. The results of this study suggest that eszopiclone at a low dose could be used effectively to control anxiety and anxiety-induced insomnia. PMID:20153782

  18. Changes in prescribing and healthcare resource utilization after FDA Drug Safety Communications involving zolpidem-containing medications.

    Science.gov (United States)

    Kesselheim, Aaron S; Donneyong, Macarius; Dal Pan, Gerald J; Zhou, Esther H; Avorn, Jerry; Schneeweiss, Sebastian; Seeger, John D

    2017-06-01

    Products containing the sedative/hypnotic zolpidem were subject to Drug Safety Communications (DSCs) in January and May 2013 describing the risk of next-morning impairment and recommending lower starting doses particularly for women. This study aimed to assess whether zolpidem DSCs were associated with prescribing-pattern changes between January 2011 and December 2013. We assessed overall dispensings of zolpidem-containing products between January 2011 and December 2013 by conducting a time-series analysis. Analyses were stratified by gender because the DSC contained gender-specific information. Participants were patients drawn from the Optum Clinformatics data source of commercially insured people in the USA. We evaluated changes in mean prescribed dose of the two drugs and health care utilization metrics. Each month of the study, more than 80 000 patients received a zolpidem-containing product and approximately one-tenth as many received eszopiclone. The two DSCs did not affect the downward trajectory of new zolpidem prescriptions. However, there was an increase in use of lower-dose forms of zolpidem (30% increase, p < 0.001), coupled with a reduction in higher-dose forms (13% decrease, p = 0.03), so that the average dose decreased after the DSCs (from 9.7 mg to 9.4 mg, p < 0.001), a change that was not seen with eszopiclone (from 2.74 mg to 2.74 mg, p = 0.45). The DSCs related to zolpidem-containing products shifted prescribing toward the lower-dose formulations, consistent with the recommendations in the DSCs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  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. Influence of zolpidem and sleep inertia on balance and cognition during nighttime awakening: a randomized placebo-controlled trial.

    Science.gov (United States)

    Frey, Danielle J; Ortega, Justus D; Wiseman, Courtney; Farley, Claire T; Wright, Kenneth P

    2011-01-01

    To determine whether sleep inertia (grogginess upon awakening from sleep) with or without zolpidem impairs walking stability and cognition during awakenings from sleep. Three within-subject conditions hypnotic medication (zolpidem), placebo (sleep inertia), and wakefulness control randomized using balanced Latin square design. Sleep laboratory. Twelve older and 13 younger healthy adults. Five milligrams of zolpidem or placebo 10 minutes before scheduled sleep (double-blind: zolpidem or sleep inertia); placebo before sitting in bed awake for 2 hours after their habitual bedtime (single-blind: wakefulness control). Tandem walk on a beam and cognition, measured using computerized performance tasks, approximately 120 minutes after treatment. No participants stepped off the beam on 10 practice trials. Seven of 12 older adults stepped off the beam after taking zolpidem, compared with none after sleep inertia and three after wakefulness control. Fewer young adults stepped off the beam: three after taking zolpidem, one after sleep inertia, and none after wakefulness control. Number needed to harm analyses showed one tandem walk failure for every 1.7 (95% confidence interval (CI)=1.4-2.0) older and 5.5 (95% CI=5.2-5.8) younger adults treated with zolpidem. Cognition was significantly more impaired after zolpidem exposure than with wakefulness control in older and younger participants (working memory: older, -4.3 calculations, 95% CI=-7.0 to -1.7; younger, -12.4 calculations, 95% CI=-18.2 to -6.7; Stroop: older, 76-ms increase (95% CI=13.5-138.4 ms); younger, 126-ms increase, 95% CI=34.7-217.5 ms), whereas sleep inertia significantly impaired cognition in younger but not older participants. Zolpidem produced clinically significant balance and cognitive impairments upon awakening from sleep. Because impaired tandem walk predicts falls and hip fractures and because impaired cognition has important safety implications, use of nonbenzodiazepine hypnotic medications may have

  1. Formulation and evaluation of sublingual tablets of losartan potassium

    Directory of Open Access Journals (Sweden)

    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. 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.

  3. 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.

  4. 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, ...

  5. 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.

  6. 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.

  7. 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.

  8. Effect of Zolpidem on Sleep Quality of Professional Firefighters; a Double Blind, Randomized, Placebo-Controlled Crossover Clinical Trial

    Directory of Open Access Journals (Sweden)

    Ramin Mehrdad

    2015-10-01

    Full Text Available Professional firefighting is among the most demanding jobs. Prior studies have showed the notable prevalence of poor sleep quality among professional firefighters that may result in catastrophes. The aim of this study was in field confirmation of zolpidem usage (10 mg/PO/bed time for short term management of poor sleeps quality among professional firefighters. In a double-blind, randomized, placebo-controlled crossover clinical trial among professional firefighters, 27 poor sleepers were assigned randomly to one of the two groups. Two 14 days experimental periods were separated by a 14-day washout phase. Sleep quality was assessed using the Persian version of Pittsburgh Sleep Quality Index (PSQI. Six of the 27 enrolled voluntaries dropped out. Two rare side effects of zolpidem occurred in the study. A significant improvement of the PSQI score was detected in zolpidem period versus placebo in both groups (7.14 ± 3.02 vs 12.38 ± 2.51, PP=0.89. Zolpidem significantly improved all components of PSQI (Subjective sleep quality, Sleep latency, Sleep duration, Habitual sleep efficiency, Sleep disturbances and Daytime dysfunction in the current study except the use of sleep medication. Sleep onset latency was the component of PSQI with the greatest degree of abnormality among firefighters in a previous study. Interestingly, sleep latency was the component of PSQI with the most treatment effect of zolpidem in the current study. Zolpidem can be used as a part of treatment regimens in short time management of poor sleep quality among professional firefighters.

  9. Quality of Life in Primary Insomnia: Three-week Treatment With Zolpidem Vs. Lorazepam

    Directory of Open Access Journals (Sweden)

    Janjic Vladimir

    2017-10-01

    Full Text Available Insomnia is a condition of inadequate quality or quantity of sleep that has extremely adverse effects on daytime activities. Th e aim of this study was to compare the quality of life in patients with primary insomnia before and after a 3-week treatment with lorazepam (n=20 and zolpidem (n=21 and to compare the potential differences in dysfunctional beliefs and attitudes regarding patients’ sleep between the two groups. Th e diagnosis of primary insomnia was established using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and patients had to complete a specially designed sleep log every day; on scheduled visits, we also administered a Visual Analogue Scale for quality of life and a self-evaluation questionnaire about Dysfunctional Beliefs and Attitudes related to Sleep at the beginning and end of this study. In summary, the examinees in our study had significantly decreased parameters of quality of life, quite lower than expected based on previous findings in this area. However, by the end of the study, quality of life significantly improved with treatment: it improved by approximately 2/3 in the Lorazepam group and more than twice in the Zolpidem group, with a significant difference in favour of Zolpidem (p=0.047. Th is finding is most likely a consequence of its better safety profile and in part its better efficiency in terms of influence on certain domains of sleep itself, as previously discussed. Further specialized studies in this area with larger samples and a more detailed methodology are clearly warranted.

  10. 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.

  11. 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.

  12. Amantadine, apomorphine and zolpidem in the treatment of disorders of consciousness.

    Science.gov (United States)

    Gosseries, Olivia; Charland-Verville, Vanessa; Thonnard, Marie; Bodart, Olivier; Laureys, Steven; Demertzi, Athena

    2014-01-01

    Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to improve arousal levels and recovery of consciousness. We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes of the patients' neurological status, leading sometimes to dramatic improvements. These findings are discussed in the context of current hypotheses of these agents' therapeutic mechanisms on cerebral function. In order to improve our understanding of the underlying pathophysiological mechanisms of these drugs, we suggest combining sensitive and specific behavioral tools with neuroimaging and electrophysiological measures in large randomized, double-blind, placebo-controlled experimental designs. We conclude that the pharmacokinetics and pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration to determine which treatment would provide a better neurological outcome regarding the patient's etiology, diagnosis, time since injury and overall condition.

  13. Trial of Zolpidem, Eszopiclone, and Other GABA Agonists in a Patient with Progressive Supranuclear Palsy

    Directory of Open Access Journals (Sweden)

    Andrew Young Chang

    2014-01-01

    Full Text Available Progressive supranuclear palsy (PSP is a progressive, debilitating neurodegenerative disease of the Parkinson-plus family of syndromes. Unfortunately, there are no pharmacologic treatments for this condition, as most sufferers of the classic variant respond poorly to Parkinson medications such as levodopa. Zolpidem, a gamma aminobutyric acid (GABA agonist specific to the α-1 receptor subtype, has been reported to show improvements in symptoms of PSP patients, including motor dysfunction, dysarthria, and ocular disturbances. We observed a 73-year-old woman with a six-year history of PSP, who, upon administration of a single 12.5 mg dose of sustained-release zolpidem, exhibited marked enhancements in speech, facial expressions, and fine motor skills for five hours. These results were reproduced upon subsequent clinic visits. In an effort to find a sustainable medication that maximized these beneficial effects while minimizing side effects and addressing some of her comorbid neuropsychological conditions, a trial of five other GABA receptor agonists was performed with the patient’s consent, while she and her caregivers were blinded to the specific medications. She and her caretakers subsequently reported improvements, especially visual, while on eszopiclone, and, to a lesser degree, temazepam and flurazepam.

  14. 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.

  15. 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.

  16. Differential effects of midazolam and zolpidem on sleep-wake states and epileptic activity in WAG/Rij rats

    NARCIS (Netherlands)

    Depoortere, H.; Francon, D.; Luijtelaar, E.L.J.M. van; Drinkenburg, W.H.I.M.; Coenen, A.M.L.

    1995-01-01

    Hypnotic drugs are known to possess antiepileptic activity. Therefore, the effects of the benzodiazepine hypnotic midazolam (10 mg/kg) and the novel imidazopyridine hypnotic zolpidem (10 mg/kg) on sleep-wake states and on the number of spike-wave discharges were evaluated in WAG/Rij rats. Rats of

  17. Effect of escitalopram combined with zolpidem on sleep structure, sleep process and neurotransmitter in elderly patients with chronic insomnia

    Directory of Open Access Journals (Sweden)

    Ji-Peng Zhu

    2016-12-01

    Full Text Available Objective: To analyze the effect of escitalopram combined with zolpidem on sleep structure, sleep process and neurotransmitter in elderly patients with chronic insomnia. Methods: A total of 112 elderly patients with chronic insomnia treated in our hospital were included in the study and randomly divided into observation group and control group (n=56. Control group received zolpidem therapy alone, observation group received escitalopram combined with zolpidem therapy, and then differences in sleep structure and process, neurotransmitter, stress hormones, hypothalamus-pituitary-thyroid axis indexes and so on were compared between two groups of patients. Results: The sleep structure and sleep process parameters SL, RL and S2 levels of observation group after treatment were significantly lower than those of control group while TST, S3 and REM levels were significantly higher than those of control group; Orexin, ACTH, 5-HT, NE, CRH, E, AngⅡ, Cor, ALD, DA and TGA content in serum were significantly lower than those of control group while T3, T4, TSH and TRH content were significantly higher than those of control group. Conclusions: Escitalopram combined with zolpidem can optimize the sleep structure and process in elderly patients with chronic insomnia, and also plays a prominent role in regulating the body's homeostasis.

  18. 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...

  19. Formulation and Evaluation of New Glimepiride Sublingual Tablets

    Directory of Open Access Journals (Sweden)

    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.

  20. Quantitative electroencephalography within sleep/wake states differentiates GABAA modulators eszopiclone and zolpidem from dual orexin receptor antagonists in rats.

    Science.gov (United States)

    Fox, Steven V; Gotter, Anthony L; Tye, Spencer J; Garson, Susan L; Savitz, Alan T; Uslaner, Jason M; Brunner, Joseph I; Tannenbaum, Pamela L; McDonald, Terrence P; Hodgson, Robert; Yao, Lihang; Bowlby, Mark R; Kuduk, Scott D; Coleman, Paul J; Hargreaves, Richard; Winrow, Christopher J; Renger, John J

    2013-11-01

    Dual orexin receptor antagonists (DORAs) induce sleep by blocking orexin 1 and orexin 2 receptor-mediated activities responsible for regulating wakefulness. DORAs represent a potential alternative mechanism to the current standard of care that includes the γ-aminobutyric acid (GABA)A receptor-positive allosteric modulators, eszopiclone and zolpidem. This work uses an innovative method to analyze electroencephalogram (EEG) spectral frequencies within sleep/wake states to differentiate the effects of GABAA modulators from DORA-22, an analog of the DORA MK-6096, in Sprague-Dawley rats. The effects of low, intermediate, and high doses of eszopiclone, zolpidem, and DORA-22 were examined after first defining each compound's ability to promote sleep during active-phase dosing. The EEG spectral frequency power within specific sleep stages was calculated in 1-Hz intervals from 1 to 100 Hz within each sleep/wake state for the first 4 h after the dose. Eszopiclone and zolpidem produced marked, dose-responsive disruptions in sleep stage-specific EEG spectral profiles compared with vehicle treatment. In marked contrast, DORA-22 exhibited marginal changes in the spectral profile, observed only during rapid eye movement sleep, and only at the highest dose tested. Moreover, while eszopiclone- and zolpidem-induced changes were evident in the inactive period, the EEG spectral responses to DORA-22 were absent during this phase. These results suggest that DORA-22 differs from eszopiclone and zolpidem whereby DORA-22 promotes somnolence without altering the neuronal network EEG activity observed during normal sleep.

  1. 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

  2. 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....

  3. Photocatalytic Reduction of Hexavalent Chromium Induced by Photolysis of Ferric/tartrate Complex

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Xianghua; Ding, Shimin; Zhang, Lixian [Yangtze Normal Univ., Fuling (China)

    2012-11-15

    Photocatalytic reduction of hexavalent chromium (Cr(VI)) in ferric-tartrate system under irradiation of visible light was investigated. Effects of light resources, initial pH value and initial concentration of various reactants on Cr(VI) photocatalytic reduction were studied. Photoreaction kinetics was discussed and a possible photochemical pathway was proposed. The results indicate that Fe(III)-tartrate system is able to rapidly and effectively photocatalytically reduce Cr(VI) utilizing visible light. Initial pH variations results in the concentration changes of Fe(III)-tartrate complex in this system, and pH at 3.0 is optimal for Cr(VI) photocatalytic reduction. Efficiency of Cr(VI) photocatalytic reduction increases with increasing initial concentrations of Cr(VI), Fe(III) and tartrate. Kinetics analysis indicates that initial Fe(III) concentration affects Cr(VI) photoreduction most significantly.

  4. Effects of sodium tartrate anodizing on fatigue life of TA15 titanium alloy

    Directory of Open Access Journals (Sweden)

    Fu Chunjuan

    2015-08-01

    Full Text Available Anodizing is always used as an effective surface modification method to improve the corrosion resistance and wear resistance of titanium alloy. The sodium tartrate anodizing is a new kind of environmental anodizing method. In this work, the effects of sodium tartrate anodizing on mechanical property were studied. The oxide film was performed on the TA15 titanium alloy using sodium tartrate as the film former. The effects of this anodizing and the traditional acid anodizing on the fatigue life of TA15 alloy were compared. The results show that the sodium tartrate anodizing just caused a slight increase of hydrogen content in the alloy, and had a slight effect on the fatigue life. While, the traditional acid anodizing caused a significant increase of hydrogen content in the substrate and reduced the fatigue life of the alloy significantly.

  5. Age-related changes in slow wave activity rise time and NREM sleep EEG with and without zolpidem in healthy young and older adults

    Science.gov (United States)

    Chinoy, Evan D.; Frey, Danielle J.; Kaslovsky, Daniel N.; Meyer, Francois G.; Wright, Kenneth P.

    2015-01-01

    Objective Whether there are age-related changes in slow wave activity (SWA) rise time, a marker of homeostatic sleep drive, is unknown. Additionally, although sleep medication use is highest among older adults, the quantitative electroencephalographic (EEG) profile of the most commonly prescribed sleep medication, zolpidem, in older adults is also unknown. We therefore quantified age-related and regional brain differences in sleep EEG with and without zolpidem. Methods Thirteen healthy young adults aged 21.9 ± 2.2 years and 12 healthy older adults aged 67.4 ± 4.2 years participated in a randomized, double-blind, within-subject study that compared placebo to 5 mg zolpidem. Results Older adults showed a smaller rise in SWA and zolpidem increased age-related differences in SWA rise time such that age differences were observed earlier after latency to persistent sleep. Age-related differences in EEG power differed by brain region. Older, but not young, adults showed zolpidem-dependent reductions in theta and alpha frequencies. Zolpidem decreased stage 1 in older adults and did not alter other age-related sleep architecture parameters. Conclusions SWA findings provide additional support for reduced homeostatic sleep drive or reduced ability to respond to sleep drive with age. Consequences of reduced power in theta and alpha frequencies in older adults remain to be elucidated. PMID:24980066

  6. Assessment of the abuse liability of a dual orexin receptor antagonist: a crossover study of almorexant and zolpidem in recreational drug users.

    Science.gov (United States)

    Cruz, Hans G; Hoever, Petra; Chakraborty, Bijan; Schoedel, Kerri; Sellers, Edward M; Dingemanse, Jasper

    2014-04-01

    Dual orexin receptor antagonists (DORAs) enable initiation and maintenance of sleep in patients with primary insomnia. Blockade of the orexin system has shown reduction of drug-seeking behavior in animal studies, supporting the role of orexin antagonism as a novel approach for treating substance abuse. Since hypnotics are traditionally associated with misuse, a lack of abuse liability of DORAs would offer significant benefits over current therapies for sleep disorders. In this randomized, crossover, proof-of-concept study, single oral doses of the DORA almorexant (200, 400, and 1,000 mg) were administered to healthy subjects with previous non-therapeutic experience with central nervous system depressants and were compared with placebo and single oral doses of zolpidem (20 and 40 mg), a benzodiazepine-like drug. Subjective measures of abuse potential (visual analog scales [VAS], Addiction Research Center Inventory, and Subjective Drug Value) and objective measures (divided attention [DA]) were evaluated over 24 h post-dose in 33 evaluable subjects. Drug Liking VAS peak effect (E max; primary endpoint) was significantly higher for all doses of almorexant and zolpidem compared with placebo (pDrug Liking' than both zolpidem doses (peffects than zolpidem 20 mg (peffects compared with zolpidem. Almorexant also showed less cognitive impairment compared with zolpidem on most DA endpoints. This study in humans investigating single doses of almorexant is the first to explore and show abuse liability of a DORA, a class of compounds that is not only promising for the treatment of sleep disorders, but also of addiction.

  7. [Tolerance to exertion after sleep reduction and after taking a hypnotic: zolpidem].

    Science.gov (United States)

    Mougin, F; Simon-Rigaud, M L; Davenne, D; Bourdin, H; Guilland, J C; Kantelip, J P; Magnin, P

    1992-01-01

    The aim of the present study was to investigate the effects of a delayed bedtime (3 a.m.), an advanced rising (3 a.m.), a sleep under placebo and under a hypnotic compound, i.e. 10 mg of zolpidem (Stilnox) on sleep structure and on the adaptations to a subsequent exercise in 8 male athletes. The chronology of these nights was randomized and each treatment administered in a double blind fashion. During each experimental night, subjects were monitored with conventional EEG/EOG/EMG polygraphic recordings. The next day, athletic performance was tested using a bicycle ergometer. A codified exercise was performed and consisted to a 10 min warm up followed by a 30 min steady state cycling corresponding to 75% of predetermined VO2 max. Then the work load increased progressively by steps of 10 W every minute until exhaustion. The recovery lasted 30 min. Heart rate, ventilation, VO2, ERO2 were monitored during all exercise and recovery. Plasma lactates and catecholamines were also measured at the same time. The data concerning sleep recordings showed that both nights with partial sleep deprivation resulted in a drop of time spent in slow wave sleep II (decrease of 55%) and in rapid eye movement sleep (decrease of 45%) while the amount of slow wave sleep III and IV were identical to that observed after the reference night. The sleep onset latency and the amount of sleep in stage I was reduced only after the delayed bedtime. Sleep data under zolpidem did not show any significantly difference in the amount of different sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Effect of brimonidine tartrate 0.2% ophthalmic solution on pupil size.

    Science.gov (United States)

    Kesler, Anat; Shemesh, Gabi; Rothkoff, Levi; Lazar, Moshe

    2004-08-01

    To evaluate the effect of brimonidine tartrate 0.2% ophthalmic solution on pupil size under scotopic and photopic luminance conditions in persons considering laser refractive surgery. Ophthalmic Health Center, Tel Aviv, Israel. The pupil size was measured in 36 eyes of 36 participants under scotopic and photopic conditions using the Colvard pupillometer (Oasis Medical) before and after brimonidine tartrate drops were administered. The pupil size was subsequently measured after 30 minutes and 4 and 6 hours. No difference was found in pupil size before brimonidine tartrate instillation in eyes with light or dark irides. Before instillation, the mean photopic pupil size was 4.81 mm +/- 0.54 (SD) (range 4.0 to 6.0 mm). At 30 minutes, all pupils became miotic, with a mean size of 3.77 +/- 0.51 mm (range 3.0 to 5.0 mm) (Pbrimonidine tartrate administration, the mean scotopic pupil size was 6.22 +/- 0.73 mm (range 5.0 to 8.0 mm). There was significant miosis to 4.57 +/- 0.84 mm (range 3.0 to 6.5 mm) (Pbrimonidine tartrate was stronger in eyes with light irides. Brimonidine tartrate caused significant miosis, especially under scotopic conditions, most likely from its alpha-2 adrenergic effect. Under photopic luminance conditions, the miotic effect was pronounced.

  9. 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...

  10. Severe Corneal Disorders Developed After Brimonidine Tartrate Ophthalmic Solution Use.

    Science.gov (United States)

    Maruyama, Yuko; Ikeda, Yoko; Yokoi, Norihiko; Mori, Kazuhiko; Kato, Hiroaki; Ueno, Morio; Kinoshita, Shigeru; Sotozono, Chie

    2017-12-01

    The primary side effects associated with 0.1% brimonidine tartrate (BT) ophthalmic solution with sodium chlorite are allergic conjunctivitis, blepharitis, and conjunctival hyperemia. However, cornea-related side effects are rare. In this study, we report 2 similar cases in which corneal neovascularization, corneal infiltration, and corneal opacity developed after BT eye-drop use. Retrospective report of 2 cases of corneal infiltration after BT eye-drop use. Case 1 involved a 78-year-old woman with follicular conjunctivitis, corneal neovascularization, and infiltration in her left eye after unilateral instillation of BT eye drops in that eye. Case 2 involved a 75-year-old woman with bilateral corneal neovascularization and infiltration after instillation of BT eye drops. In both cases, the corneal complications were deemed to be side effects of BT, so those eye drops were replaced with 0.1% fluorometholone eye drops. After replacement, blepharitis and corneal neovascularization successfully resolved; however, a layer of opacity remained across the transparent layer of the cornea in both cases. We encountered 2 cases of corneal and conjunctival complications that developed as side effects after BT eye-drop use, thus indicating that strict attention should be paid to the possibility of side effects after initiation of antiglaucoma eye-drop use.

  11. Statistically optimised ethosomes for transdermal delivery of tolterodine tartrate.

    Science.gov (United States)

    Prasanthi, D; Lakshmi, P K

    2013-11-01

    The aim of the current investigation is to optimize ethosomes statistically for enhancing transdermal potential of Tolterodine Tartrate (TT). Ethosomes bearing TT were prepared by cold method and characterized for various parameters like vesicle size, vesicle shape, surface morphology and % drug entrapment. Microscopic examinations suggest ethosomes as spherical unilamellar vesicles with a smooth surface. Optimized ethosomal vesicles were of 890±2.67nm size and showed 79.83±3.18% drug entrapment. Ex-vivo permeation studies across rat skin resulted in increased flux of 4.69±0.24μg/cm(2)/hr and decreased lag time of 0.13±0.05 hr when compared with drug solution (0.546±0.05μg/cm(2)/hr, 3±0.2 hr).This shows enhancement of transdermal delivery by 8.82 times. Anatomical changes in skin samples due to vesicle-skin interaction were observed on histological examination. Optimized formulation on storage at 4°C for 120 days showed insignificant growth in vesicular size revealing low aggregation of vesicles. The results collectively suggest ethosomes as carriers for accentuated transdermal delivery of TT.

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

    Science.gov (United States)

    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.

  13. Synthesis and in vivo evaluation of [{sup 11}C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dumont, Filip; Waterhouse, Rikki N. E-mail: rnw7@columbia.edu; Montoya, Julie A.; Mattner, Filomena; Katsifis, Andrew; Kegeles, Lawrence S.; Laruelle, Marc

    2003-05-01

    The synthesis and evaluation of [{sup 11}C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [{sup 11}C] methyl iodide afforded the title compound [{sup 11}C]zolpidem in a yield of 19.19 {+-} 3.23% in 41 {+-} 2 min in specific activities of 0.995-1.19 Ci/{mu}mol (1.115 {+-} 0.105 Ci/{mu}mol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 {+-} 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [{sup 11}C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors.

  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. Two-chiral component microemulsion EKC - chiral surfactant and chiral oil. Part 2: diethyl tartrate.

    Science.gov (United States)

    Kahle, Kimberly A; Foley, Joe P

    2007-08-01

    In this second study on dual-chirality microemulsions containing a chiral surfactant and a chiral oil, a less hydrophobic and lower interfacial tension chiral oil, diethyl tartrate, is employed (Part 1, Foley, J. P. et al.., Electrophoresis, DOI: 10.1002/elps.200600551). Six stereochemical combinations of dodecoxycarbonylvaline (DDCV: R, S, or racemic, 2.00% w/v), racemic 2-hexanol (1.65% v/v), and diethyl tartrate (D, L, or racemic, 0.88% v/v) were examined as pseudostationary phases (PSPs) for the enantioseparation of six chiral pharmaceutical compounds: pseudoephedrine, ephedrine, N-methyl ephedrine, metoprolol, synephrine, and atenolol. Average efficiencies increased with the addition of a chiral oil to R-DDCV PSP formulations. Modest improvements in resolution and enantioselectivity (alpha(enant)) were achieved with two-chiral-component systems over the one-chiral-component microemulsion. Slight enantioselective synergies were confirmed using a thermodynamic model. Results obtained in this study are compared to those obtained in Part 1 as well as those obtained with chiral MEEKC using an achiral, low-interfacial-tension oil (ethyl acetate). Dual-chirality microemulsions with the more hydrophobic oil dibutyl tartrate yielded, relative to diethyl tartrate, higher efficiencies (100,000-134,000 vs. 80,800-94,300), but lower resolution (1.64-1.91 vs. 2.08-2.21) due to lower enantioselectivities (1.060-1.067 vs. 1.078-1.081). Atenolol enantiomers could not be separated with the dibutyl tartrate-based microemulsions but were partially resolved using diethyl tartrate microemulsions. A comparable single-chirality microemulsion based on the achiral oil ethyl acetate yielded, relative to diethyl tartrate, lower efficiency (78 300 vs. 91 600), higher resolution (1.99 vs. 1.83), and similar enantioselectivities.

  16. Long-Term Maintenance of Therapeutic Gains Associated With Cognitive-Behavioral Therapy for Insomnia Delivered Alone or Combined With Zolpidem.

    Science.gov (United States)

    Beaulieu-Bonneau, Simon; Ivers, Hans; Guay, Bernard; Morin, Charles M

    2017-03-01

    To document the long-term sleep outcomes at 12 and 24 months after patients with chronic insomnia were treated with cognitive-behavioral therapy (CBT), either singly or combined with zolpidem medication. Participants were 160 adults with chronic insomnia. They were first randomized for a six-week acute treatment phase involving CBT alone or CBT combined with nightly zolpidem, and randomized for a six-month extended treatment phase involving CBT, no additional treatment, CBT combined with zolpidem as needed, or CBT with zolpidem tapered. This paper reports results of the 12- and 24-month follow-ups on the main outcome measures derived from the Insomnia Severity Index and sleep diaries. Clinical improvements achieved 6 months following the end of treatment were well-maintained in all four conditions, with insomnia remission rates ranging from 48% to 74% at the 12-month follow-up, and from 44% to 63% at the 24-month follow-up. Participants receiving CBT with zolpidem taper in the extended treatment phase had significantly better results than those receiving CBT with continued zolpidem as needed. The magnitude of improvements on sleep diary parameters was similar between conditions, with a slight advantage for the CBT with zolpidem taper condition. The addition of extended CBT did not alter the long-term outcome over improvements obtained during the initial 6-week CBT. The results suggest that CBT for insomnia, when delivered alone or in combination with medication, produce durable sleep improvements up to two years after completion of treatment. These long-term results indicate that even if a combined CBT plus medication approach provide an added benefit immediately after treatment, extending CBT while tapering medication produce better sustained improvements compared to continued use of medication as needed.

  17. The role of brimonidine tartrate gel in the treatment of rosacea

    Directory of Open Access Journals (Sweden)

    Jackson JM

    2015-10-01

    Full Text Available J Mark Jackson,1 Melissa Knuckles,2 John Paul Minni,3 Sandra Marchese Johnson,4, Kevin Tate Belasco5 1Division of Dermatology, University of Louisville, Louisville, KY, USA; 2PSC, Dermatology, Corbin, KY, USA; 3Waters Edge Dermatology, Stuart, FL, USA; 4Johnson Dermatology, Fort Smith, AR, USA; 5Blue Harbor Dermatology, Newport Beach, CA, USA Abstract: Rosacea is a chronic cutaneous condition with a prevalence rate ranging from 9.6% to 22% in recent studies. Facial erythema (transient and permanent is considered a common denominator that is frequently observed in all subtypes of rosacea and is estimated to affect more than 40 million people worldwide. Brimonidine tartrate is a selective α2-adrenergic receptor agonist and is the first topical treatment approved for facial erythema of rosacea. Clinical trials have demonstrated that brimonidine tartrate provided significantly greater efficacy, compared to vehicle, for the treatment of moderate to severe erythema of rosacea. In addition, brimonidine tartrate has demonstrated a rapid onset of effect, duration of action throughout the day, and good safety profile in studies of up to 1 year. This review critically discusses the role of brimonidine tartrate for the treatment of facial erythema of rosacea by examining both clinical study data and real-world dermatologist experiences across a wide spectrum of treated patients, and concludes that it is a significant therapeutic option in the management of an unmet need of this chronic condition. Keywords: rosacea, brimonidine tartrate, erythema, adverse event

  18. Elevated serum tartrate-resistant acid phosphatase isoform 5a levels in metabolic syndrome.

    Science.gov (United States)

    Huang, Yi-Jhih; Huang, Tsai-Wang; Chao, Tsu-Yi; Sun, Yu-Shan; Chen, Shyi-Jou; Chu, Der-Ming; Chen, Wei-Liang; Wu, Li-Wei

    2017-09-29

    Tartrate-resistant phosphatase isoform 5a is expressed in tumor-associated macrophages and is a biomarker of chronic inflammation. Herein, we correlated serum tartrate-resistant phosphatase isoform 5a levels with metabolic syndrome status and made comparisons with traditional markers of inflammation, including c-reactive protein and interleukin-6. One hundred healthy volunteers were randomly selected, and cut-off points for metabolic syndrome related inflammatory biomarkers were determined using receiver operating characteristic curves. Linear and logistic regression models were subsequently used to correlate inflammatory markers with the risk of metabolic syndrome. Twenty-two participants met the criteria for metabolic syndrome, and serum tartrate-resistant phosphatase isoform 5a levels of >5.8 μg/L were associated with metabolic syndrome (c-statistics, 0.730; p = 0.001; 95% confidence interval, 0.618-0.842). In addition, 1 μg/L increases in tartrate-resistant phosphatase isoform 5a levels were indicative of a 1.860 fold increase in the risk of metabolic syndrome (p = 0.012). Elevated serum tartrate-resistant phosphatase isoform 5a levels are associated with the risk of metabolic syndrome, with a cut-off level of 5.8 μg/L.

  19. Development and Evaluation of Novel Polymeric Nanoparticles of Brimonidine Tartrate.

    Science.gov (United States)

    Singh, Kavita H; Shinde, Ujwala A

    2010-07-01

    Micro and nanoparticulate carriers have been in focus in ophthalmic drug delivery with the objective of improving bioavailability, drug targeting and reducing pulse entry of the drug in ocular cul de sac. Polymeric nanoparticles for ocular purpose have potential in reducing the pulse entry and frequency of dosing, thus improving patient compliance. In the present study, mucoadhesive sodium alginate nanoparticles were developed for Brimonidine Tartrate (BT) as a model antiglaucoma drug by controlled ionic gelation technique. These nanoparticles would not only prolong drugs residence time but also reduce pulse entry in cul de sac. Nanoparticles were evaluated for morphology, surface characteristics, drug polymer interactions, particle size, polydispersibility index, zeta potential, entrapment efficiency, in vitro release profile and in vivo efficacy. The effect of various stabilizers on stabilization of blank and drug loaded nanoparticles was investigated. Irregular shape and loss of crystallinity for BT loaded sodium alginate nanoparticles was observed by TEM and SEM images respectively. IR spectra and DSC thermograms revealed the physicochemical interaction was involved during sodium alginate nanoparticle formation and entrapment of BT. The developed nanoparticles have average particle size of 450nm with PI 0.65, the entrapment efficiency ranged from 4-18 % and zeta potential values ranged from -27.5 mV to -24.1 mV. In vitro release profile showed a gradual drug release over the period of 3 hrs. In-vivo experiments showed that it was possible to prolong the drug release over a period of 8 hr, on topical instillation of BT loaded nanoparticles to albino rabbits, hence reducing the dosage frequency.

  20. Is Zolpidem Associated with Increased Risk of Fractures in the Elderly with Sleep Disorders? A Nationwide Case Cross-Over Study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Yih-Jing Tang

    Full Text Available We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly.Case-crossover design.Elderly enrollees (n = 6010 in Taiwan's National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures.After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant.Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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....

  8. 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...

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Effects of zolpidem on sedation, anxiety, and memory in the plus-maze discriminative avoidance task.

    Science.gov (United States)

    Zanin, Karina A; Patti, Camilla L; Sanday, Leandro; Fernandes-Santos, Luciano; Oliveira, Larissa C; Poyares, Dalva; Tufik, Sergio; Frussa-Filho, Roberto

    2013-04-01

    Zolpidem (Zolp), a hypnotic drug prescribed to treat insomnia, may have negative effects on memory, but reports are inconsistent. We examined the effects of acute doses of Zolp (2, 5, or 10 mg/kg, i.p.) on memory formation (learning, consolidation, and retrieval) using the plus-maze discriminative avoidance task. Mice were acutely treated with Zolp 30 min before training or testing. In addition, the effects of Zolp and midazolam (Mid; a classic benzodiazepine) on consolidation at different time points were examined. The possible role of state dependency was investigated using combined pre-training and pre-test treatments. Zolp produced a dose-dependent sedative effect, without modifying anxiety-like behavior. The pre-training administration of 5 or 10 mg/kg resulted in retention deficits. When administered immediately after training or before testing, memory was preserved. Zolp post-training administration (2 or 3 h) impaired subsequent memory. There was no participation of state dependency phenomenon in the amnestic effects of Zolp. Similar to Zolp, Mid impaired memory consolidation when administered 1 h after training. Amnestic effects occurred when Zolp was administered either before or 2-3 h after training. These memory deficits are not related to state dependency. Moreover, Zolp did not impair memory retrieval. Notably, the memory-impairing effects of Zolp are similar to those of Mid, with the exception of the time point at which the drug can modify consolidation. Finally, the memory effects were unrelated to sedation or anxiolysis.

  18. 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.

  19. 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.

  20. 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.

  1. Rapid determination of benzodiazepines, zolpidem and their metabolites in urine using direct injection liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Jeong, Yu-Dong; Kim, Min Kyung; Suh, Sung Ill; In, Moon Kyo; Kim, Jin Young; Paeng, Ki-Jung

    2015-12-01

    Benzodiazepines and zolpidem are generally prescribed as sedative, hypnotics, anxiolytics or anticonvulsants. These drugs, however, are frequently misused in drug-facilitated crime. Therefore, a rapid and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for identification and quantification of benzodiazepines, zolpidem and their metabolites in urine using deuterium labeled internal standards (IS). Urine samples (120 μL) mixed with 80 μL of the IS solution were centrifuged. An aliquot (5 μL) of the sample solution was directly injected into the LC-MS/MS system for analysis. The mobile phases consisted of water and acetonitrile containing 2mM ammonium trifluoroacetate and 0.2% acetic acid. The analytical column was a Zorbax SB-C18 (100 mm × 2.1 mm i.d., 3.5 μm, Agilent). The separation and detection of 18 analytes were achieved within 10 min. Calibration curves were linear over the concentration ranges of 0.5-20 ng/mL (zolpidem), 1.0-40 ng/mL (flurazepam and temazepam), 2.5-100 ng/mL (7-aminoclonazepam, 1-hydroxymidazolam, midazolam, flunitrazepam and alprazolam), 5.0-200 ng/mL (zolpidem phenyl-4-carboxylic acid, α-hydroxyalprazolam, oxazepam, nordiazepam, triazolam, diazepam and α-hydroxytriazolam), 10-400 ng/mL (lorazepam and desalkylflurazepam) and 10-100 ng/mL (N-desmethylflunitrazepam) with the coefficients of determination (r(2)) above 0.9971. The dilution integrity of the analytes was examined for supplementation of short linear range. Dilution precision and accuracy were tested using two, four and ten-folds dilutions and they ranged from 3.7 to 14.4% and -12.8 to 12.5%, respectively. The process efficiency for this method was 63.0-104.6%. Intra- and inter-day precisions were less than 11.8% and 9.1%, while intra- and inter-day accuracies were less than -10.0 to 8.2%, respectively. The lower limits of quantification were lower than 10 ng/mL for each analyte. The applicability of the developed method was successfully

  2. Pupillometry study of brimonidine tartrate 0.2% and apraclonidine 0.5%.

    Science.gov (United States)

    Besada, Eulogio; Reed, Kimberly; Najman, Perla; Shechtman, Diana; Hardigan, Patrick

    2011-12-01

    This study investigated possible effects of brimonidine tartrate 0.2% and apraclonidine 0.5% on pupil diameter. Ten subjects between 20 and 40 years of age participated. A Colvard pupillometer (Oasis Medical) was used to measure pupil diameter. Baseline and serial measurements were obtained at 3 luminance levels (>6.4, brimonidine tartrate 0.2% or apraclonidine 0.5% in one eye versus a placebo in the contralateral eye. The measurements for each drug were obtained on different days. A nested random effects model controlling for subject's age, race, and sex was used for statistical analysis. A maximum reduction in pupil diameter was observed at 90 minutes from instillation (1.40 mm at >6.4 cd/m(2), 1.69 mm at brimonidine tartrate 0.2%. At all time intervals and illumination levels, miosis (P Brimonidine tartrate 0.2% produced a moderate miotic effect. No effect was observed for apraclonidine 0.5%. A predominant agonistic effect on α-2 receptors of the iris dilator may explain this behavior.

  3. The role of brimonidine tartrate gel in the treatment of rosacea.

    Science.gov (United States)

    Jackson, J Mark; Knuckles, Melissa; Minni, John Paul; Johnson, Sandra Marchese; Belasco, Kevin Tate

    2015-01-01

    Rosacea is a chronic cutaneous condition with a prevalence rate ranging from 9.6% to 22% in recent studies. Facial erythema (transient and permanent) is considered a common denominator that is frequently observed in all subtypes of rosacea and is estimated to affect more than 40 million people worldwide. Brimonidine tartrate is a selective α2-adrenergic receptor agonist and is the first topical treatment approved for facial erythema of rosacea. Clinical trials have demonstrated that brimonidine tartrate provided significantly greater efficacy, compared to vehicle, for the treatment of moderate to severe erythema of rosacea. In addition, brimonidine tartrate has demonstrated a rapid onset of effect, duration of action throughout the day, and good safety profile in studies of up to 1 year. This review critically discusses the role of brimonidine tartrate for the treatment of facial erythema of rosacea by examining both clinical study data and real-world dermatologist experiences across a wide spectrum of treated patients, and concludes that it is a significant therapeutic option in the management of an unmet need of this chronic condition.

  4. The role of brimonidine tartrate gel in the treatment of rosacea

    Science.gov (United States)

    Jackson, J Mark; Knuckles, Melissa; Minni, John Paul; Johnson, Sandra Marchese; Belasco, Kevin Tate

    2015-01-01

    Rosacea is a chronic cutaneous condition with a prevalence rate ranging from 9.6% to 22% in recent studies. Facial erythema (transient and permanent) is considered a common denominator that is frequently observed in all subtypes of rosacea and is estimated to affect more than 40 million people worldwide. Brimonidine tartrate is a selective α2-adrenergic receptor agonist and is the first topical treatment approved for facial erythema of rosacea. Clinical trials have demonstrated that brimonidine tartrate provided significantly greater efficacy, compared to vehicle, for the treatment of moderate to severe erythema of rosacea. In addition, brimonidine tartrate has demonstrated a rapid onset of effect, duration of action throughout the day, and good safety profile in studies of up to 1 year. This review critically discusses the role of brimonidine tartrate for the treatment of facial erythema of rosacea by examining both clinical study data and real-world dermatologist experiences across a wide spectrum of treated patients, and concludes that it is a significant therapeutic option in the management of an unmet need of this chronic condition. PMID:26566370

  5. DISSOLUTION KINETICS OF KETANSERIN TARTRATE, THE SALT OF A WEAKLY BASIC DRUG

    NARCIS (Netherlands)

    VANDERVEEN, J; BUITENDIJK, HH; LERK, CF

    1992-01-01

    The rotating disc method was used to study the dissolution kinetics of ketanserin tartrate, the salt of a weakly basic drug. Both solubility and dissolution rate decrease exponentially with increasing pH of the dissolution medium. A plot of the logarithm of the ratio of dissolution rate to

  6. [Biological profile of tartrate-resistant acid phosphatase as a marker of bone resorption].

    Science.gov (United States)

    Rico, H; Iritia, M; Arribas, I; Revilla, M

    1990-12-01

    Tartrate-resistant serum acid phosphatase was measured in 123 subjects, 80 of which were normal and the rest pathologic, in order to define the profile and value of this parameter as a biological marker of osteoclastic activity. Normal subjects were divided into age groups based on the period where skeletal growth ends (under 20 years), at the age of menopause in women (50 years, between 20 and 50 years) and those over 50 years. There was an increase in tartrate-resistant serum acid phosphatase coinciding with puberty and no sex differences were observed after the 50 year mark, when women showed higher values than men (p less than 0.001). Such tartrate-resistant serum acid phosphatase increase, is reflected as higher values in the 50 year group than in the 20 to 50 year group (p less than 0.001), the only age limit where a negative significant correlation between tartrate-resistant serum acid phosphatase values and age could be observed (p less than 0.05). Values were higher up to the age of 20 years (p less than 0.001) than in any other older age group. Levels increased significantly (p less than 0.001 for both groups) in post-menopausal osteoporosis (n = 20) and in Paget's disease of bone (n = 15), and decreased significantly (p less than 0.05) in imperfect osteogenesis (n = 8), thus revealing its value as a biological marker of osteoclastic activity.

  7. Subchronic toxicity experiment with rats fed a diet containing ergotamine-tartrate

    NARCIS (Netherlands)

    Speijers GJA; Wester PW; van Leeuwen FXR; de la Fonteyne-Blankestijn LJJ; Post W; van Egmond HP; Sizoo EA; Janssen GB

    1993-01-01

    In a subchronic toxicity study 4 groups of 10 Sprague-Dawley rats/group/sex received 0, 5, 20 and 80 mg ergotamine tartrate (EAT)/kg diet respectively during 13 weeks. Food intake and water intake were measured twice a week. Body weight gain was recorded weekly. After 7 weeks and 12 weeks urine

  8. Incorporation of Zolpidem into Hair and Its Distribution after a Single Administration.

    Science.gov (United States)

    Shima, Noriaki; Sasaki, Keiko; Kamata, Tooru; Matsuta, Shuntaro; Wada, Misato; Kakehashi, Hidenao; Nakano, Shihoko; Kamata, Hiroe; Nishioka, Hiroshi; Sato, Takako; Tsuchihashi, Hitoshi; Miki, Akihiro; Katagi, Munehiro

    2017-03-01

    To obtain fundamental information on the drug incorporation into hair, time-course changes in drug distribution along single-strand hair were observed after a single oral administration of zolpidem (ZP), one of the most frequently used hypnotic agents. Quantitative sectional hair analyses of 1-mm segments were performed for each single-strand hair using a validated LC-MS/MS procedure. ZP was detected in all specimens plucked at 10 and 24 hours after a single dose, and the distribution ranged over the whole hair root (4-5 mm in length). A significantly high concentration of ZP was detected in the hair bulb region, whereas much lower concentrations were widely observed in the upper part of the hair root of those samples; this suggested that the incorporation of ZP occurred in two regions, mainly in the hair bulb and to a lesser extent in the upper dermis zone. The ZP-positive area formed lengths of up to 10-12 mm after a single administration, indicating that its incorporation from the hair bulb would continue for about 2 weeks. Time-course changes in the ZP concentration in the hair root additionally revealed that only a small portion of ZP that initially concentrated in the bulb was successively incorporated into the hair matrix and moved toward the keratinized region as hair grew. These findings should be taken into account upon discussing individual drug-use history based on hair analysis. The matrix-assisted laser desorption/ionization mass spectrometry imaging of ZP in the same kinds of hair specimens was also successfully achieved. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Formulation and evaluation of new long acting metoprolol tartrate ophthalmic gels

    Science.gov (United States)

    Abou el Ela, Amal El Sayeh F.; Khatib, Mona Mohamed El

    2014-01-01

    The rationale of the present work is to formulate and evaluate metoprolol tartrate (MT), which is a beta-1 selective adrenergic blocking agent in a new ocular gel delivery system; this is our way and method to increase its contact to the cornea, giving a longer time of drug contact to the eye and slow possible release from the preparation. Metoprolol tartrate is chosen as a candidate for gel formulation because although it has been available for a few years as ophthalmic solutions, it has not been marketed as an ocular gel yet. Two polymers; Carbopol 934 and Pluronic F127 (PF127) were used in two different concentrations in this study. Metoprolol tartrate was used in two concentrations, 0.5% and 1% (w/w). All formulations were exposed to visual examinations, pH measurement, in vitro release, rheological study and differential scanning calorimetry (DSC). Results showed that all formulations were clear, showed pH within the acceptable range suitable to be administered in the eye, and exhibited pseudoplastic flow behavior. DSC results concluded that, MT was compatible with different polymers used. In vitro release results showed that the release rate of metoprolol tartrate from gel preparations decreased as an inverse function of polymer concentration, and the release rate of the drug increased as the initial concentration increased. Intra-ocular pressure (IOP) measurements of rabbit’s eye treated with 1% (w/w) metoprolol tartrate in gel formulations with different concentrations of the polymer were determined. Carbopol 934 gel formulations showed that this polymer extended the duration of pressure reducing effect of MT to more than 5hr when compared with Pluronic F127 gel formulations. The area above the curve (AAC), maximum response, time of maximum response (tmax), and the duration of the drug action were also calculated. PMID:25561869

  10. Comparative in vitro assessment of tolterodine tartrate tablets by high performance liquid chromatographic (HPLC

    Directory of Open Access Journals (Sweden)

    Hossein Danafar

    2016-06-01

    Full Text Available Tolterodine tartrate, is a new, potent and competitive muscarinic receptor antagonist in clinical development for the treatment of urge incontinence and other symptoms of unstable bladder. The purpose of this study is to establish a reliable and quick method for the assignment of tolterodine tartrate by high performance liquid chromatography with ultraviolet detection (HPLC-UV. A rapid  and  sensitive  high  performance  liquid  chromatographic  (HPLC  method  has  been developed  for  determination  of  tolterodine tartrate.  Mobile phase was composed of phosphate acetate 0.1 M (pH 2.5-acetonitrile (50:50 v/v with a flow rate of 1.2 ml/min. The eluted peaks were detected by a UV detector was set at wavelength of 285 nm. The method was validated in the range of tolterodine tartrate concentrations from 10 to 100 µg/ml. The limits of detection (LOD and quantitation (LOQ of the method were 5 and 10 µg/ml, respectively. The average drug recovery was 98.20 % throughout the linear concentration range. The average within-run and between-run accuracy values of 98.56 % and 99.11 % respectively. Statistical  assessment  of  various  in  vitro  dissolution  parameters  and  assay  results was  also  conducted  to  establish  if  there were  any significant difference among them. The validated HPLC method has been used successfully to study tolterodine tartrate.

  11. 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.

  12. 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.

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

    Science.gov (United States)

    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.

  14. 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.

  15. Simultaneous ESI-APCI+ ionization and fragmentation pathways for nine benzodiazepines and zolpidem using single quadrupole LC-MS.

    Science.gov (United States)

    Galaon, Toma; Vacaresteanu, Catalina; Anghel, Dan-Florin; David, Victor

    2014-05-01

    Nine important 1,4-benzodiazepines and zolpidem were characterized by liquid chromatography-mass spectrometry using a multimode ionization source able to generate ions using both electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), and a single quadrupole mass analyzer. An optimum chromatographic separation was applied for all target compounds in less than 8 minutes using a Zorbax Eclipse Plus column (100 × 4.6 mm, 3.5 µm) kept at 35°C and a 0.3% HCOOH/ACN/IPA (61:34:5) mobile phase pumped at 1 ml/min. Optimization of LC-MS method generated low limit of quantitation (LOQ) values situated in the range 0.3-20.5 ng/ml. Comparison between differences in method sensitivity, under specified chromatographic conditions, when using ESI-only, APCI-only, and simultaneous ESI-APCI ionization with such a multimode source was discussed. Mixed ESI-APCI(+) mode proved to be the most sensitive ionization generating an average 35% detector response increase compared to ESI-only ionization and 350% detector response increase with respect to APCI-only ionization. Characterization of the nine benzodiazepines and zolpidem concerning their MS fragmentation pathway following 'in-source' collision-induced dissociation is discussed in detail and some general trends regarding these fragmentations are set. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Effects of GF-015535-00, a novel α1 GABA A receptor ligand, on the sleep-wake cycle in mice, with reference to zolpidem.

    Science.gov (United States)

    Anaclet, Christelle; Zhang, Mei; Zhao, Chunmei; Buda, Colette; Seugnet, Laurent; Lin, Jian-Sheng

    2012-01-01

    Novel, safe, and efficient hypnotic compounds capable of enhancing physiological sleep are still in great demand in the therapy of insomnia. This study compares the sleep-wake effects of a new α1 GABA(A) receptor subunit ligand, GF-015535-00, with those of zolpidem, the widely utilized hypnotic compound. Nine C57Bl6/J male mice were chronically implanted with electrodes for EEG and sleep-wake monitoring. Each mouse received 3 doses of GF-015535-00 and zolpidem. Time spent in sleep-wake states and cortical EEG power spectra were analyzed. Both zolpidem and GF-015535-00 prominently enhanced slow wave sleep and paradoxical sleep in the mouse. However, as compared with zolpidem, GF-015535-00 showed several important differences: (1) a comparable sleep-enhancing effect was obtained with a 10 fold smaller dose; (2) the induced sleep was less fragmented; (3) the risk of subsequent wake rebound was less prominent; and (4) the cortical EEG power ratio between slow wave sleep and wake was similar to that of natural sleep and thus compatible with physiological sleep. The characteristics of the sleep-wake effects of GF-015535-00 in mice could be potentially beneficial for its use as a therapeutic compound in the treatment of insomnia. Further investigations are required to assess whether the same characteristics are conserved in other animal models and humans.

  17. 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.

  18. 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.

  19. The discrimination of d-tartrate positive and d-tartrate negative S. enterica subsp. enterica serovar Paratyphi B isolated in Malaysia by phenotypic and genotypic methods.

    Science.gov (United States)

    Ahmad, Norazah; Hoon, Shirley Tang Gee; Ghani, Mohamed Kamel Abd; Tee, Koh Yin

    2012-06-01

    Serotyping is not sufficient to differentiate between Salmonella species that cause paratyphoid fever from the strains that cause milder gastroenteritis as these organisms share the same serotype Salmonella Paratyphi B (S. Paratyphi B). Strains causing paratyphoid fever do not ferment d-tartrate and this key feature was used in this study to determine the prevalence of these strains among the collection of S. Paratyphi B strains isolated from patients in Malaysia. A total of 105 isolates of S. Paratyphi B were discriminated into d-tartrate positive (dT+) and d-tartrate negative (dT) variants by two lead acetate test protocols and multiplex PCR. The lead acetate test protocol 1 differed from protocol 2 by a lower inoculum size and different incubation conditions while the multiplex PCR utilized 2 sets of primers targeting the ATG start codon of the gene STM3356. Lead acetate protocol 1 discriminated 97.1% of the isolates as S. Paratyphi B dT+ and 2.9% as dT while test protocol 2 discriminated all the isolates as S. Paratyphi B dT+. The multiplex PCR test identified all 105 isolates as S. Paratyphi B dT+ strains. The concordance of the lead acetate test relative to that of multiplex PCR was 97.7% and 100% for protocol 1 and 2 respectively. This study showed that S. Paratyphi B dT+ is a common causative agent of gastroenteritis in Malaysia while paratyphoid fever appears to be relatively uncommon. Multiplex PCR was shown to be a simpler, more rapid and reliable method to discriminate S. Paratyphi B than the phenotypic lead acetate test.

  20. 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.

  1. The antiparasitic drug, potassium antimony tartrate, inhibits tumor angiogenesis and tumor growth in nonsmall-cell lung cancer

    National Research Council Canada - National Science Library

    Wang, Beibei; Yu, Weiwei; Guo, Jiawei; Jiang, Xingwu; Lu, Weiqiang; Liu, Mingyao; Pang, Xiufeng

    .... In this article, we identified potassium antimonyl tartrate (PAT), an antiparasitic drug, as a novel agent to block angiogenesis by screening US Food and Drug Administration-approved chemical drugs...

  2. Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia

    National Research Council Canada - National Science Library

    Bettica, Paolo; Squassante, Lisa; Groeger, John A; Gennery, Brian; Winsky-Sommerer, Raphaelle; Dijk, Derk-Jan

    2012-01-01

    ...) and a positive control zolpidem (10 mg), an allosteric modulator of GABA(A) receptors. Objective and subjective sleep parameters and next-day performance were assessed in 51 healthy male volunteers in a traffic noise model of situational insomnia...

  3. Sorption of tartrate ions to lanthanum (III)-modified calcium fluor- and hydroxyapatite.

    Science.gov (United States)

    Aissa, Abdallah; Debbabi, Mongi; Gruselle, Michel; Thouvenot, René; Flambard, Alexandrine; Gredin, Patrick; Beaunier, Patricia; Tõnsuaadu, Kaia

    2009-02-01

    The present article details the formation of lanthanum-modified apatites and the binding process of tartrate ions with these obtained apatites. Chemical analyses, FT-IR and (31)P NMR spectroscopies, XRD powder, TGA, and TEM analyses were employed for studying the reaction between Ca(10)(PO(4))(6)(OH)(2) (HAp) or Ca(10)(PO(4))(6)(F)(2) (FAp) and LaCl(3). The reaction was found to take place mainly through partial dissolution of the apatite followed by precipitation of a new phase containing lanthanum phosphate. When La(3+) was introduced in the presence of L(+)-tartaric acid (TAH(2)), no fundamental changes were observed in the HAp or FAp structures. However, there did occur a formation of a new phase of Ca or/and La tartrate salt.

  4. 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.

  5. Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

    Science.gov (United States)

    Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

    2018-01-05

    The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the

  6. Effects of after-midnight intake of zolpidem and temazepam on driving ability in women with non-organic insomnia.

    Science.gov (United States)

    Partinen, M; Hirvonen, K; Hublin, C; Halavaara, M; Hiltunen, H

    2003-11-01

    Occasionally, insomniac patients may take a sleeping pill after midnight. This may have consequences on their ability to drive a car and result in an increased risk of car accidents. This double-blind, randomized, placebo-controlled, three-treatment three-period cross-over study investigated the effects of two frequently prescribed hypnotics of different classes in a real life condition on driving performance and psychomotor skills in insomniac women. Single doses of zolpidem 10 mg (Z), temazepam 20 mg (T) or placebo (P) were administered at 2:00 a.m. to 19 women aged 35-60 years in three treatment periods separated by wash-out periods of 3-14 days. After polysomnography at baseline and each treatment night, patients underwent, 5.5 h after drug intake at 7:30 a.m. on the next morning, a STISIM driving simulator test, and a subsequent neuropsychological test (FePsy). Eighteen insomniac women were included in the analysis (mean age 50 years, mean weight 69 kg, mean BMI 25.6 kg/m2). There were no differences between treatments for the primary outcome measure (mean time to collision; baseline: 0.120 s, P: 0.124, T: 0.118, Z: 0.124; P> or =0.12 for all pairwise comparisons). No differences were recorded for speed deviation and reaction time to tasks for the verum treatments, however, lane position deviation was greater after administration of zolpidem in comparison to both placebo and temazepam (P=0.025 and 0.05, respectively). There were no differences between treatments in the FePsy test. Both medications were well tolerated. 5.5 h after drug administration there were no major differences in psychomotor performances between both zolpidem and temazepam compared to placebo, which indicates the absence of significant residual effects at that time. However, certain patients were more susceptible than others to the drug effects (two patients with high number of collisions). This underlines the necessity to strongly advocate against the late intake of hypnotics if patients

  7. Aceclidine, brimonidine tartrate, and dapiprazole: comparison of miotic effect and tolerability under different lighting conditions.

    Science.gov (United States)

    Canovetti, Annalisa; Nardi, Marco; Figus, Michele; Fogagnolo, Paolo; Benelli, Umberto

    2009-01-01

    To evaluate the effect of 3 types of topically applied miotic eyedrops on the pupil diameter in normal eyes. Department of Neurosciences, Section of Ophthalmology, University of Pisa, Pisa, Italy. This prospective study comprised 60 eyes of 30 healthy volunteers treated with aceclidine 0.02%, brimonidine tartrate 0.20%, and dapiprazole 0.25%. Pupil diameter was measured under scotopic, mesopic (4 lux), and photopic (50 lux) conditions using an infrared pupillometer incorporated into a CSO topographer. The first measurement was obtained before single instillation of 1 type of miotic eyedrop. Subsequent measurements were taken after 30, 120, and 240 minutes. Each additional medication was tested after an interval of at least 6 weeks to avoid possible effects from the previously administered drug. All patients received a questionnaire and were asked to grade the tolerability of each eyedrop using a subjective scoring system. Aceclidine 0.02% had no significant miotic effect. Brimonidine tartrate 0.20% caused significant miosis within 30 minutes and 120 minutes; after 240 minutes, the effect under all luminance conditions decreased to baseline levels without reaching the initial level. Dapiprazole 0.25% had a miotic effect similar to that of brimonidine but produced many side effects including hyperemia and burning, which many patients said caused significant discomfort. Brimonidine tartrate 0.20% had the best miotic effect of the 3 agents tested and was well tolerated by the patients. The reproducible miotic effect of brimonidine tartrate under all lighting conditions might benefit postoperative refractive patients who report night-vision difficulties related to large pupils.

  8. Diminished activity of tartrate resistant acid phosphatase in alveolar macrophages from patients with active sarcoidosis.

    OpenAIRE

    Barth, J.; Kreipe, H.; Kiemle-Kallee, J; Radzun, H.J.; Parwaresch, M R; Petermann, W.

    1988-01-01

    Alveolar macrophages differ from their percursors in blood, monocytes, by expressing strong activity of the tartrate resistant variant of acid phosphatase (TAcP). A study was carried out to analyse the expression of this enzyme cytochemical marker by alveolar macrophages from bronchoalveolar lavage cells from 34 patients with sarcoidosis and 12 control subjects. Alveolar macrophages from control subjects displayed a strong and homogeneous staining pattern and only 0.1% of cells were negative ...

  9. CLINICAL AND ECONOMICAL ASSESSMENTS OF METOPROLOL TARTRATE/SUCCINATE USAGE IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    M. V. Soura

    2008-01-01

    Full Text Available Clinical and clinicoeconomical studies review is presented as well as results of author’s comparative cost analysis on metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK usage in patients with ischemic heart disease. Efficacy of metoprolol therapy is proven in randomized clinical studies in patients with angina and myocardial infarction (MI. In angina patients metoprolol prevents cardiac attacks, MI, reduces nitroglycerine consumption, increases exercise tolerability, prolongs the exercise time before ST segment depression (succinate better than tartrate, decrease of angina intensity. In MI patients metoprolol therapy reduces mortality, sudden death, recurring MI and the rate of early post MI angina attacks. Nowadays metoprolol is the only β-blocker having indication on secondary MI prevention. Besides for the present metoprolol succinate is the only β-blocker with proven direct antisclerosis effect. According to Swedish clinicoeconomical study in patients after MI secondary prevention with metoprolol therapy saves the costs in comparison with placebo. American clinicoeconomical model of metoprolol and atenolol usage in all patients with MI could result in significant reduction in mortality and recurring MI rate, prolong the life and improve its quality, save financial resources. The cost of monthly treatment of angina patient with metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK is 135 and 354 rubles, respectively. The price range of comparative β-blockers in ascending order is the following: atenolol (Atenolol Nicomed → metoprolol tartrate (Betaloc → metoprolol succinate (Betaloc ZOK → bisoprolol (Concor → nebivolol (Nebilet. In conclusion, metoprolol therapy is the one of mostly economically reasonable approach.

  10. Short-term effect of topical brimonidine tartrate on intrastromal corneal pressure in rabbits.

    Science.gov (United States)

    Bolívar, Gema; Teus, Miguel A; Hernández-Verdejo, José L

    2010-07-01

    Because topical brimonidine tartrate has been reported to decrease flap adherence in the early postoperative period after LASIK, its effect on the intrastromal corneal pressure (ICP) was evaluated. An interventional, prospective, animal study was performed. Intrastromal corneal pressure was recorded for 45 minutes in eight eyes of rabbits treated with topical brimonidine tartrate three times daily for 3 consecutive days (study group); eight contralateral eyes were treated with artificial tears (control group). All measurements were performed by the same, masked investigator. Mean ICP was -4.00 +/- 2.90 mmHg, -6.70 +/- 3.00 mmHg, and -9.00 +/- 4.50 mmHg at 15, 30, and 45 minutes, respectively, in the control group. In the study group (brimonidine-treated eyes), the ICP readings were +2.75 +/- 2.90 mmHg, -2.50 +/- 13.00 mmHg, and -8.50 +/- 5.00 mmHg at the same time points, respectively. The differences in the ICP between both groups were statistically significant at 15 minutes (P = .01), but no significant difference was found at 30 or 45 minutes (P = .20 and P = .80, respectively). Topical treatment with brimonidine tartrate induces a significant decrease in ICP at 15 minutes. This effect on ICP may explain the decreased corneal flap adherence reported in eyes treated with this drug.

  11. Increasing efficacy and reducing systemic absorption of brimonidine tartrate ophthalmic gels in rabbits.

    Science.gov (United States)

    Pang, Xiaochen; Li, Jiawei; Pi, Jiaxin; Qi, Dongli; Guo, Pan; Li, Nan; Wu, Yumei; Liu, Zhidong

    2017-05-31

    Systemic absorption of ocularly administered Brimonidine Tartrate has been reported to give rise to several side-effects. Hence, it has become crucial to develop a delivery system that could increase efficacy and reduce systemic absorption. Therefore, the present work aims to develop Brimonidine Tartrate gels with different concentrations (0.05%, 0.1%, and 0.2% w/v, respectively) using Carbopol 974 P and HPMC E4M, and compare the therapeutic efficacy and systemic absorption with that of eye drop (0.2%, w/v) by UPLC-MS/MS. The result of histological analysis did not show any morphological or structural changes after the administration of formulations. In vitro residence time studies demonstrated that the gels exhibited a better precorneal residence time as compared with the eye drop. The gels with lower concentrations of the drug (0.05% and 0.1%, w/v) could significantly decrease intraocular pressure (IOP) in both normal and water-loaded rabbits as compared to the eye drop. Finally, the values of the ratio of AUC(0→∞) in comparison to eye drop showed the gels with lower concentrations of Brimonidine Tartrate could decrease the systemic absorption. From the result, it can be concluded the 0.1% ophthalmic gel has a potential to improve therapeutic efficacy and reduce the potential toxicity caused by systemic absorption.

  12. COMPARISON BETAXOLOL AND METOPROLOL TARTRATE THERAPIES IN PATIENTS WITH ARTERIAL HYPERTENSION ASSOCIATED WITH STABLE ANGINA

    Directory of Open Access Journals (Sweden)

    A. A. Anderzhanova

    2016-01-01

    Full Text Available Aim. To compare antihypertensive, antianginal and antiischemic efficacy of β1-selective adrenoblockers (betaxolol and metoprolol tartrate in patients with arterial hypertension (HT of 1-2 degree associated with stable angina class II.Material and methods. 100 patients (aged 23-66 y.o. with HT associated with stable angina or without angina were involved in the study. Patients were randomized into 2 groups (G1 and G2. G1 patients were treated with betaxolol, and G2 patients – with metoprolol tartrate. Ambulatory BP and electrocardiogram monitoring, exercise stress-test, echocardiography, evaluating of respiratory function, blood analysis was performed initially and in 30 and 90 days of treatment.Results. Target BP level was reached in 44 (88% patients treated with betaxolol (average daily dose 10±4 mg. 34 patients of G1 took 10 mg daily. Target BP level was reached in 41 (82% patients treated with metoprolol tartrate (average daily dose 150±27 mg. 30 patients of G2 took 150 mg daily. Exercise tolerance increased and a number of ischemic ST segment depressions reduced significantly in both groups. There were no significant differences in antihypertensive, antianginal, and antiischemic efficacy between groups.Conclusion. Betaxolol advantage is an ability to maintain target BP level more than 24 hours. A possibility to take betaxolol once a day raises patient’s compliance with therapy.

  13. Solid-state Chemical Reaction Synthesis and Characterization of Lanthanum Tartrate Nanocrystallites Under Ultrasonication Spectra

    Science.gov (United States)

    Li, Dao-hua; He, Shao-fen; Chen, Jie; Jiang, Cheng-yan; Yang, Cheng

    2017-09-01

    Under near room temperature, by using sodium tartrate, lanthanum trichloride, lanthanum acetate, and lanthanum nitrate as reactants, we synthesize the lanthanum tartrate nanocrystals in one step under the condition that the infrared lamp is irradiated and the polyethylene glycol 400 is used as the surfactant, where the synthesis method of nanoparticles by solid phase chemical reaction is used. Deionized water after washing with ethanol washes. Tartaric acid lanthanum crystalline powder is gotten, respectively. Analyze solid products phase using X-ray diffraction (XRD) and electron diffraction; characterize the functional groups structure with infrared spectra, and analyzethe change of functional groups in drugs before and after reaction; observe the size, shape, and size distribution of particlesby transmission electron microscopy(TEM). Testing 3 types of tartaric acid crystal powder of lanthanum are nano-crystallization, solid products are granular and relatively uniform in size, with an average particle diameter of about 40 nm, and the yield rate is approximately 92.3%. Furthermore, during the synthesis, the solid-state reaction conditions including raw materials, matching proportion of reactants, additions of inert substance, addition of trace solvents, surfactants and porphyrization time, etc, all have some influence on the morphology, particle size and size distribution of the final products. During the synthesis of the lanthanum tartrate nanocrystallites, the solid state reaction conditions such as changing reactant, matching proportion of reactant, adding inert substance, joining a little solvent or surface active solvent and grinding at different times may influence morphology, particle size and the size distribution of final products.

  14. In vitro evaluation of tissue adhesives composed of hydrophobically modified gelatins and disuccinimidyl tartrate

    Directory of Open Access Journals (Sweden)

    Miyuki Matsuda

    2012-01-01

    Full Text Available The effect of the hydrophobic group content in gelatin on the bonding strength of novel tissue–penetrating tissue adhesives was evaluated. The hydrophobic groups introduced into gelatin were the saturated hexanoyl, palmitoyl, and stearoyl groups, and the unsaturated oleoyl group. A collagen casing was employed as an adherend to model soft tissue for the in vitro determination of bonding strength of tissue adhesives composed of various hydrophobically modified gelatins and disuccinimidyl tartrate. The adhesive composed of stearoyl-modified gelatin (7.4% stearoyl; 10Ste and disuccinimidyl tartrate showed the highest bonding strength. The bonding strength of the adhesives decreased as the degree of substitution of the hydrophobic groups increased. Cell culture experiments demonstrated that fluorescein isothiocyanate-labeled 10Ste was integrated onto the surface of smooth muscle cells and showed no cytotoxicity. These results suggest that 10Ste interacted with the hydrophobic domains of collagen casings, such as hydrophobic amino acid residues and cell membranes. Therefore, 10Ste–disuccinimidyl tartrate is a promising adhesive for use in aortic dissection.

  15. COMPARISON BETAXOLOL AND METOPROLOL TARTRATE THERAPIES IN PATIENTS WITH ARTERIAL HYPERTENSION ASSOCIATED WITH STABLE ANGINA

    Directory of Open Access Journals (Sweden)

    A. A. Anderzhanova

    2009-01-01

    Full Text Available Aim. To compare antihypertensive, antianginal and antiischemic efficacy of β1-selective adrenoblockers (betaxolol and metoprolol tartrate in patients with arterial hypertension (HT of 1-2 degree associated with stable angina class II.Material and methods. 100 patients (aged 23-66 y.o. with HT associated with stable angina or without angina were involved in the study. Patients were randomized into 2 groups (G1 and G2. G1 patients were treated with betaxolol, and G2 patients – with metoprolol tartrate. Ambulatory BP and electrocardiogram monitoring, exercise stress-test, echocardiography, evaluating of respiratory function, blood analysis was performed initially and in 30 and 90 days of treatment.Results. Target BP level was reached in 44 (88% patients treated with betaxolol (average daily dose 10±4 mg. 34 patients of G1 took 10 mg daily. Target BP level was reached in 41 (82% patients treated with metoprolol tartrate (average daily dose 150±27 mg. 30 patients of G2 took 150 mg daily. Exercise tolerance increased and a number of ischemic ST segment depressions reduced significantly in both groups. There were no significant differences in antihypertensive, antianginal, and antiischemic efficacy between groups.Conclusion. Betaxolol advantage is an ability to maintain target BP level more than 24 hours. A possibility to take betaxolol once a day raises patient’s compliance with therapy.

  16. Effects of Alprazolam, Zolpidem and Zopiclone, and of chronic inflammation on peripheral experimental algesia in Wistar rats.

    Science.gov (United States)

    Zdrîncă, Mihaela; Muţiu, Gabriela; Bogdan, Maria; Dobjanschi, Luciana; Antonescu, Angela; Moş, Ioana; Mureşan, Mariana; Zdrîncă, M; Antonescu, Andreea

    2011-01-01

    In the literature, there are some data which indicate that benzodiazepines and other chemical compounds with the same mechanism of action (Diazepam, Chlordiazepoxide, Lorazepam, Zopiclone, etc.) also have other effects. We investigated the effects of experimental chronic inflammation under the administration of some tranquilizers and hypnotics on peripheral algesia induced in rats by "writhing test". Chronic inflammation was induced by "cotton wool granuloma" technique. The "writhing test" consisted in intraperitoneal injection of an irritant agent (acetic acid 0.0025%, 0.4 mL). The animal reacts with a characteristic stretching behavior called writhing. A writhe is indicated by stretching of the abdomen with simultaneous stretching of at least one hind limb. Then, the animals were placed individually into glass beakers and 5 minutes were allowed to elapse. The rats were then observed for a period of 10 minutes and the number of writhes is recorded for each animal. Three drugs were administered by gastric probe: Alprazolam 1 mg/kg, Zolpidem 10 mg/kg and Zopiclone 10 mg/kg. Alprazolam is a triazolobenzodiazepine derivative used as a tranquilizer. Zolpidem is an imidazopyridine with marked sedative-hypnotic effect and it has the same mechanism of action like benzodiazepines. Zopiclone is a cyclopyrrolone with sedative-hypnotic effect used as hypnotic and acts like benzodiazepines. After that, the animals were sacrificed and the weight of cotton wool granuloma was determined. In the same time, the histopatological aspect of granulomatous inflammation was studied. It was found that experimental proliferative inflammation under the action of these drugs was accompanied by a peripheral analgesic activity in "writhing test". The mechanisms of these effects are not fully elucidated. Some explanations are: they act as agonists or antagonists on algesia and inflammation mediators and they have a stimulating effect on peripheral ω3-benzodiazepine receptors ("peripheral

  17. 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

  18. 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

  19. 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

  20. 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...

  1. 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.

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

    Science.gov (United States)

    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.

  3. 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.

  4. 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

  5. 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.)

  6. 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...

  7. 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

  8. 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.

  9. 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)

  10. 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

  11. A validated stability-indicating HPLC method for determination of brimonidine tartrate in BRI/PHEMA drug delivery systems.

    Science.gov (United States)

    Sun, Jianguo; Zhang, Xiuwen; Huang, Taomin

    2017-07-11

    A simple, rapid and accurate stability-indicating reverse phase high performance liquid chromatography (RP-HPLC) was developed and validated for the determination of brimonidine tartrate in brimonidine tartrate/poly(2-hydroxyethyl methacrylate) (BRI/PHEMA) drug delivery contact lenses and pharmaceutical formulations. Optimum chromatographic conditions for separating brimonidine tartrate from other impurities in the leaching liquor of BRI/PHEMA drug delivery contact lenses or pharmaceutical formulations have been achieved by using a Diamonsil C18 column (150 mm × 4.6 mm, 5 μm) as a stationary phase and a mixture solution of phosphate buffer (10 mM, pH3.5) containing 0.5% triethlamine and methanol (85:15, v/v) as a mobile phase at a flow rate of 1 mL/min. The theoretical plates for the brimonidine tartrate measurement were calculated to be 8360 when detection was performed at 246 nm using a diode array detector. The proposed method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, robustness, specificity, limit of detection and quantitation. Regression analysis showed a good correlation (R2 > 0.999) for brimonidine tartrate in the concentration range of 0.01-50 μg/mL. The peak purity factor is ≥980 for the analyte after all types of stress tests, indicating an excellent separation of brimonidine tartrate peak from other impurities. The measurement course could be completed within 10 min, which was very quick, effective and convenient. Overall, the proposed stability-indicating method was suitable for routine quality control and drug analysis of brimonidine tartrate in BRI/PHEMA drug delivery contact lenses and other pharmaceutical formulations.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Effect of brimonidine tartrate 0.15% on scotopic pupil: controlled trial.

    Science.gov (United States)

    Gerente, Vanessa M; Biondi, Adriano C; Barbosa, Carolina P; Lottenberg, Claudio L; Paranhos, Augusto

    2007-10-01

    The aim of this study was to evaluate the duration of the effect of one single dose of brimonidine tartrate 0.15% on pupil diameter, under scotopic conditions, when applied topically in 1 eye of normal subjects. The eyes of 19 normal volunteers were randomized so that 1 eye had 1 drop of brimonidine tartrate 0.15% and the other received no medication. Pupil diameter was measured using an infrared pupillometer. The first measure was obtained before the instillation of brimonidine. After that, four measures, with 2-h intervals, were performed. From 19 participants, 14 were women and 5 were men, with a mean age of 25.05 years (standard deviation, +/- 6.98). Before brimonidine instillation, mean pupil diameter in the control eyes was 5.11 mm, and in the brimonidine eyes it was 5.15 mm. After 8 h, the mean pupil size was 4.01 mm in the treated eyes, and 4.56 mm in the untreated eyes. There was a tendency of miotic effect to be more important on the treated eye, as compared to the control eye in all intervals, but this did not reach statistical significance (P = 0.375). When comparing both eyes, independently of the periods, the treated eye had a smaller diameter than the untreated eye (P = 0.038). The miotic effect was observed for at least 8 h after instillation. Miotic response of brimonidine tartrate 0.15% lasted for at least 8 h and has a significant effect on the nontreated eye.

  17. Enantioselective toxicities of chiral ionic liquids 1-alkyl-3-methyl imidazolium tartrate on Scenedesmus obliquus.

    Science.gov (United States)

    Liu, Huijun; Zhang, Xiaoqiang; Dong, Ying; Chen, Caidong; Zhu, Shimin; Ma, Xiangjuan

    2015-12-01

    Ionic liquids (ILs) are being used in various industries during the last few decades, while the good solubility and high stability of ILs may pose a potential threat to the aquatic environment. Effect of chiral ionic liquids (CILs) 1-alkyl-3-methyl imidazolium tartrate (RMIM T) on Scenedesmus obliquus (S.obliquus) was studied. The growth rate inhibition and cell membrane permeability increased with increasing RMIM T concentration and increasing alkyl chain lengths. The IC50 values of D-(-)-tartrate 1-hexyl-3-methyl imidazolium (D-(-)-HMIM T) were 28.30, 12.23,10.15 and 14.41 mg/L, respectively, at 24, 48, 72 and 96h. While that of L-(+)-tartrate 1-hexyl-3-methyl imidazolium (L-(+)-HMIM T) were 15.97, 7.91, 9.43 and 12.04 mg/L respectively. The concentration of chl a, chl b and chl (a+b) decreased with increasing RMIM T concentration. The chlorophyll fluorescence parameters (F0, Fv/Fm, Fv/F0, Y(II), ETR and NPQ) were affected by RMIM T, indicating that the RMIM T will damage the PSII, inhibit the transmission of excitation energy, decrease the efficiency of photosynthesis. The results showed that there were enantioselective toxicity of RMIM T to algae, and the toxicity of L-(+)-RMIM T was greater than that of D-(-)-RMIM T, but the enantioselective difference becomes smaller with increasing exposure time, and with the increasing carbon chain length of cation, indicating that cation properties may have a larger effect on toxicity than anion properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 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

  19. Tartrate-resistant acid phosphatase as a differentiation marker for the human mononuclear phagocyte system.

    Science.gov (United States)

    Radzun, H J; Kreipe, H; Parwaresch, M R

    1983-01-01

    Human blood monocytes (BM) were stimulated with various immune modulators in short-term cultures. Tartrate-resistant acid phosphatase (TAcP) activity was demonstrated with an enzyme cytochemical method. Other members of the mononuclear phagocyte system (MPS), such as peritoneal (PM) and alveolar macrophages (AM), were also tested. Unstimulated BM and physiologic functional forms of macrophages, with the exception of AM, were invariably TAcP negative. On appropriate stimulation, particularly with media containing lymphokines, cultured BM became TAcP positive. The results suggest that TAcP is an inducible differentiation marker that indicates transformation of monocytes into cells belonging to a distinct subset of the MPS.

  20. Clinical potential of eliglustat tartrate in the treatment of type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Kaplan P

    2014-05-01

    Full Text Available Paige KaplanLysosomal Disorders Center, Section of Metabolic Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USAAbstract: Nonneuropathic type 1 Gaucher disease is an autosomal recessive inherited disease caused by the deficiency or absence of beta glucocerebrosidase (beta glucosidase. The highest prevalence of type 1 is in Ashkenazi Jews, but it affects all ethnic groups. It manifests at any age but is seen predominantly in the first two decades. The phenotype is characterized by painless splenomegaly and secondary hypersplenism (low hemoglobin concentration and low platelet and white blood cell counts. Symptoms and signs include splenomegaly; chronic fatigue, frequent nose bleeds, prolonged bleeding, and/or bruising; hepatomegaly; bone pain, bone destruction and low bone density; and poor growth in childhood and delayed pubertal development. Current treatment with intravenous enzyme replacement has been generally successful. However, oral treatments have been developed because enzyme replacement is time-consuming and invasive, and intravenous infusions are not universally available for patients who live far from medical centers or home infusion nurses. Furthermore, it may become difficult to access veins after repeated infusions. Orally administered substrate reduction is a newer treatment approach. The aim is to limit the synthesis of the substrate, glucosylceramide. The residual intrinsic enzyme, acting alone or with recombinant enzyme, can then completely catabolize the smaller amounts of glucosylceramide that are transported into lysosomes. Eliglustat tartrate is a new specific inhibitor of glucosylceramide synthase. Phase III trials in humans have been completed. Eliglustat tartrate has been shown to be efficacious and safe in adult humans. The results are as good or better compared with intravenous replacement with regard to reductions in spleen and liver enlargement and improvements in hemoglobin concentrations, platelet

  1. Effect of brimonidine tartrate 0.15% on night-vision difficulty and contrast testing after refractive surgery.

    Science.gov (United States)

    Edwards, Jayson D; Burka, Jenna M; Bower, Kraig S; Stutzman, Richard D; Sediq, Denise A; Rabin, Jeff C

    2008-09-01

    To evaluate the efficacy of brimonidine tartrate ophthalmic solution 0.15% in patients with night-vision difficulties after laser refractive surgery. Center for Refractive Surgery, Walter Reed Army Medical Center, Washington, District of Columbia, USA. Six patients with significant night-vision complaints after refractive surgery were enrolled in this study after other treatable causes of night-vision difficulty such as residual refractive error and dry eye were excluded. Low-contrast visual acuity (LCVA) over a range of contrasts (1.25% to 25%) and small letter contrast sensitivity were tested at photopic (100 cd/m(2)) and mesopic (1 cd/m(2)) luminance levels, with and without a standard glare source. Testing was performed before brimonidine tartrate ophthalmic solution 0.15% was administered. Measurements were repeated 1 hour and 1 month after the use of brimonidine tartrate. One hour after using brimonidine tartrate 0.15% solution, patients had significant improvement in LCVA, LCVA with glare, and contrast sensitivity. After 1 month of treatment, all 6 patients reported subjective improvement in night vision and there was a significant difference in performance in mesopic LCVA and mesopic LCVA with glare. The mean pupil size before administration of brimonidine tartrate ophthalmic solution 0.15% was 6.44 mm +/- 1.11 (SD). Pupil size 1 hour after instillation had decreased to 4.53 +/- 1.27 mm and at 1 month had increased to 6.50 +/- 0.94 mm. Brimonidine tartrate ophthalmic solution 0.15% improved contrast sensitivity and acuity and decreased night-vision difficulty for up to 1 month in patients with significant complaints after refractive surgery.

  2. New, Occasional, and Frequent Use of Zolpidem or Zopiclone (Alone and in Combination) and the Risk of Injurious Road Traffic Crashes in Older Adult Drivers: A Population-Based Case-Control and Case-Crossover Study.

    Science.gov (United States)

    Nevriana, Alicia; Möller, Jette; Laflamme, Lucie; Monárrez-Espino, Joel

    2017-08-01

    Previous studies on the effect of zolpidem or zopiclone use on the risk of road traffic crashes (RTCs) have shown mixed results. Our objective was to determine the association between zolpidem or zopiclone use (as separate drugs or combined) and the occurrence of injurious RTCs among older adult drivers. This was a population-based matched case-control and case-crossover study based on secondary data linked together from Swedish national registers. Cases were drivers aged 50-80 years involved in a vehicle crash resulting in injuries between January 2006 and December 2009 for the case-control study (n = 27,096) and from February 2006 to December 2009 for the case-crossover study (n = 26,586). For the first design, four controls were matched to each case by sex, age, and residential area, and exposure was categorized into new, occasional, and frequent use of zolpidem only, zopiclone only, and combined zolpidem and zopiclone. For the case-crossover study, newly dispensed zolpidem or zopiclone users were assessed during the 28 days prior to the crash and compared with an equally long control period using a 12-week washout period. Matched adjusted odds ratios (OR) were computed using conditional logistic regression. Increased ORs for all users were observed. In the case-control study, the highest odds were seen among newly initiated zolpidem-only users involved in single-vehicle crashes (adjusted OR 2.27; 95% confidence interval [CI] 1.21-4.24), followed by frequent combined zolpidem and zopiclone users [adjusted OR 2.20; CI 1.21-4.00]. In the case-crossover, newly initiated treatment with zolpidem or zopiclone showed an increased risk that was highest in the 2 weeks after the start of the treatment (OR 2.66; 95% CI 1.04-6.81). These results provide more compelling evidence for the role of zolpidem or zopiclone in the occurrence of RTCs among older adults, not only in frequent users, but also at the beginning of treatment.

  3. Multidrug comparison (lorazepam, triazolam, zolpidem, and zopiclone) in situational insomnia: polysomnographic analysis by means of the cyclic alternating pattern.

    Science.gov (United States)

    Parrino, L; Boselli, M; Spaggiari, M C; Smerieri, A; Terzano, M G

    1997-06-01

    Since homogeneous samples of insomniacs are difficult to recruit for pharmacotherapy studies, normal sleepers can be used to assess the protective effect of hypnotic drugs, under standardized nonconducive conditions. In particular, a noisy environment is a typical cause of situational insomnia that can be counteracted by a sedative-hypnotic agent. Six healthy middle-aged subjects (three men and three women), with no complaints about sleep, underwent a completely randomized double-blind series of 10 nocturnal polysomnograms with at least 72-h washout intervals. All subjects received a single dose of placebo, zolpidem 10 mg, zopiclone 7.5 mg, lorazepam 1 mg, and triazolam 0.25 mg both under basal and under perturbed conditions. For each individual, five recordings were carried out under basal conditions (sound pressure level not higher than 30 dB) and five recordings under acoustically perturbed conditions (continuous white noise at 55 dB). Sleep quality was assessed by means of a visual analogue scale (VAS). All recordings were scored according to conventional rules (macro-structure) and cyclic alternating pattern (CAP) methodology (microstructure). Statistical analysis was based on a repeated measures analysis-of-variance design integrated by Bonferroni adjusted probabilities. Under placebo, situational insomnia was confirmed by the significant increase in sleep fragmentation (intrasleep wakefulness) and by the significant enhancement of arousal instability (CAP parameters). In contrast to macrostructural information, CAP parameters were highly sensitive in detecting the perturbing effects of noise (mean CAP rate under placebo, 57%) and the protective action of hypnotic drugs during perturbation (mean CAP rate under active medication, 41%). Microstructural analysis enabled us to discriminate hypnotic drugs from placebo, nonbenzodiazepine compounds from benzodiazepine agents, and zopiclone from zolpidem. The latter, in fact, induced the lowest values of CAP rate

  4. Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson’s Disease? The Potential Role of Zolpidem in the Treatment of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Antonio Daniele

    2016-01-01

    Full Text Available At present, patients with advanced Parkinson’s disease (PD are unsatisfactorily controlled by currently used anti-Parkinsonian dopaminergic drugs. Various studies suggest that therapeutic strategies based on nondopaminergic drugs might be helpful in PD. Zolpidem, an imidazopyridine widely used as sleep inducer, shows high affinity only for GABAA receptors containing the α-1 subunit and facilitates GABAergic neurotransmission through a positive allosteric modulation of GABAA receptors. Various observations, although preliminary, consistently suggest that in PD patients zolpidem may induce beneficial (and sometimes remarkable effects on motor symptoms even after single doses and may also improve dyskinesias. Since a high density of zolpidem binding sites is in the two main output structures of the basal ganglia which are abnormally overactive in PD (internal globus pallidus, GPi, and substantia nigra pars reticulata, SNr, it was hypothesized that in PD patients zolpidem may induce through GABAA receptors an inhibition of GPi and SNr (and, possibly, of the subthalamic nucleus also, resulting in an increased activity of motor cortical areas (such as supplementary motor area, which may give rise to improvement of motor symptoms of PD. Randomized clinical trials are needed in order to assess the efficacy, safety, and tolerability of zolpidem in treating motor symptoms of PD.

  5. 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...

  6. 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

  7. 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...

  8. Preparation and Evaluation of Nano-vesicles of Brimonidine Tartrate as an Ocular Drug Delivery System.

    Science.gov (United States)

    Prabhu, P; Nitish, Kumar R; Koland, M; Harish, Nm; Vijayanarayan, K; Dhondge, G; Charyulu, Rn

    2010-10-01

    The objective of the present investigation was to design a vesicular formulation of brimonidine tartrate and evaluate its ability to reduce the dosing frequency and improve the therapeutic efficacy of the drug. Nano-vesicles of brimonidine tartrate were prepared by film hydration method. The prepared vesicles were evaluated for photomicroscopic characteristics, entrapment efficiency, in vitro, and ex-in vitro drug release and in vivo intraocular pressure (IOP) lowering activity. The methods employed for preparation of vesicles produced nano vesicles of acceptable shape and size. The in vitro, and ex-in vitro drug release studies showed that there was slow and prolonged release of the drug, which followed zero-order kinetics. The IOP-lowering activity of nano vesicles was determined and compared with that of pure drug solution and showed that the IOP-lowering action of nano-vesicles sustained for a longer period of time. Stability studies revealed that the vesicle formulations were stable at the temperature range of 2-8°C, with no change in shape and drug content. The results of the study indicate that it is possible to develop a safe and physiologically effective topical formulation that is also convenient for patients.

  9. 1,10-Phenanthrolin-1-ium hydrogen (S,S-tartrate trihydrate and a correction

    Directory of Open Access Journals (Sweden)

    Zohreh Derikvand

    2010-01-01

    Full Text Available The title structure, C12H9N2+·C4H5O6−·3H2O, shows that one of the protons of d-tartaric acid has been transferred to 1,10-phenanthroline. The d-hydrogen tartrate anions are joined together in a head-to-tail fashion via a short hydrogen bond with donor–acceptor distance of 2.4554 (12 Å, unsymmetrical O—H distances of 1.01 (4 Å and 1.45 (4 Å, and a 174 (4° O—H—O bond angle. The phenanthrolinium rings are π-stacked with an average separation of 3.58 (11 Å. The structural report corrects a previous report in the literature [Wang et al. (2006. Acta Cryst. E62, o2508–o2509] of the isostructural l-hydrogen tartrate enantiomer in which the proton transfer and short hydrogen bond were missed.

  10. Formulation and in vitro evaluation of fast dissolving tablets of metoprolol tartrate

    Directory of Open Access Journals (Sweden)

    Mangesh Machhindranath Satpute

    2013-12-01

    Full Text Available The demand for fast dissolving tablets has been growing during the last decade, especially for elderly and children who have swallowing difficulties. In the present work, fast dissolving tablets of metoprolol tartrate, were prepared using sodium starch glycolate, sodium croscarmellose and crospovidone as superdisintegrants, by the direct compression method. The tablets prepared were evaluated for various parameters including weight variation, hardness, friability, in vitro dispersion time, drug-polymer interaction, drug content water absorption ratio, wetting time, in vitro drug release, FTIR and DSC studies. The tablets prepared by the direct compression method had a weight variation in the range of 145 mg to 152 mg, which is below ± 7.5%, a hardness of 3.6 kg/cm² to 4.5 kg/cm², percentage friability of 0.46% to 0.73%, in vitro dispersion time of 18 s to 125 s, drug content uniformity of between 98.12% and 100.03%, a water absorption ratio of 67% to 87%, wetting time of 32 sec. to 64 sec., and an in vitro drug release of 53.92% - 98.82% within 15 min. The IR spectral analysis and DSC study showed no drug interaction with formulation additives of the tablet, and the formulations indicated no significant changes in hardness, friability, drug content or in vitro drug release. Fast dissolving tablets of metoprolol tartrate have enhanced dissolution and will lead to improved bioavailability and more effective therapy.

  11. Bis(tetra-ethyl-ammonium) bis-(hydrogen l-tartrate) l-tartaric acid monohydrate.

    Science.gov (United States)

    Rajalakshmi, M; Indirajith, R; Gopalakrishnan, R; Ramamurthi, K; Stoeckli-Evans, Helen

    2011-06-01

    In the title compound, 2C(8)H(20)N(+)·2C(4)H(5)O(6) (-)·C(4)H(6)O(6)·H(2)O, the presence of the two tetra-ethyl-ammonium cations is balanced by two hydrogen l-tartrate anions. Also present in the asymmetric unit are a mol-ecule of l-tartaric acid and a water mol-ecule. The various components are linked by O-H⋯O hydrogen bonds. In the crystal, two-dimensional networks are formed via O-H⋯O hydrogen bonds and C-H⋯O inter-actions involving the water mol-ecule, the hydrogen l-tartrate anions and the l-tartaric acid mol-ecules. These layers, which stack along [001], are separated by tetra-ethyl-ammonium cations. The latter are also involved in C-H⋯O inter-actions with the anions and the l-tartaric acid and water mol-ecules participating in the two-dimensional network.

  12. A Black Phosphate Conversion Coating on Steel Surface Using Antimony(III)-Tartrate as an Additive

    Science.gov (United States)

    Li, Feng; Wang, Guiping

    2016-05-01

    A novel black phosphate conversion coating was formed on steel surface through a Zn-Mn phosphating bath containing mainly ZnO, H3PO4, Mn(H2PO4)2, and Ca(NO3)2, where antimony(III)-tartrate was used as the blackening agent of phosphatization. The surface morphology and composition of the coating were characterized by scanning electron microscopy, energy dispersion spectroscopy, and x-ray photoelectron spectroscopy. Corrosion resistance of the coating was studied by potentiodynamic polarization curves and electrochemical impedance spectroscopy. The pH value of the solution had significant influence on the formation and corrosion resistance of the coating. The experimental results indicated that the Sb plays a vital role in the blackening of phosphate conversion coating. The optimal concentration of antimony(III)-tartrate in the phosphating bath used in this experiment was 1.0 g L-1, as higher values reduced the corrosion resistance of the coating. In addition, by saponification and oil seals, the corrosion duration of the black phosphate coating in a copper sulfate spot test can be as long as 20 min.

  13. Eliglustat tartrate for the treatment of adults with type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Bennett LL

    2015-08-01

    Full Text Available Lunawati L Bennett, Kelsey TurcotteSchool of Pharmacy, Union University, Jackson, TN, USA Abstract: The purpose of this article is to review eliglustat tartrate, a substrate reduction therapy, for the treatment of Gaucher disease type 1 (GD1. GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia. GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3 which are more progressive diseases with no approved drugs available at this time. Treatment options for GD1 include enzyme replacement therapy and substrate reduction therapy. Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome. Eliglustat was approved by the US Food and Drug Administration after three Phase I, two Phase II, and two Phase III clinical trials. The dose of eliglustat is 84 mg twice a day or once daily depending on the cytochrome P450 2D6 genotype of the patient. Keywords: Gaucher disease, glucocerebrosidase, glucosylceramide synthase, eliglustat tartrate, substrate reduction therapy

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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...

  19. 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

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

    Science.gov (United States)

    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.

  1. 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...

  2. 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.

  3. [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.

  4. 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.

  5. 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.

  6. 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.

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

    Science.gov (United States)

    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

  8. 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

  9. 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

  10. 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....

  11. Diminished activity of tartrate resistant acid phosphatase in alveolar macrophages from patients with active sarcoidosis.

    Science.gov (United States)

    Barth, J; Kreipe, H; Kiemle-Kallee, J; Radzun, H J; Parwaresch, M R; Petermann, W

    1988-11-01

    Alveolar macrophages differ from their percursors in blood, monocytes, by expressing strong activity of the tartrate resistant variant of acid phosphatase (TAcP). A study was carried out to analyse the expression of this enzyme cytochemical marker by alveolar macrophages from bronchoalveolar lavage cells from 34 patients with sarcoidosis and 12 control subjects. Alveolar macrophages from control subjects displayed a strong and homogeneous staining pattern and only 0.1% of cells were negative after staining. Macrophages from patients with sarcoidosis showed reduced TAcP activity and up to 7% of the cells were negative. The percentage of TAcP negative macrophages was correlated with the percentage of lymphocytes and with the ratio of CD4 to CD8 lymphocytes among cells recovered by bronchoalveolar lavage. The reduced TAcP activity in alveolar macrophages from patients with sarcoidosis may be due to an increased recruitment of immature precursors from blood.

  12. Transdermal delivery of tolterodine tartrate for overactive bladder treatment: In vitro and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Rajabalaya Rajan

    2017-09-01

    Full Text Available The purpose of the study was to develop a transdermal tolterodine tartrate (TT patch and to analyse its efficacy for overactive bladder (OAB treatment. Patches were prepared using various polymers and plasticizers via the solvent casting method. The patches were characterized for tensile strength, thickness, moisture content, modulus of elasticity and water absorption capacity. Differential scanning calorimetry and Fourier transform infrared analyses were also performed. To determine patch effectiveness, in vitro release, permeation and animal studies were performed. The patches showed satisfactory percentage of release, up to 89.9 %, and their mechanical properties included thickness (0.10–0.15 mm, tensile strength (4.62–9.98 MPa and modulus of elasticity (20–29 MPa. There were no significant interactions between TT and other excipients. Animal studies indicated that the TT patch reduced the incidence of side effects; however, studies of longer duration are required to determine the effectiveness in treating OAB.

  13. Removal of Pb{sup 2+} from the aqueous solution by tartrate intercalated layered double hydroxides

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Yanming; Zhao, Xiaolei; Zhang, Xi; Li, Shifeng; Liu, Dongbin; Fan, Lihui [Shenyang University of Chemical Technology, Shenyang (China)

    2016-01-15

    Adsorption of Pb{sup 2+} ion by a tartrate intercalated MgAl layered double hydroxides (MgAl-TA LDHs) was studied. The adsorption isotherms and kinetics were investigated as a function of various experimental parameters using batch adsorption experiments. The results indicated that the adsorption isotherm was well described by Sips model. The kinetic adsorption data were fitted well to the pseudo-second-order kinetic equation. The adsorption of Pb{sup 2+} was controlled mainly by the chemical process combined with intraparticle diffusion. Parameters of adsorption thermodynamic suggested that the interaction of Pb{sup 2+} adsorbed by MgAl-TA LDHs adsorbents was thermodynamically spontaneous and endothermic.

  14. Spectrophotometric Determination of Metoprolol Tartrate in Pharmaceutical Dosage Forms on Complex Formation with Cu(II

    Directory of Open Access Journals (Sweden)

    Mustafa Cesme

    2011-06-01

    Full Text Available A new, simple, sensitive and accurate spectrophotometric method has been developed for the assay of metoprolol tartrate (MPT, which is based on the complexation of drug with copper(II [Cu(II] at pH 6.0, using Britton-Robinson buffer solution, to produce a blue adduct. The latter has a maximum absorbance at 675 nm and obeys Beer’s law within the concentration range 8.5-70 mg/mL. Regression analysis of the calibration data showed a good correlation coefficient (r = 0.998 with a limit of detection of 5.56 mg/mL. The proposed procedure has been successfully applied to the determination of this drug in its tablets. In addition, the spectral data and stability constant for the binuclear copper(II complex of MPT (Cu2MPT2Cl2 have been reported.

  15. Crystal structure of (S)-sec-butyl-ammonium l-tartrate monohydrate.

    Science.gov (United States)

    Publicover, Ernlie A; Kolwich, Jennifer; Stack, Darcie L; Doué, Alyssa J; Ylijoki, Kai E O

    2017-05-01

    The title hydrated mol-ecular salt, C4H12N+·C4H5O6-·H2O, was prepared by deprotonation of enanti-opure l-tartaric acid with racemic sec-butyl-amine in water. Only one enanti-omer was observed crystallographically, resulting from the combination of (S)-sec-butyl-amine with l-tartaric acid. The sec-butyl-ammonium moiety is disordered over two conformations related by rotation around the CH-CH2 bond; the refined occupancy ratio is 0.68 (1):0.32 (1). In the crystal, mol-ecules are linked through a network of O-H⋯O and N-H⋯O hydrogen-bonding inter-actions, between the ammonium H atoms, the tartrate hy-droxy H atoms, and the inter-stitial water, forming a three-dimensional supra-molecular structure.

  16. Sedative and physiological effects of brimonidine tartrate ophthalmic solution in healthy cats.

    Science.gov (United States)

    Ogata, Niwako; Kanda, Teppei; Kawahata, Mizuki; Ichikawa, Takayasu; Matsumoto, Yuki; Morimitsu, Waka; Nishino, Yukiko; Itoi, Takamasa; Furumoto, Kayo

    2017-09-01

    To determine the effects of brimonidine tartrate ophthalmic solution on sedation, heart rate (HR), respiratory frequency (fR), rectal temperature (RT) and noninvasive mean arterial pressure (MAP) in healthy cats. Randomized, blinded crossover study, with 1 week washout between treatments. Six healthy purpose-bred cats. Brimonidine tartrate ophthalmic solution 0.1% (one or two drops; 58.6 ± 3.3 μg per drop) or a control solution (artificial tear solution) was administered to six healthy cats. Behavioural observations and measurements of HR, fR, RT and MAP were recorded before and at 30, 60, 90, 120, 180, 240, 300 and 360 minutes after topical administration. Behavioural scores were analysed using Friedman's test for repeated measures to evaluate the time effect in each treatment and treatment effect at each time point. Physiological variables (HR, fR, RT and MAP) were analysed using two-way analysis of variance for repeated measures to evaluate the time and treatment effects. The level of significance was set at p brimonidine resulted in sedation in the cats and decreased HR and MAP. Significant sedative effects occurred between 30 and 120 minutes and for physiological responses up to 360 minutes. The most frequent adverse reaction was vomiting, occurring within 40 minutes in all six cats administered two drops and five of the six cats administered one drop of brimonidine. The results demonstrated that ocular administration of brimonidine 0.1% ophthalmic solution induced sedation in cats and some cardiovascular effects usually associated with α2-adrenoceptor agonists. Further studies should be performed to determine clinical applications for this agent in cats. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  17. Chick chorioallantoic membrane model for in ovo evaluation of timolol maleate-brimonidine tartrate ocular inserts.

    Science.gov (United States)

    Ravindran, Vinod Kombath; Repala, Swathi; Subadhra, Sandhya; Appapurapu, Ashok Kumar

    2014-06-01

    The main aspire of this study was to develop ocular drug delivery system for dual drug glaucoma therapy by timolol maleate-brimonidine tartrate and endeavor the possibility of biocompatibility studies by in ova studies. Matrix type, both hydrophilic and lipophilic polymers, and reservoir-type ocular inserts of timolol maleate were prepared using hydrophilic polymers like polyvinyl alcohol, hydroxyl propyl methyl cellulose K4M and lipophilic polymers like ethylcellulose and eudragit S100 and were optimized. Based on the optimized formulation, triple-layered ocular inserts (reservoir type) of dual drug were prepared by solvent casting technique with an objective of reducing the frequency of administration, obtaining controlled release and greater therapeutic efficacy, preservative free dosage form for the treatment of glaucoma. FTIR spectral studies revealed no pharmaceutical incompatibility and no drug polymer interactions. Maximum drug release (99.18 ± 1.7) was achieved when PVP and HPMC K4M in 1:1 ratio with PEG 400 (0.3 ml) drug reservoir layer was sandwiched between ethyl cellulose as rate control membrane up to 32 h in a controlled fashion. Drug release was by non-Fickian diffusion mechanism for single drug formulation. But in dual drug insert, timolol maleate best fit into zero order and for brimonidine tartrate to Higuchi model and diffusion of drugs from this by non-Fickian diffusion mechanism. In ovo studies suggested that the optimized formulation was found to be sterile, biocompatible and physicochemically stable and support us to claim that the developed formulation was biocompatible.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. 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...

  8. Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat

    DEFF Research Database (Denmark)

    Kiss, Alexander; Søderman, Andreas; Bundzikova, Jana

    2006-01-01

    Functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei was investigated in response to acute treatment with Zolpidem (a GABA(A) receptor agonist with selectivity for alpha(1) subunits) utilizing dual Fos/OXY immun...

  9. EFFICACY OF TYLOSIN TARTRATE ON MYCOPLASMA INFECTIONS AND EGGSHELL APEX ABNORMALITIES IN LAYER HENS UNDER FIELD CONDITIONS

    OpenAIRE

    Konstantinos C. Koutoulis; George Kefalas; Niki Mouttotou; Koen De Gussem; Dimitris Theodosiou

    2013-01-01

    The aim of this report was to describe a clinical case of concurrent infection with Mycoplasma Gallisepticum (MG) and Mycoplasma Synoviae (MS) in layers, complicated with Escherichia coli and Pasteurella multocida, as well as to evaluate the efficacy of tylosin tartrate treatment (Pharmasin® 100% WSG, Huvepharma) on Mycoplasma under field conditions. A flock of 18,500 ISA Brown pullets, 21 weeks of age and MS positive, showed an increase in weekly mortality, with no influence on egg producti...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

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

    Science.gov (United States)

    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

  15. Phase selection during the crystallization of metal-organic frameworks; thermodynamic and kinetic factors in the lithium tartrate system.

    Science.gov (United States)

    Yeung, Hamish Hei-Man; Cheetham, Anthony Kevin

    2014-01-07

    We report the phase behaviour of chiral, racemic and meso-lithium tartrate frameworks, which was examined as a function of solvent system, temperature and ligand isomer. Through our comprehensive investigation of this system of 14 diverse phases, we have gained detailed insight into the effect of synthesis conditions on product structure, and elucidated the thermodynamic and kinetic factors involved in phase selection. Reactions in ethanol between lithium acetate and chiral, racemic and meso-tartaric acids give rise to anhydrous kinetic products; polymorphs with higher entropy tend to appear at high temperatures. Reactions at room temperature in water-ethanol mixtures give rise to hydrated kinetic products, including two new crystal structures, [Li2(D,L-tartrate)(H2O)2]n in P1 and [Li2(meso-tartrate)(H2O)(0.5)]n in C222(1), whose structures are contrasted with known anhydrous products. Reactions at elevated temperatures in water-ethanol mixtures result in the formation of low enthalpy, anhydrous products and, furthermore, the global minimum energy structure appears at high temperatures in all cases owing to in situ ligand isomerization.

  16. 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.

  17. 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

  18. Separation of corticosteroids by microemulsion EKC with diethyl L-tartrate as the oil phase.

    Science.gov (United States)

    Wu, Chi-Hung; Chen, Tse-Hsien; Huang, Kuan-Pin; Wang, Guan-Ren; Liu, Chuen-Ying

    2007-10-01

    A novel microemulsion based on a mixture of diethyl L-tartrate (DET) and SDS was developed for the microemulsion EKC (MEEKC) determination of structurally related steroids. The system consisted of 0.5% w/w DET, 1.7% w/w SDS, 1.2% w/w 1-butanol, 89.6% w/w phosphate buffer (40 mM, pH 7.0), and 7% w/w ACN. With an applied voltage of +10 kV, a baseline separation of aldosterone (A), cortisone acetate (CA), dexamethasone (D), hydrocortisone (H), hydrocortisone acetate (HA), prednisolone (P), prednisolone acetate (PA), prednisone (Ps), triamcinolone (T), and triamcinolone acetonide (TA) could be achieved. Under the optimized conditions, the reproducibility of the retention time (n = 4) for most of the compounds was less than +/-0.8% with the exception of A, Ps, and T. The average number of theoretical plates was 18 800 plates/m. The results were compared with those achieved by the modified micellar EKC (MEKC). MEEKC showed obvious advantages over MEKC for the separation of highly hydrophobic substances. To further evaluate the system, we tested the MEEKC method by analyzing corticosteroids in a spiked urine sample.

  19. Chitosan nanoparticles for controlled delivery of brimonidine tartrate to the ocular membrane.

    Science.gov (United States)

    Singh, K H; Shinde, U A

    2011-08-01

    Various efforts have been made to improve the bioavailability and to prolong the residence time of eye drops. Drug loaded polymeric nanoparticles offer several favorable biological properties. Thus, brimonidine tartrate (BT) loaded chitosan (CS) nanoparticles were prepared by inducing the ionic gelation upon addition of sodium tripolyphosphate (TPP). Nanoparticles were characterized by TEM, SEM, particle size, polydispersity index (PI), DSC, IR, entrapment efficiency which gave an insight of physicochemical interaction that influenced the CS nanoparticle formation and entrapment of BT. In vitro release of BT nanoparticle showed sustained release over the period of 4 h in saline phosphate buffer pH 7.4. Both placebo and BT loaded nanoparticles had a mean particle size range of about 270-370 nm with PI less than 0.5. DSC studies demonstrated structural interactions between BT, TPP and CS matrix. Entrapment efficiency of the CS nanoparticles ranged from 36-49% depending on the CS:TPP weight ratio. In vivo studies confirmed a significant sustained effect of BT nanoparticles compared to conventional eye drops. These results suggest that BT loaded CS nanoparticles could help to reduce dosage frequency by sustained drug release in the treatment of glaucoma.

  20. Brimonidine tartrate poisoning in children: frequency, trends, and use of naloxone as an antidote.

    Science.gov (United States)

    Lai Becker, Melisa; Huntington, Noelle; Woolf, Alan D

    2009-02-01

    Brimonidine tartrate, a centrally acting selective alpha-2 adrenergic agonist with a toxicity that is often compared with that of clonidine, is used as eye drops to lower intraocular pressure in glaucoma. We investigated characteristics of childhood exposures to brimonidine-containing products. All brimonidine exposures in children 0 to 5 years of age between 1997 and 2005 were retrieved from the American Association of Poison Control Centers' Toxic Exposure Surveillance System database and the US Food and Drug Administration's Medwatch Adverse Events Reporting System. The design of the study was retrospective, and the main outcome measures were frequency of exposures over time, reason, symptoms/signs of toxicity, dose, management site, treatment, and outcome. There were 413 brimonidine reports in the Toxic Exposure Surveillance System and 340 in the Adverse Events Reporting System during the 9 years under study, of which 185 Toxic Exposure Surveillance System reports involved children brimonidine ingestions should be medically evaluated and monitored for an extended period. Indications for the use of naloxone in brimonidine poisoning remain uncertain.

  1. Effect of brimonidine tartrate 0.10% ophthalmic solution on pupil diameter.

    Science.gov (United States)

    Shemesh, Gabi; Moisseiev, Elad; Lazar, Moshe; Kesler, Anat

    2011-03-01

    To evaluate the effect of brimonidine tartrate 0.10% ophthalmic solution on pupil diameter under light and dark luminance conditions. Ophthalmology Department, Tel Aviv Medical Center, Tel Aviv, Israel. Case series. The pupil diameter was measured with a Colvard pupillometer in eyes of healthy volunteers under light (5.0 candelas [cd]/m(2)) and dark (0.0 cd/m(2)) luminance conditions before brimonidine 0.10% instillation and after 30 minutes, 3 hours, and 6 hours. The mean age of the 26 volunteers (52 eyes) was 34.73 years (range 19 to 60 years). Under light conditions, the mean pupil diameter was 4.98 mm ± 0.83 (SD) before instillation of brimonidine 0.10% and 4.64 ± 0.82 mm after instillation. The difference was not statistically significant, with 13.4% of eyes having a clinically significant reduction (>1.0 mm) in pupil diameter after 6 hours. Under dark conditions, the mean pupil diameter was 6.76 ± 1.08 mm before instillation of brimonidine 0.10% and 5.30 ± 0.85 mm after instillation; the difference was statistically significant (PBrimonidine 0.10% ophthalmic solution had an antimydriatic effect under dark luminance conditions and had a negligible effect on pupil diameter under light luminance conditions. The effect was similar to that reported in studies using higher concentrations of brimonidine. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  2. Nanovesicular formulation of brimonidine tartrate for the management of glaucoma: in vitro and in vivo evaluation.

    Science.gov (United States)

    Maiti, Sabyasachi; Paul, Sayon; Mondol, Ranjit; Ray, Somasree; Sa, Biswanath

    2011-06-01

    In this study, nanovesicles were developed for brimonidine tartrate by film hydration technique and dispersed in viscous carbopol solution for ocular delivery. Scanning electron microscopy revealed spherical shape of the vesicles. As high as 32.27% drug entrapment efficiency was achieved depending upon the surfactant/cholesterol molar ratio (7:4 to 7:8). The vesicles were in the size range of 298.0-587.9 nm. Release study showed a biphasic drug-release pattern for the lyophilized vesicular formulation in buffered saline solution, i.e., initial burst release followed by gradual release over the period of 8 h. On contrary, the isolated vesicles reduced the burst effect in 3 h by two to three times and the drug release was comparatively slower at the intermediate ratio in both cases. With variation in cholesterol content, the drug release followed either first order or Higuchi's kinetics. Physically the lyophilized vesicular formulations were more stable at refrigerated temperature. DSC and X-RD analyses indicated loss of drug crystallinity in the vesicles. FTIR spectroscopy did not reveal any interaction between drug and excipients. The lyophilized formulation showed better ocular hypotensive activity than marketed drops on albino rabbits and in vivo efficacy was sustained up to 7.5 h. Furthermore, the formulation was found to be non-irritant to the rabbit eye. Hence, the lyophilized vesicles, when dispersed in viscous carbopol solution, had the potential in reducing dosing frequency and could improve patient compliance.

  3. In vitro characterization of a controlled-release ocular insert for delivery of brimonidine tartrate.

    Science.gov (United States)

    Mealy, J E; Fedorchak, M V; Little, S R

    2014-01-01

    Glaucoma is the second leading cause of blindness in the US. Brimonidine tartrate (BT) is a modern anti-glaucoma agent that is currently administered as frequently as a thrice-daily topical eye drop medication. Accordingly, compliance with BT regimens is low, limiting overall effectiveness. One attempt that has previously proved effective in addressing non-adherence is the formation of ocular inserts, such as the Ocusert(®), whose diffusion-based control released an older drug (pilocarpine) for a week-long period. Modern controlled drug-release technology provides an avenue for extending the release of practically any drug (including new drugs such as BT) for as long as 1 month from a singular insert. Currently, no controlled-release formulations for BT exist. This work outlines the development and characterization of a BT-releasing ocular insert designed from poly(lactic co-glycolic) acid/polyethylene glycol (PEG). It was found that a formulation containing 15% PEG can be created that produces a linear BT-release profile corresponding to BT eye drop delivery estimates. Additionally, these inserts were shown, through the use of atomic force microscopy and scanning electron microscopy, to have smooth surfaces and physical properties suitable for ophthalmic use. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Sustained ocular delivery of brimonidine tartrate using ion activated in situ gelling system.

    Science.gov (United States)

    Geethalakshmi, A; Karki, Roopa; Jha, Sajal Kumar; Venkatesh, D P; Nikunj, B

    2012-03-01

    The poor bioavailability and therapeutic response exhibited by conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of an in situ gelling systems that are instilled as drops into the eye and undergo a sol-to-gel transition in the cul-de-sac which improves patient compliance as the dosage regimen is one drop of the dosage form twice a day. The loss of drug overcomes due to the immediate gel formation between the eye membrane and the drug being entrapped simultaneously in sol-gel transition in the cul de sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antiglaucomal agent, brimonidine tartrate based on the concept of ion-activated in situ gelation. Gelrite was used as the gelling agent, which gels in the presence of mono or divalent cations present in the lacrimal fluid. The formulations were evaluated for clarity, pH measurement, gelling capacity, drug content estimation, rheological study, in-vitro diffusion study, antibacterial activity, isotonicity testing, eye irritation testing. In the developed formulations Gelrite Brimonidine-3 (GB3) exhibited sustained release of drug from formulation over a period of 8 hrs thus increasing residence time of the drug, non-irritating with no ocular damage or abnormal clinical signs to the cornea, iris or conjunctiva, stable and sterile. These results demonstrate that the developed system is an alternative to conventional ophthalmic drops, with better patient compliance, and is industrially oriented and economical.

  5. Validated spectophotometric methods for the assay of cinitapride hydrogen tartrate in pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Satyanarayana K.V.V.

    2013-01-01

    Full Text Available Three simple, selective and rapid spectrophotometric methods have been established for the determination of cinitapride hydrogen tartrate (CHT in pharmaceutical tablets. The proposed methods are based on the diazotization of CHT with sodium nitrite and hydrochloric acid, followed by coupling with resorcinol, 1-benzoylacetone and 8-hydroxyquinoline in alkaline medium for methods A, B and C respectively. The formed azo dyes are measured at 442, 465 and 552 nm for methods A, B and C respectively. The parameters that affect the reaction were carefully optimized. Under optimum conditions, Beer’s law is obeyed over the ranges 2.0-32.0, 1.0-24.0 and 1.0-20.0 μg. mL-1 for methods A, B, and C, respectively. The calculated molar absorptivity values are 1.2853 x104, 1.9624 x104 and 3.92 x104 L.mol-1.cm-1 for methods A, B and C, respectively. The results of the proposed procedures were validated statistically according to ICH guidelines. The proposed methods were successfully applied to the determination of CHT in Cintapro tablets without interference from common excipients encountered.

  6. Tartrate-resistant acid phosphatase as a biomarker of bone turnover in dog

    Directory of Open Access Journals (Sweden)

    C.P Sousa

    2011-02-01

    Full Text Available Values of serum tartrate-resistant acid phosphatase ( TRAP activity were obtained in adult dogs and its biological variability was assessed. Nine healthy skeletally mature Portuguese Podengo dogs were used for the determination of TRAP, total and bone alkaline phosphatase serum activities, and also to study their relationship with serum minerals, namely calcium (Ca, phosphorous (P, and magnesium (Mg. The serum TRAP activity was 2.19±0.56IU/mL, with intra-individual variation of 18.3% and inter-individual variation of 25.6%. Significant correlations were observed between serum TRAP activity and Ca (r=-0.3431; P<0.05, Ca and Mg (r=-0.787; P<0.01, and TRAP and Mg (r=0.397; P<0.05. The results indicate that serum TRAP activity in dog could be of great value in research and in clinical practice, providing complementary non-invasive information on bone metabolism

  7. Development of a novel dry powder inhalation formulation for the delivery of rivastigmine hydrogen tartrate.

    Science.gov (United States)

    Simon, Alice; Amaro, Maria Inês; Cabral, Lucio Mendes; Healy, Anne Marie; de Sousa, Valeria Pereira

    2016-03-30

    The purpose of this study was to prepare engineered particles of rivastigmine hydrogen tartrate (RHT) and to characterize the physicochemical and aerodynamic properties, in comparison to a lactose carrier formulation (LCF). Microparticles were prepared from ethanol/water solutions containing RHT with and without the incorporation of L-leucine (Leu), using a spray dryer. Dry powder inhaler formulations prepared were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, ATR-FTIR, differential scanning calorimetry, bulk and tapped density, dynamic vapour sorption and in vitro aerosol deposition behaviour using a next generation impactor. The smooth-surfaced spherical morphology of the spray dried microparticles was altered by adding Leu, resulting in particles becoming increasingly wrinkled with increasing Leu. Powders presented low densities. The glass transition temperature was sufficiently high (>90 °C) to suggest good stability at room temperature. As Leu content increased, spray dried powders presented lower residual solvent content, lower particle size, higher fine particle fraction (FPFMMAD). The LCF showed a lower FPF and higher MMAD, relative to the spray dried formulations containing more than 10% Leu. Spray dried RHT powders presented better aerodynamic properties, constituting a potential drug delivery system for oral inhalation. Copyright © 2016. Published by Elsevier B.V.

  8. 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.

  9. 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.

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

    Science.gov (United States)

    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.

  11. 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....

  12. 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.

  13. 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

  14. Variations of cyclic alternating pattern rate and homeostasis of sleep organization: a controlled study on the effects of white noise and zolpidem.

    Science.gov (United States)

    Terzano, M G; Parrino, L; Fioriti, G; Farolfi, A; Spaggiari, M C; Anelli, S; Arcelloni, T

    1988-04-01

    The Cyclic Alternating Pattern (CAP) is a physiologic structure of normal non-REM (NREM) sleep, functionally correlated to long-lasting arousal instability. In 12 healthy volunteers, a continuous 45 dB (A) white noise induced no remarkable changes on the standard sleep parameters. However, compared to the baseline conditions, the acoustic perturbation determined a significant increase of the Cyclic Alternating Pattern Rate (CAPR), that measures the amount of CAP during sleep. Ten mg of zolpidem, a novel imidazopyridine hypnotic compound, did not modify the structure of unperturbed sleep, but induced a highly significant reduction of the increased values of CAP Rate due to white noise. The homeostatic function of CAP is stressed. CAPR appears to be a highly sensitive indicator of environmental modification during sleep.

  15. 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....

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. [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.

  7. 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.

  8. 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

  9. 28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres.

    Science.gov (United States)

    Fedorchak, Morgan V; Conner, Ian P; Medina, Carlos A; Wingard, Jeremy B; Schuman, Joel S; Little, Steven R

    2014-08-01

    Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 μg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Comparison of the neuroprotective effects of brimonidine tartrate and melatonin on retinal ganglion cells.

    Science.gov (United States)

    Marangoz, Deniz; Guzel, Elif; Eyuboglu, Signem; Gumusel, Asli; Seckin, Ismail; Ciftci, Ferda; Yilmaz, Bayram; Yalvac, Ilgaz

    2017-11-20

    We aimed to compare the neuroprotective effects of brimonidine tartrate (BRT) and melatonin (MEL) on retinal ganglion cells (RGCs) in a rat glaucoma model. Thirty-six adult Wistar albino rats were allocated into six groups: control (C), glaucoma (G), BRT, MEL, G + BRT and G + MEL. After establishing the glaucoma model, intraocular pressure (IOP) of all animals measured at day 4 and day 30 was compared statistically with day 0 and day 4, respectively. Prior to sacrification at day 30 for histological evaluation and TUNEL analysis, retrograde labeling of non-apoptotic RGCs with 3% Fluorogold was performed and RGCs were evaluated under fluorescein microscope. IOP measurements at day 4 were significantly higher than basal measurements in all glaucoma groups. BRT alone induced a time-dependent decrease in IOP (p < 0.05), while MEL alone failed to reduce IOP. However, both BRT and MEL reduced IOP in the presence of glaucoma at day 30 (p < 0.05). BRT treatment significantly reversed the reduced non-apoptotic RGC counts (p < 0.01) and increased TUNEL-positive RGCs (p < 0.001) to control group levels in the presence of glaucoma. However, no statistical significance was found between groups G and G + MEL considering 3% Fluorogold-labeled cell counts and apoptotic index values. Our study revealed that systemic administration of BRT also has an IOP reducing effect. MEL has no neuroprotective effect on RGCs; on the other hand, BRT acts as a neuroprotective agent against glaucomatous injury, when applied systemically.

  11. Brimonidine tartrate-eudragit long-acting nanoparticles: formulation, optimization, in vitro and in vivo evaluation.

    Science.gov (United States)

    Bhagav, Prakash; Upadhyay, Hariom; Chandran, Sajeev

    2011-12-01

    In the present study, an effort was made to design prolonged release Eudragit nanoparticles of brimonidine tartrate by double emulsion-solvent evaporation technique for the treatment of open-angle glaucoma. The effect of various formulation variables like initial drug amount, lecithin proportion, phase volume and pH, secondary emulsifier and polymer proportion were studied. Various process variables like energy and duration of emulsification, lyophilization on the characteristics of nanoparticles and in vitro drug release profile were studied. The selected formulations were subjected to in vivo intraocular pressure-lowering efficacy studies by administering aqueous dispersion of nanoparticles into the lower cul de sac of glaucomatous rabbits. The prepared Eudragit-based nanoparticles were found to have narrow particle size range and improved drug loading. The investigated process and formulation variables found to have significant effect on the particle size, drug loading and entrapment efficiency, and in vitro drug release profile of nanoparticles. The selected formulations upon in vivo ocular irritability and tolerability tests were found to be well tolerated with no signs of irritation. In vivo pharmacodynamic efficacy studies revealed that the selected nanoparticle formulations significantly improved the therapy as area under the ∆IOP vs. time curve [AUC((∆IOP vs. t))] showed several fold increase in intensity and duration of intraocular pressure (IOP) decrease. All the selected nanoparticle formulations were found to prolong the drug release in vitro and prolong IOP reduction efficacy in vivo, thus rendering them as a potential carrier in developing improved drug delivery systems for the treatment of glaucoma.

  12. Comparison of metoprolol tartrate multiple-unit lipid matrix systems produced by different technologies.

    Science.gov (United States)

    Aleksovski, Aleksandar; Van Bockstal, Pieter-Jan; Roškar, Robert; Sovány, Tamás; Regdon, Géza; De Beer, Thomas; Vervaet, Chris; Dreu, Rok

    2016-06-10

    The aim of this study was to develop, evaluate and compare extended release mini-matrices based on metoprolol tartrate (MPT) and either glyceryl behenate (GB) or glyceryl palmitostearate (GPS). Mini-matrices were produced by three different techniques: hot melt extrusion, compression of melt granulates and prilling. Hot-melt extrusion and compression of granules obtained from melted material proved to be reliable, robust and reproducible techniques with aim of obtaining extended release matrices. Prilling tended to be susceptible to increased melt viscosity. Direct compression was not applicable for mini-matrix production due to poor powder flow. In general MPT release from all matrices was affected by its loading and the size of the units/particles. Processing of GB-MPT mixtures by different techniques did not lead to different drug release rates and patterns, while in case of GPS differently obtained matrices provided diverse MPT release outcomes. Matrices based on GB tended to have higher porosity compared to ones composed of GPS and thus most of the GB-based formulations showed faster drug delivery. FT-IR analysis revealed no interactions between primary components used for matrix production and Raman mapping outlined uniform MPT distribution throughout the units. DSC and X-ray studies revealed significant changes in the crystallinity of glycerides after storage under room conditions (GPS samples) and at increased temperature (GB and GPS samples), which was correlated to the changes seen in drug release rate and pattern after storage. Media composition in general tended to insignificantly affect GB matrices, while in case of GPS matrices increasing the pH and presence of biorelevant compounds induced faster drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Titrimetric and Spectrophotometric Determination of Metaprolol tartrate in Pharmaceuticals Using N-Bromosuccinimide

    Directory of Open Access Journals (Sweden)

    K. Basavaiah

    2007-01-01

    Full Text Available One titrimetric and two spectrophotometric methods are presented for the assay of metaprolol tartrate (MPT in bulk drug and in tablets. The methods employ N-bromosuccinimide (NBS as the oxidimetric reagent and two dyes, methyl orange and indigo carmine as spectrophotometric reagents. In titrimetry, an acidified solution of MPT is treated with a known excess amount of NBS and after a definite time, the unreacted oxidant is determined by iodometric back titration. Spectrophotometry involves adding a measured excess of NBS to MPT in acid medium followed by determination of residual NBS by reacting with a fixed amount of either methyl orange and measuring the absorbance at 520 nm (Method A or indigo carmine and measuring the absorbance at 610 nm (Method B. In all the methods, the amount of NBS reacted corresponds to the amount of MPT. Reaction conditions have been optimized. Titrimetry allows the determination of 1 - 12 mg of MPT and the calculations are based on a 1: 4 (MPT: NBS reaction stoichiometry. In spectrophotometry, the measured absorbance is found to increase linearly with the concentration of MPT serving as basis for quantitation. The systems obey Beer’s law for 0.5 - 4.0 μg mL-1 and 1.25 - 10.0 μg mL-1 for method A and method B, respectively. The apparent absorptivities are calculated to 1.07 × 105 be and 4.22 × 104 L mol cm-1 for method A and method B, respectively. The methods developed were applied to the assay of MPT in commercial tablet formulations, and the results were compared statistically with those of a reference method. The accuracy and reliability of the methods were further ascertained by performing recovery tests via standard-addition method.

  14. 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 ...

  15. Formulation and evaluation of stimuli-sensitive hydrogels of timolol maleate and brimonidine tartrate for the treatment of glaucoma.

    Science.gov (United States)

    Dubey, Akhilesh; Prabhu, Prabhakara

    2014-07-01

    Stimuli-sensitive hydrogels are hydrophilic, three-dimensional, polymeric network structure capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature, and ionic change. Owing to the drawback of conventional therapy for ocular delivery, and to provide additive effect on intraocular pressure (IOP) reduction, stimuli sensitive hydrogel membranes containing a combination of timolol maleate and brimonidine tartrate were formulated for the treatment of glaucoma. Stimuli-sensitive hydrogel were formulated by timolol maleate and brimonidine tartrate. Poly acrylic acid (carbopol C 934p) is used as a gelling agent, hydroxylpropyl methylcellulose as viscolizer, sodium chloride as tonicity agent. Bezalkonium chloride as preservative. White rabbits of both sexes, weighing between 2 and 3 kg were used for the study. Stirring of ingredients in pH 4 phosphate buffers at high speed was carried out. Viscosity of the prepared hydrogels lies in the optimum range that is, 25-55 cps. Infrared spectroscopy studies show that there is no interaction between the drug and polymer. Drug released up to 90% at the end of 8 h. The hydrogel membranes were found to be sterile, nonirritant to the eye. Marketed formulation showed a decrease in IOP up to 14 mmHg at the end of 5 h and then elimination of drug, F2 and F6 maintain the sustained effect up to 12 h. Stimuli-sensitive hydrogels was successfully formulated and evaluated for rheological studies, drug release studies, drug interaction studies, sterility studies, ocular irritation studies, and in vivo studies. IOP lowering activity of the combination of timolol maleate and brimonidine tartrate in stimuli-sensitive hydrogel was better when compared with alone medication, which shows the additive effect of combination medication.

  16. Vitreous and aqueous concentrations of brimonidine following topical application of brimonidine tartrate 0.1% ophthalmic solution in humans.

    Science.gov (United States)

    Takamura, Yoshihiro; Tomomatsu, Takeshi; Matsumura, Takehiro; Takihara, Yuji; Kozai, Seiko; Arimura, Shogo; Yokota, Satoshi; Inatani, Masaru

    2015-06-01

    To determine the vitreous and aqueous concentrations of brimonidine after topical application of the ophthalmic solution 0.1%. The prospective observational case series included patients with an idiopathic epiretinal membrane or macular hole who were scheduled for a pars plana vitrectomy. Brimonidine tartrate ophthalmic solution 0.1% was topically administered twice daily for 1 week preoperatively. Vitreous and aqueous humor was collected before vitrectomy, and then, the brimonidine concentration was measured with liquid chromatography tandem spectrometry (LC/MS/MS). Twenty-four patients (19 phakic eyes and 5 pseudophakic eyes) were enrolled. The mean concentrations in the aqueous humor and vitreous were 336.0 ± 276.2 and 4.8 ± 3.2 nM, respectively. A significant relationship was observed between the vitreous and aqueous samples (P = 0.034, R(2) = 0.22). Nineteen (79%) of the 24 eyes showed more than 2 nM of brimonidine tartrate concentration in the vitreous. In the phakic eyes, the mean concentration of brimonidine in the vitreous was 4.9 ± 3.3 nM, while the mean concentration in the pseudophakic eyes was 4.1 ± 2.4 nM, demonstrating no significant difference between pseudophakic and phakic eyes (P = 0.59). After 1 week of dosing, in most of the patients who topically received brimonidine tartrate 0.1%, the concentration in the vitreous of the molecule was above 2 nM, which is known to activate neuroprotective α-2 receptors in animal retina. The drug penetration into the vitreous seems to be independent of lens status.

  17. The vacuolar channel VvALMT9 mediates malate and tartrate accumulation in berries of Vitis vinifera.

    Science.gov (United States)

    De Angeli, Alexis; Baetz, Ulrike; Francisco, Rita; Zhang, Jingbo; Chaves, Maria Manuela; Regalado, Ana

    2013-08-01

    Vitis vinifera L. represents an economically important fruit species. Grape and wine flavour is made from a complex set of compounds. The acidity of berries is a major parameter in determining grape berry quality for wine making and fruit consumption. Despite the importance of malic and tartaric acid (TA) storage and transport for grape berry acidity, no vacuolar transporter for malate or tartrate has been identified so far. Some members of the aluminium-activated malate transporter (ALMT) anion channel family from Arabidopsis thaliana have been shown to be involved in mediating malate fluxes across the tonoplast. Therefore, we hypothesised that a homologue of these channels could have a similar role in V. vinifera grape berries. We identified homologues of the Arabidopsis vacuolar anion channel AtALMT9 through a TBLASTX search on the V. vinifera genome database. We cloned the closest homologue of AtALMT9 from grape berry cDNA and designated it VvALMT9. The expression profile revealed that VvALMT9 is constitutively expressed in berry mesocarp tissue and that its transcription level increases during fruit maturation. Moreover, we found that VvALMT9 is targeted to the vacuolar membrane. Using patch-clamp analysis, we could show that, besides malate, VvALMT9 mediates tartrate currents which are higher than in its Arabidopsis homologue. In summary, in the present study we provide evidence that VvALMT9 is a vacuolar malate channel expressed in grape berries. Interestingly, in V. vinifera, a tartrate-producing plant, the permeability of the channel is apparently adjusted to TA.

  18. Bis(di-2-pyridylmethanediol-κ3N,O,N′copper(II dl-tartrate

    Directory of Open Access Journals (Sweden)

    Li Guo

    2008-12-01

    Full Text Available The reaction of di-2-pyridyl ketone with copper dichloride dihydrate and tartaric acid in water afforded the title compound, [Cu(C11H10N2O22]C4H4O6. The CuII atom lies on an inversion center N,O,N′-chelated by two di-2-pyridylmethanediol ligands in a tetragonally distorted octahedral geometry. The tartrate anion is also located on an inversion center and has disordered hydroxyl groups, each with an occupancy factor of 0.5. The hydroxyl groups of the complex cation are hydrogen bonded to the carboxylate groups of the anion, thus connecting the two building units.

  19. Fluorescence-based staining for tartrate-resistant acidic phosphatase (TRAP) in osteoclasts combined with other fluorescent dyes and protocols.

    Science.gov (United States)

    Filgueira, Luis

    2004-03-01

    Osteoclasts are the only bone-resorbing cells. In addition to other specific properties, osteoclasts are characterized by their expression of tartrate-resistant acidic phosphatase (TRAP), which is usually detected using a histochemical method for light microscopy. Using ELF97 phosphatase substrate, this study describes a new fluorescence-based method for TRAP detection. The fluorescence-based ELF97 TRAP stain not only results in a better resolution of the TRAP-positive granules, because confocal microscopy can be applied for image acquisition and analysis, but it reveals additional and more specific information about osteoclasts because it can be combined with other fluorescence-based methods.

  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. 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...

  2. 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....

  3. 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.

  4. 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.

  5. 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...

  6. Study of complex equilibria in niobium(V) and vanadium(V) systems with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol, tartrate and hydrogen peroxide using RP-HPLC

    Energy Technology Data Exchange (ETDEWEB)

    Oszwaldowski, S.; Jarosz, M. [Politechnika Warszawska, Warsaw (Poland)

    1997-12-01

    Complex equilibria in multiligand niobium(V) systems with 2-(5-bromo-2-pyridilazo)-5-diethyl aminophenol (5-Br-PADAP), tartrate and hydrogen peroxide and vanadium(V) with 5-Br-PADP and tartrate were evaluated by reversed-phase high-performance liquid chromatography (RP-HPLC) using C{sub 18} column and VIS detection at 590 nm. In Nb(V)-H{sub 2}O{sub 2}-tartrate-(5-Br{sub P}ADAP) system formation of multiligand niobium complex, non-reactive towards 5-Br-PADAP, was postulated. For V(V) system distribution of metal ion between V(V)-(5-Br-PADAP) binary and V(V)-tartrate-(5-Br-PADAP) ternary complexes were evaluated. On this base it was proved, that coloured ternary vanadium complex is only an intermediate stage in the formation of stable V(V)-tartrate binary complex. (author). 14 refs, 7 figs.

  7. 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.

  8. 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.

  9. 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.

  10. Optimization of the tartrate-resistant acid phosphatase detection by histochemical method

    Directory of Open Access Journals (Sweden)

    M. J. Galvão

    2011-02-01

    Full Text Available According to the new KDIGO (Kidney Disease Improving Global Outcomes guidelines, the term of renal osteodystrophy, should be used exclusively in reference to the invasive diagnosis of bone abnormalities. Due to the low sensitivity and specificity of biochemical serum markers of bone remodelling,the performance of bone biopsies is highly stimulated in dialysis patients and after kidney transplantation. The tartrate-resistant acid phosphatase (TRACP is an iso-enzyme of the group of acid phosphatases, which is highly expressed by activated osteoclasts and macrophages. TRACP in osteoclasts is in intracytoplasmic vesicles that transport the products of bone matrix degradation. Being present in activated osteoclasts, the identification of this enzyme by histochemistry in undecalcified bone biopsies is an excellent method to quantify the resorption of bone. Since it is an enzymatic histochemical method for a thermolabile enzyme, the temperature at which it is performed is particularly relevant. This study aimed to determine the optimal temperature for identification of TRACP in activated osteoclasts in undecalcified bone biopsies embedded in methylmethacrylate. We selected 10 cases of undecalcified bone biopsies from hemodialysis patients with the diagnosis of secondary hyperparathyroidism. Sections of 5 μm were stained to identify TRACP at different incubation temperatures (37º, 45º, 60º, 70º and 80ºC for 30 minutes. Activated osteoclasts stained red and trabecular bone (mineralized bone was contrasted with toluidine blue. This approach also increased the visibility of the trabecular bone resorption areas (Howship lacunae. Unlike what is suggested in the literature and in several international protocols, we found that the best results were obtained with temperatures between 60ºC and 70ºC. For technical reasons and according to the results of the present study, we recommended that, for an incubation time of 30 minutes, the reaction should be

  11. Optimization of the tartrate-resistant acid phosphatase detection by histochemical method

    Science.gov (United States)

    Galvão, M.J.; Santos, A. R.; Ribeiro, M.D.; Ferreira, A.; Nolasco, F.

    2011-01-01

    According to the new kidney disease improving global outcomes (KDIGO) guidelines, the term of renal osteodystrophy, should be used exclusively in reference to the invasive diagnosis of bone abnormalities. Due to the low sensitivity and specificity of biochemical serum markers of bone remodelling, the performance of bone biopsies is highly stimulated in dialysis patients and after kidney transplantation. The tartrate-resistant acid phosphatase (TRACP) is an iso-enzyme of the group of acid phosphatases, which is highly expressed by activated osteoclasts and macrophages. TRACP in osteoclasts is in intracytoplasmic vesicles that transport the products of bone matrix degradation. Being present in activated osteoclasts, the identification of this enzyme by histochemistry in undecalcified bone biopsies is an excellent method to quantify the resorption of bone. Since it is an enzymatic histochemical method for a thermolabile enzyme, the temperature at which it is performed is particularly relevant. This study aimed to determine the optimal temperature for identification of TRACP in activated osteoclasts in undecalcified bone biopsies embedded in methylmethacrylate. We selected 10 cases of undecalcified bone biopsies from hemodialysis patients with the diagnosis of secondary hyperparathyroidism. Sections of 5 µm were stained to identify TRACP at different incubation temperatures (37°, 45°, 60°, 70° and 80°C) for 30 minutes. Activated osteoclasts stained red and trabecular bone (mineralized bone) was contrasted with toluidine blue. This approach also increased the visibility of the trabecular bone resorption areas (Howship lacunae). Unlike what is suggested in the literature and in several international protocols, we found that the best results were obtained with temperatures between 60°C and 70°C. For technical reasons and according to the results of the present study, we recommended that, for an incubation time of 30 min, the reaction should be carried out at 60

  12. 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

  13. 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

  14. Improved insomnia symptoms and sleep-related next-day functioning in patients with comorbid major depressive disorder and insomnia following concomitant zolpidem extended-release 12.5 mg and escitalopram treatment: a randomized controlled trial.

    Science.gov (United States)

    Fava, Maurizio; Asnis, Gregory M; Shrivastava, Ram K; Lydiard, Bruce; Bastani, Bijan; Sheehan, David V; Roth, Thomas

    2011-07-01

    This investigation was performed to assess the efficacy and safety of zolpidem extended-release in patients with insomnia associated with major depressive disorder (MDD). Patients (N = 385) received open-label escitalopram 10 mg/d and were randomized to concomitant zolpidem extended-release 12.5 mg/night or placebo for 8 weeks (phase 1) in a randomized, parallel-group, multicenter trial. Responders (≥ 50% in 17-item Hamilton Depression Rating Scale [HDRS(17)] score) continued 16 weeks of double-blind treatment (phase 2); escitalopram only was given during a 2-week run-out period. The study was conducted between February 2006 and June 2007. The primary efficacy measure was change from baseline in subjective total sleep time. Secondary efficacy measures included subjective sleep-onset latency, number of awakenings, wake time after sleep onset, sleep quality, sleep-related next-day functioning, HDRS(17), Sleep Impact Scale score, Patient and Clinical Global Impressions of Insomnia Treatment, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, and the Quality of Life Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study; sleep measures were also evaluated during the run-out period. Throughout phase 1, zolpidem extended-release led to significantly greater improvements in total sleep time (P sleep onset, sleep onset latency, number of awakenings, and sleep quality (P ≤ .0003), and some measures of sleep-related next-day functioning but not in depressive symptoms or quality of life. During phase 2, improvements with the zolpidem extended-release/escitalopram group occurred for total sleep time (significant [P depressive symptoms or quality of life. The most common adverse events associated with combination treatment included nausea, somnolence, dry mouth, dizziness, fatigue, and amnesia. Zolpidem extended-release administered concomitantly with escitalopram for up to 24 weeks was well tolerated

  15. Synthesis of a Parkinson's Disease Treatment Drug, the "R,R"-Tartrate Salt "of R"-Rasagiline: A Three Week Introductory Organic Chemistry Lab Sequence

    Science.gov (United States)

    Aguilar, Noberto; Garcia, Billy; Cunningham, Mark; David, Samuel

    2016-01-01

    A synthesis of the "R,R"-tartrate salt of the popular anti-Parkinson's drug "R"-rasagiline (Azilect) was adapted to introduce the organic laboratory student to a medically relevant synthesis. It makes use of concepts found in the undergraduate organic chemistry curriculum, appropriately fits into three approximately 4 h lab…

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. [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.

  5. 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.

  6. Ekspresi Tartrate-Resistant Acid Phosphatase-5b pada Epifisis Tulang Femur Tikus Ovariektomi yang Mengkonsumsi Calcitriol dan Raloxifene (TARTRATE-RESISTANT ACID PHOSPHATASE-5b EXPRESSION OF EPIPHYSYS DISTALIS FEMUR OVARIECTOMIZED RATS CONSUMING CALCITRIO

    Directory of Open Access Journals (Sweden)

    Hartiningsih .

    2016-03-01

    Full Text Available Tartrate resistant alkaline phosphatase 5b (TRACP5b is secreted by osteoclasts during bonedifferentiation and resorption. The objective of the research was to study TRAP5b expression inovariectomized Wistar rat consuming the combinations of calcitriol and raloxifene supplementation foreight weeks. Twenty five female Wistar rats aged eight weeks were randomly divided into five groups:normal control (NK, ovariectomy control (OVK, ovariectomy+calcitriol supplementation (OVD,ovariectomy+ raloxifene supplementation (OVR, and ovariectomy+calcitriol+ raloxifene supplementation(OVDR. At the end of the treatment, blood samples were taken from plexus orbitalis medialis forestrogen analysis. All rats were euthanized, the uteri were taken and weighed. Left femur was taken forhistopatological examination and immunohistochemistry TRAP5b using monoclonal antibody anti TRAP5bwhich was detected with streptavidin-biotin. The results showed that estrogen levels of the rats in OVKgroup were significantly decreased compared to the rats in NK group, meanwhile estrogen levels in the OVDR rat group were significantly decreased compared to the NK and OVK rat group. Histopathologicalobservation of distal femur epiphysis in group NK showed normal structure, meanwhile, distal femurepiphysis in OVK group was found osteoporosis, with some abnormalities, such as: increased of bonemarrow space, domination of adipocytes in the bone marrow, and decrease of trabecular bone speculum inepiphysis. Histopathological findings of distal femur epiphysis in OVDR group were increased of trabecularbone speculum in epiphysis and the domination of adipocytes in the bone marrow of epiphysis.Immunohistochemistry of distal femur epiphysis in OVDR group revealed increasing tartrate resistantalkaline phosphatase 5b (TRAP5b expression in trabecular bone, which was located in bone marrow spaceand trabecular speculum surface as well. It can be concluded that the combination of calcitriol and

  7. Enantioseparation of Racemic Flurbiprofen by Aqueous Two-Phase Extraction With Binary Chiral Selectors of L-dioctyl Tartrate and L-tryptophan.

    Science.gov (United States)

    Chen, Zhi; Zhang, Wei; Wang, Liping; Fan, Huajun; Wan, Qiang; Wu, Xuehao; Tang, Xunyou; Tang, James Z

    2015-09-01

    A novel method for chiral separation of flurbiprofen enantiomers was developed using aqueous two-phase extraction (ATPE) coupled with biphasic recognition chiral extraction (BRCE). An aqueous two-phase system (ATPS) was used as an extracting solvent which was composed of ethanol (35.0% w/w) and ammonium sulfate (18.0% w/w). The chiral selectors in ATPS for BRCE consideration were L-dioctyl tartrate and L-tryptophan, which were screened from amino acids, β-cyclodextrin derivatives, and L-tartrate esters. Factors such as the amounts of L-dioctyl tartrate and L-tryptophan, pH, flurbiprofen concentration, and the operation temperature were investigated in terms of chiral separation of flurbiprofen enantiomers. The optimum conditions were as follows: L-dioctyl tartrate, 80 mg; L-tryptophan, 40 mg; pH, 4.0; flurbiprofen concentration, 0.10 mmol/L; and temperature, 25 °C. The maximum separation factor α for flurbiprofen enantiomers could reach 2.34. The mechanism of chiral separation of flurbiprofen enantiomers is discussed and studied. The results showed that synergistic extraction has been established by L-dioctyl tartrate and L-tryptophan, which enantioselectively recognized R- and S-enantiomers in top and bottom phases, respectively. Compared to conventional liquid-liquid extraction, ATPE coupled with BRCE possessed higher separation efficiency and enantioselectivity without the use of any other organic solvents. The proposed method is a potential and powerful alternative to conventional extraction for separation of various enantiomers. © 2015 Wiley Periodicals, Inc.

  8. 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.

  9. [Effect of topical 0.1% brimonidine tartrate and 0.5% timolol maleate on pulmonary and cardiovascular functions].

    Science.gov (United States)

    Araie, Makoto; Adachi, Mitsuru

    2012-07-01

    To compare the effects of topical 0.1% brimonidine tartrate and 0.5% timolol maleate on pulmonary and cardiovascular function. A single-masked, randomized, parallel, 4-week-long study. One hundred elderly volunteers without respiratory or cardiovascular diseases underwent a pulmonary function test, blood pressure and pulse measurements, and 12-lead electrocardiography. The patients were divided into 2 groups, the Brimonidine group and the Timolol group. The one-second forced expiratory volume (FEV1.0), generally used for respiratory function, showed a significantly greater reduction in the Timolol group. The decrease in systolic blood pressure in the Timolol group was significantly smaller than in the Brimonidine group. The decrease in pulse rate in the Brimonidine group was significantly smaller than in the Timolol group. There were no appreciable findings or abnormal changes in the 12-lead electrocardiograms in either group. Brimonidine is an antiglaucoma agent with lower pulmonary risk than timolol.

  10. Long-Term Subconjunctival Delivery of Brimonidine Tartrate for Glaucoma Treatment Using a Microspheres/Carrier System.

    Science.gov (United States)

    Pek, Y Shona; Wu, Hong; Mohamed, Siti Thaharah; Ying, Jackie Y

    2016-11-01

    Core-shell polymer microspheres with poly(d,l-lactic-co-glycolic acid) core and poly(l-lactic acid) (PLLA) shell are developed for the long-term subconjunctival release of brimonidine tartrate (BT) in order to reduce intraocular pressure (IOP) in the treatment of glaucoma. The PLLA-rich shell acts as a diffusion barrier, enabling linear release of BT over an extended period of 40 d. The microspheres are encased in a porous non-degradable methacrylate-based carrier for ease of subconjunctival implantation in a glaucoma-induced rabbit model. In vivo release of BT from the microspheres/carrier system has enabled a significant, immediate IOP reduction of 20 mmHg, which is sustained for 55 d. Long-term IOP reduction may be maintained by periodic replacement of the microspheres/carrier system. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Investigation on Growth, Structural, Spectral, Optical, and Mechanical Properties of an Organic Nonlinear Optical Material: Morpholinium Hydrogen Tartrate

    Directory of Open Access Journals (Sweden)

    R. Renugadevi

    2014-01-01

    Full Text Available Organic nonlinear optical crystal morpholinium hydrogen tartrate (MHT, with molecular formula [C8H15NO7], has been grown by slow evaporation solution technique. Single crystal X-ray diffraction study confirms that MHT crystallizes in orthorhombic system with noncentrosymmetric space group P212121. FTIR spectrum was recorded to identify the various functional groups of MHT. The various kinds of protons and carbons of MHT have been identified using 1H and 13C NMR spectral analyses. The range of optical absorption was ascertained by recording UV-Vis-NIR spectral studies. The TG/DTA studies revealed that the grown crystal is thermally stable up to 159.26°C. The mechanical property of the grown crystal was studied using Vickers microhardness studies. The relative second harmonic generation efficiency of MHT was determined using Kurtz and Perry powder technique; it was observed to be greater than that of KDP crystal.

  12. A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

    DEFF Research Database (Denmark)

    Cao, Qing-Ri; Choi, Jae-Seung; Liu, Yan

    2013-01-01

    Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation. Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling...... agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol(®) SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers. Results: The amount of HPMC, the grade of HPMC and the combination ratio...... of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f(2) > 50). Furthermore, the dissolution method and rotation speed showed no effects...

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

    Full Text Available Khaled Mohamed Hosny,1,2 Hisham Ahmed Mosli,3 Ali Habiballah Hassan4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 3Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Sildenafil citrate (SC, a drug used to treat erectile dysfunction, is available in tablet form but has three major problems. First, the drug displays inadequate aqueous solubility, which delays the onset of its action. Second, the drug undergoes extensive first-pass metabolism, resulting in a low (40% bioavailability. Third, the gastrointestinal effects of SC include dyspepsia and a burning sensation. The aim of this research was to prepare SC as a sublingual tablet utilizing soy polysaccharide as novel superdisintegrant to mitigate the abovementioned problems. The solubility of SC in various hydrophilic carrier solutions was estimated in order to prepare the drug as a coprecipitate. Sublingual tablets were prepared and evaluated for hardness, friability, drug content, wetting time, water absorption ratio, in vitro dispersion time, dissolution rate, and stability study. The pharmacokinetic study of the tablets was carried out on healthy volunteers. The results indicated that the co-precipitation of SC with polyvinylpyrollidone K30 enhanced the solubility of SC by more than eight folds. The tablet contained 8% soy polysaccharide as a superdisintegrant and provided a wetting time of 25 seconds, and in vitro dispersion times of 55 seconds. The drug release was found to be 95.6%. The prepared SC sublingual tablet also exhibited a rapid onset of action, and its bioavailability was enhanced 1.68-fold compared with that of the marketed tablets. It

  19. 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

  20. 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

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

    Science.gov (United States)

    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

  2. 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....

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Validation of a simultaneous analytical method for the detection of 27 benzodiazepines and metabolites and zolpidem in hair using LC-MS/MS and its application to human and rat hair.

    Science.gov (United States)

    Kim, Jihyun; Lee, Sooyeun; In, Sanghwan; Choi, Hwakyung; Chung, Heesun

    2011-04-15

    Benzodiazepines and zolpidem are controlled in many countries due to their inherent adverse effects of a high degree of tolerance and dependence. Recently, as some of these drugs have become distributed illegally and available through media such as the Internet, their abuse is becoming a serious social problem. Hair is a useful specimen to prove chronic drug use. In the present study, a simultaneous analytical method for the detection of 27 benzodiazepines and metabolites and zolpidem in hair was established and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The drugs and their metabolites in hair were extracted using methanol, filtered and injected on the LC-MS/MS. The following validation parameters of the method were satisfactory: selectivity, linearity, matrix effect, recovery, process efficiency, intra- and inter-assay precision and accuracy and processed sample stability. The limit of detection (LOD) and the limit of quantification (LOQ) were the total drug detected from the sample. The LODs ranged from 0.005 ng (zolpidem) to 0.5 ng (bromazepam and chlordiazepoxide) and the LOQs were 0.25 ng in every analyte except for bromazepam and chlordiazepoxide, for which they were 0.5 ng. The developed method was successfully applied to five legal cases involving use of benzodiazepines and zolpidem and to an animal study on drug incorporation into hair. Diazepam and its three metabolites, as well as lorazepam, were detected in hair from both the multiple- and single-dose administration groups of lean Zucker rats. The concentration of diazepam was higher than those of its metabolites in both dark grey and white hair from the multiple-dose administration groups, with the mean concentration ranges from 0.16 to 0.51 ng/mg and from 0.10 to 0.24 ng/mg, respectively. The mean concentration ranges of lorazepam were from 0.05 to 0.37 ng/mg in dark grey hair and from 0.11 to 0.45 ng/mg in white hair from the multiple-dose administration groups. Hair

  10. 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

  11. 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

  12. Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle-controlled pivotal studies.

    Science.gov (United States)

    Fowler, Joseph; Jackson, Mark; Moore, Angela; Jarratt, Michael; Jones, Terry; Meadows, Kappa; Steinhoff, Martin; Rudisill, Diane; Leoni, Matthew

    2013-06-01

    Brimonidine tartrate, a highly selective α2-adrenergic receptor agonist with potent vasoconstrictive activity, was shown to reduce erythema of rosacea. To assess the efficacy and safety of topical brimonidine tartrate gel 0.5% for the treatment of erythema of rosacea. Both studies were randomized, double-blind, and vehicle-controlled, with identical design. Subjects with moderate to severe erythema of rosacea were randomized 1:1 to apply topical brimonidine tartrate gel 0.5% or vehicle gel once-daily for 4 weeks, followed by a 4-week follow-up phase. Evaluations included severity of erythema based on Clinician's Erythema Assessment and Patient's Self-Assessment, as well as adverse events. Topical brimonidine tartrate gel 0.5% was significantly more efficacious than vehicle gel throughout 12 hours on days 1, 15, and 29, with significant difference observed as early as 30 minutes after the first application on day 1 (all Pbrimonidine tartrate gel 0.5% than for vehicle; however, most of the adverse events were dermatological, mild, and transient in nature. These data generated in controlled trials may be different from those in clinical practice. Once-daily brimonidine tartrate gel 0.5% has a good safety profile and provides significantly greater efficacy relative to vehicle gel for the treatment of moderate to severe erythema of rosacea, as early as 30 minutes after application.

  13. 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.

  14. 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

  15. 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

    Directory of Open Access Journals (Sweden)

    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.

  16. Efeitos do tartarato de metoprolol em pacientes portadores de insuficiência cardíaca Effects of metoprolol tartrate therapy in patients with heart failure

    Directory of Open Access Journals (Sweden)

    José Albuquerque de Figueiredo Neto

    2006-09-01

    Full Text Available OBJETIVO: Estudar os efeitos do tartarato de metoprolol em pacientes portadores de insuficiência cardíaca. MÉTODOS: Foram avaliados em estudo prospectivo, 50 pacientes (36 homens com insuficiência cardíaca, classe funcional II a IV, com 52±14,8 anos, e fração de ejeção do ventrículo esquerdo (FEVE 0,05. A freqüência cardíaca apresentou redução de 78,84±batimentos por minuto para 67,48±1,86 batimentos por minuto (pOBJECTIVE: To study the effects of metoprolol tartrate therapy in patients with heart failure. METHODS: Fifty patients (36 males aged 52±14.8 yrs, with functional class II to IV heart failure (HF and left ventricular ejection fraction (LVFE 0.05. Cardiac frequency decreased from 78.84±1.68 to 67.48±1.86 b.p.m. (p<0.001. CONCLUSION: The adding of metoprolol tartrate to the usual heart failure therapy is followed by an increase of ejection fraction, functional class improvement, and decrease of ventricular diameters and cardiac frequency. These results suggest anti-remodeling effects in patients with HF who utilize metoprolol tartrate in addition to the usual therapy.

  17. Improving downstream processes to recover tartaric acid, tartrate and nutrients from vinasses and formulation of inexpensive fermentative broths for xylitol production.

    Science.gov (United States)

    Salgado, José Manuel; Rodríguez, Noelia; Cortés, Sandra; Domínguez, José Manuel

    2010-10-01

    Vinasses, the main liquid wastes from the distillation process of grape marc and wine lees, are acidic effluents with high organic content, including acids, carbohydrates, phenols, and unsaturated compounds with high chemical oxygen demand, biological oxygen demand and solid concentrations. These wastes can be revalued to provide additional benefits when they are employed as feedstock of some compounds including tartaric acid, calcium tartrate and economic nutrients for the elaboration of fermentable broths. This study attempts to recover tartaric acid and calcium tartrate from vinasses. All the tartaric acid initially solubilised was recovered in both processes. The residual streams can be successfully employed as economic nutrients for the xylose to xylitol bioconversion, achieving higher global volumetric productivities (Q(P, xylitol) = 0.232 g L(-1) h(-1)) and products yields (Y(xylitol/S) = 0.57 g g(-1)) than fermentations carried out using commercial nutrients (Q(P, xylitol) = 0.193 g L(-1) h(-1) and Y(xylitol/S) = 0.55 g g(-1) respectively). Tartaric acid can be recovered from vinasses in the form of tartaric acid crystals and calcium tartrate. The residual streams generated in the process can be used as economic nutrients for the production of xylitol by D. hansenii. Copyright © 2010 Society of Chemical Industry.

  18. [Chiral separation of five beta-blockers using di-n-hexyl L-tartrate-boric acid complex as mobile phase additive by reversed-phase liquid chromatography].

    Science.gov (United States)

    Yang, Juan; Wang, Lijuan; Guo, Qiaoling; Yang, Gengliang

    2012-03-01

    A reversed-phase high performance liquid chromatographic (HPLC) method using the di-n-hexyl L-tartrate-boric acid complex as a chiral mobile phase additive was developed for the enantioseparation of five beta-blockers including propranolol, esmolol, metoprolol, bisoprolol and sotalol. In order to obtain a better enantioseparation, the influences of concentrations of di-n-butyl L-tartrate and boric acid, the type, concentration and pH of the buffer, methanol content as well as the molecular structure of analytes were extensively investigated. The separation of the analytes was performed on a Venusil MP-C18 column (250 mm x 4.6 mm, 5 microm). The mobile phase was 15 mmol/L ammonium acetate-methanol containing 60 mmol/L boric acid, 70 mmol/L di-n-hexyl L-tartrate (pH 6.00). The volume ratios of 15 mmol/L ammonium acetate to methanol were 20: 80 for propranolol, esmolol, metoprolol, bisoprolol and 30: 70 for sotalol. The flow rate was 0.5 mL/min and the detection wavelength was set at 214 nm. Under the optimized conditions, baseline enantioseparation was obtained separately for the five pairs of analytes.

  19. 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

  20. 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

  1. 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

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

  5. 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.

  6. Efficacy of brimonidine tartrate 0.2% ophthalmic solution in reducing halos after laser in situ keratomileusis.

    Science.gov (United States)

    Lee, Ji Hoon; You, Yong Sung; Choe, Chul Myong; Lee, Eun Suk

    2008-06-01

    To quantitatively evaluate the effect of brimonidine tartrate 0.2% (Alphagan) on halo and pupil size in patients who had symptomatic night-vision difficulties after laser in situ keratomileusis (LASIK). Nune Eye Hospital, Seoul, Korea. This study comprised 28 eyes of 14 patients with symptomatic night-vision difficulties after LASIK. Pupil diameter was measured with a Colvard pupillometer (Oasis Medical, Inc.). Quantitative analysis of halos was performed by measuring the area using a new computerized method. Pupil size and halo size were evaluated under scotopic and normal room light conditions. Alphagan was administered, and the effect was measured after 30 minutes and 1, 6, 12, and 24 hours. There was a statistically significant correlation between pupil size and halo size (r = 0.527; P<.0001; slope = 691.6 pixel/mm). Pupil size and halo size decreased significantly 30 minutes after Alphagan instillation under both luminance conditions (all P< .0001). Under normal room light, the pupil and halo remained decreased until the last measurement at 24 hours. Under scotopic conditions, the pupil returned to its preinstillation size at 24 hours while the halo remained decreased. The maximum effect on halos was observed after 6 hours, when the mean reduction over preinstillation size was 28.2% and 29.1% under normal room light conditions and scotopic conditions, respectively. Alphagan effectively reduced halo size and pupil size in postoperative LASIK patients with night-vision symptoms.

  7. Optimization of biodiesel production process from soybean oil using the sodium potassium tartrate doped zirconia catalyst under Microwave Chemical Reactor.

    Science.gov (United States)

    Li, Yihuai; Ye, Bin; Shen, Jiaowen; Tian, Zhen; Wang, Lijun; Zhu, Luping; Ma, Teng; Yang, Dongya; Qiu, Fengxian

    2013-06-01

    A solid base catalyst was prepared by the sodium potassium tartrate doped zirconia and microwave assisted transesterification of soybean oil was carried out for the production of biodiesel. It was found that the catalyst of 2.0(n(Na)/n(Zr)) and calcined at 600°C showed the optimum activity. The base strength of the catalysts was tested by the Hammett indicator method, and the results showed that the fatty acid methyl ester (FAME) yield was related to their total basicity. The catalyst was also characterized by FTIR, TGA, XRD and TEM. The experimental results showed that a 2.0:1 volume ratio of methanol to oil, 65°C reaction temperature, 30 min reaction time and 10 wt.% catalyst amount gave the highest the yield of biodiesel. Compared to conventional method, the reaction time of the way of microwave assisted transesterification was shorter. The catalyst had longer lifetime and maintained sustained activity after being used for four cycles. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Assessment the levels of tartrate-resistant acid phosphatase (TRAP) on mice fed with eggshell calcium citrate malate.

    Science.gov (United States)

    Yu, Yiding; Zhang, Mingdi; Lin, Songyi; Wang, Liyan; Liu, Jingbo; Jones, Gregory; Huang, Hsiang-Chi

    2013-07-01

    Optimized conditions were obtained by one-factor-at-a-time test (OFAT) and ternary quadratic regression orthogonal composite design (TQROCD) respectively. By pulse electric fields (PEF) technology, the process of eggshell calcium citrate malate (ESCCM), eggshell calcium citrate (ESCC) and eggshells calcium malate (ESCM) were comprehensive compared. The levels of tartrate-resistant acid phosphatase (TRAP) and the bioavailability on mice fed with eggshell calcium citrate malate (ESCCM) treated by pulsed electric field (PEF) were evaluated. Results showed that the rates of calcium dissolution of the different acids studied can be arranged as ESCCM (7.90 mg/mL)>ESCC (7.12 mg/mL)>ESCM (7.08 mg/mL) from highest to lowest rate of dissolution. At the same dose 133.0 mg kg(-1) d(-1), the levels of TRAP in the ESCCM treatment groups were significantly lower than those in ESCM and ESCC (P<0.05). Bone calcium content in the mice fed with ESCCM was generally higher than fed with ESCM and ESCC. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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. 

  11. 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...

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Improvement in facial erythema within 30 minutes of initial application of brimonidine tartrate in patients with rosacea.

    Science.gov (United States)

    Jackson, J Mark; Fowler, Joseph; Moore, Angela; Jarratt, Michael; Jones, Terry; Meadows, Kappa; Steinhoff, Martin; Rudisill, Diane; Leoni, Matthew

    2014-06-01

    Brimonidine tartrate (BT) 0.5% gel demonstrated significantly greater efficacy versus vehicle gel once-daily for the treatment of moderate to severe erythema of rosacea. To assess the 30-minute speed of onset of topical BT 0.5% gel in reducing facial erythema in Phase III studies as measured by subject and clinician assessments of erythema. Two Phase III, randomized, controlled studies with identical design in which subjects with moderate erythema of rosacea (study A: n=260; study B: n=293) were randomized 1:1 to apply topical BT 0.5% or vehicle gel once-daily for 4 weeks. Evaluations included severity of erythema based on Clinician's Erythema Assessment (CEA) and Patient's Self-Assessment (PSA) prior to study drug application and at 30 minutes after application on days 1, 15, and 29. 97.7% and 96.6% of subjects reported normal study completion for studies A and B, respectively. The percentage of subjects achieving a 1-grade improvement in both CEA and PSA was significantly increased at 30 minutes post-dosing with BT 0.5% gel compared to vehicle gel on visit days (day 1: 27.9 vs 6.9%, P <0.001; day 15: 55.9 vs 21.1%, P <0.001; Day 29: 58.3 vs 32.0%, P <0.001 for BT 0.5% gel vs vehicle) in study A. Similar results were shown for study B. Once-daily topical BT gel 0.5% is not only efficacious at reducing facial erythema but also exhibits response within 30 minutes of application in a significant number of patients throughout both Phase III studies.

  19. Brimonidine tartrate 0.15%, dorzolamide hydrochloride 2%, and brinzolamide 1% compared as adjunctive therapy to prostaglandin analogs.

    Science.gov (United States)

    Bournias, Thomas E; Lai, Jerry

    2009-09-01

    To compare the efficacy of brimonidine, dorzolamide, and brinzolamide in reducing intraocular pressure (IOP) when used as adjunctive therapy to a prostaglandin analog (PGA). Randomized, controlled, investigator-masked, single-site, parallel-group clinical trial. One hundred twenty eyes of 120 patients with open-angle glaucoma or ocular hypertension who had inadequate IOP control after at least 6 weeks of monotherapy with a once-daily PGA (bimatoprost, latanoprost, or travoprost). Study eyes were assigned randomly to adjunctive treatment with thrice-daily brimonidine tartrate 0.15% (n = 41), dorzolamide hydrochloride 2% (n = 40), or brinzolamide 1% (n = 39) for 4 months. Efficacy was evaluated by IOP measured at 10 am and 4 pm at baseline, month 1, and month 4. The mean IOP at each hour at PGA-treated baseline was comparable among treatment groups. After initiation of adjunctive therapy, the mean IOP was lower and the mean change from baseline IOP was greater in the brimonidine group than in either the dorzolamide group or the brinzolamide group at 10 am and 4 pm at months 1 and 4 (Pbrimonidine, 3.4 mmHg (16%) and 2.8 mmHg (14%) with dorzolamide, and 3.4 mmHg (16%) and 2.6 mmHg (13%) with brinzolamide (Pbrimonidine vs. dorzolamide and brinzolamide at each time point). Each of the study drugs was well tolerated, and all patients completed the study. The addition of brimonidine to a PGA provided greater IOP lowering than the addition of either dorzolamide or brinzolamide. Further studies are needed to evaluate the relative long-term efficacy and tolerability of these medications as adjunctive therapy to a PGA. Proprietary or commercial disclosure may be found after the references.

  20. The Role of Topical Brimonidine Tartrate Gel as a Novel Therapeutic Option for Persistent Facial Erythema Associated with Rosacea.

    Science.gov (United States)

    Johnson, Andrew William; Johnson, Sandra Marchese

    2015-09-01

    Rosacea is a chronic inflammatory skin condition that commonly presents with persistent facial erythema with or without the coincident presence of flushing, telangiectasias, inflammatory papules or pustules, phymatous changes, or ocular involvement. Patients often present with a constellation of various signs and symptoms of the disease, and an individualized treatment plan should be tailored to a patient's unique clinical presentation. Previously available medications for rosacea have all targeted the inflammatory erythematous papules and pustules frequently associated with the disease, leaving a therapeutic gap for the common manifestation of persistent facial erythema. Brimonidine tartrate 0.33% gel was approved by the US Food and Drug Administration in August 2013 as the first medication available for the topical treatment of persistent facial erythema associated with rosacea. Brimonidine gel is a highly selective α2-adrenergic receptor agonist with potent vasoconstrictive effects, which leads to significant reduction of persistent facial erythema in the majority of patients when applied once daily. Based on large-scale clinical trials and post-marketing reports, brimonidine gel has maintained a good safety profile with a minority of patients experiencing adverse effects from its use, most of which are cutaneous in nature, mild-to-moderate in degree, occur early after initiation of treatment, often resolve spontaneously with continued use, and generally resolve after discontinuation of use. Among the reported adverse effects, two distinct manifestations of worsened erythema have been described. Brimonidine gel can be integrated into a treatment regimen along with concomitant therapies for facial papules and pustules with no increased risk of adverse events with combination therapy. Education about optimal application methods, setting reasonable expectations for treatment, and minimizing inflammation are important factors for the successful use of brimonidine

  1. Evaluation of Efficacy and Safety of Brimonidine Tartrate Ophthalmic Solution, 0.025% for Treatment of Ocular Redness.

    Science.gov (United States)

    Torkildsen, Gail L; Sanfilippo, Christine M; DeCory, Heleen H; Gomes, Paul J

    2018-01-01

    Purpose/Aims: This study assessed the efficacy and safety of brimonidine tartrate ophthalmic solution, 0.025% for treating ocular redness in adult subjects. This was a single-center, double-masked, randomized, vehicle-controlled, parallel-group study in subjects ≥40 years, with ocular redness. Subjects were randomized 2:1 to brimonidine or vehicle, instilled QID for four weeks. Subjects completed four visits, the last occurring one week after treatment discontinuation. The investigator assessed ocular redness on a scale of 0-4 pre-instillation and 5-240 minutes post-instillation on Day 0, pre-instillation and 5 minutes post-instillation on Days 14 and 28, and on Day35; subjects assessed redness in diaries throughout the 28-day treatment period and following treatment discontinuation. Safety assessments included adverse events (AEs), rebound redness on treatment discontinuation, comprehensive ophthalmic exams, and vital signs. Drop comfort was assessed upon instillation, and 30 seconds and 1 minute post-instillation at Day 0. Fifty-seven subjects (brimonidine, n = 38; vehicle, n = 19) were randomized. Investigator-assessed ocular redness was significantly reduced with brimonidine across the entire post-instillation time period (overall treatment difference: -1.37; P brimonidine (P ≤ 0.0005). No tachyphylaxis was evident. There were few ocular AEs, all mild to moderate in severity, and no redness rebound was observed upon brimonidine discontinuation. There were no effects on any safety measures, and both brimonidine and its vehicle were reported to be very comfortable. Brimonidine 0.025% appeared safe, well tolerated, and reduced ocular redness for at least 4 hours. No tachyphylaxis or rebound redness upon treatment discontinuation was observed.

  2. Pharmacokinetics of butorphanol tartrate in a long-acting poloxamer 407 gel formulation administered to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Laniesse, Delphine; Guzman, David Sanchez-Migallon; Knych, Heather K; Smith, Dale A; Mosley, Cornelia; Paul-Murphy, Joanne R; Beaufrère, Hugues

    2017-06-01

    OBJECTIVE To determine pharmacokinetics of butorphanol tartrate incorporated into poloxamer 407 (P407) after SC administration to Hispaniolan Amazon parrots (Amazona ventralis). ANIMALS 11 adult Hispaniolan Amazon parrots (6 males and 5 females; 11 to 27 years old). PROCEDURES A sterile formulation of butorphanol in P407 (But-P407) 25% (percentage determined as [weight of P407/weight of diluent] × 100]) was created (8.3 mg/mL). Five preliminary experiments (2 birds/experiment) were performed to determine the ideal dose for this species. The formulation then was administered (12.5 mg/kg, SC) to 8 birds. Blood samples were collected before (time 0) and 0.08, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Some birds were used more than once, with a washout period of ≥ 3 months between subsequent treatments. Butorphanol concentrations were quantitated by use of liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed by use of noncompartmental analysis. RESULTS Maximal plasma butorphanol concentration was reached at 1.31 hours. Plasma concentrations of butorphanol remained > 100 ng/mL for > 3 hours (all birds) or > 4 hours (5/8 birds) but parrots, and absorption followed a pharmacokinetic profile compatible with a sustained-release drug. A dose of 12.5 mg/kg, SC, would theoretically provide analgesia for 4 to 8 hours. No adverse effects were detected. Studies on the pharmacodynamics of this formulation are necessary to confirm the degree and duration of analgesia.

  3. Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?

    Directory of Open Access Journals (Sweden)

    Hume David A

    2008-09-01

    Full Text Available Abstract Background Tartrate-resistant acid phosphatases (TRAcPs, also known as purple acid phosphatases (PAPs, are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics. Findings A new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine. Conlusion The gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism.

  4. Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder

    Directory of Open Access Journals (Sweden)

    D. Prasanthi

    2013-01-01

    Full Text Available Purpose The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT transdermal gel and to evaluate its pharmacokinetic properties. Materials and Methods Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats. Results Transdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q24 was 145.71 ± 2.00µg/cm2 by CIT4 formulation over control (91.89 ± 2.30µg/cm2. Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5% and iontophoretic variables applied (0.5mA/cm2 and pulse on/off ratio 3:1 was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides. Conclusion Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder.

  5. Pharmacokinetics of butorphanol tartrate in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus).

    Science.gov (United States)

    Riggs, Shannon M; Hawkins, Michelle G; Craigmill, Arthur L; Kass, Philip H; Stanley, Scott D; Taylor, Ian T

    2008-05-01

    To determine the pharmacokinetics of butorphanol tartrate after IV and IM single-dose administration in red-tailed hawks (RTHs) and great horned owls (GHOs). 6 adult RTHs and 6 adult GHOs. Each bird received an injection of butorphanol (0.5 mg/kg) into either the right jugular vein (IVj) or the pectoral muscles in a crossover study (1-week interval between treatments). The GHOs also later received butorphanol (0.5 mg/kg) via injection into a medial metatarsal vein (IVm). During each 24-hour postinjection period, blood samples were collected from each bird; plasma butorphanol concentrations were determined via liquid chromatography-mass spectrometry. 2- and 1-compartment models best fit the IV and IM pharmacokinetic data, respectively, in both species. Terminal half-lives of butorphanol were 0.94 +/- 0.30 hours (IVj) and 0.94 +/- 0.26 hours (IM) for RTHs and 1.79 +/- 1.36 hours (IVj), 1.84 +/- 1.56 hours (IM), and 1.19 +/- 0.34 hours (IVm) for GHOs. In GHOs, area under the curve (0 to infinity) for butorphanol after IVj or IM administration exceeded values in RTHs; GHO values after IM and IVm administration were less than those after IVj administration. Plasma butorphanol clearance was significantly more rapid in the RTHs. Bioavailability of butorphanol administered IM was 97.6 +/- 33.2% (RTHs) and 88.8 +/- 4.8% (GHOs). In RTHs and GHOs, butorphanol was rapidly absorbed and distributed via all routes of administration; the drug's rapid terminal half-life indicated that published dosing intervals for birds may be inadequate in RTHs and GHOs.

  6. Analgesic effects of butorphanol tartrate and phenylbutazone administered alone and in combination in young horses undergoing routine castration.

    Science.gov (United States)

    Sanz, Macarena G; Sellon, Debra C; Cary, Julie A; Hines, Melissa T; Farnsworth, Kelly D

    2009-11-15

    To compare the analgesic efficacy of administration of butorphanol tartrate, phenylbutazone, or both drugs in combination in colts undergoing routine castration. Randomized controlled clinical trial. 36 client-owned colts. Horses received treatment with butorphanol alone (0.05 mg/kg [0.023 mg/lb], IM, prior to surgery and then q 4 h for 24 hours), phenylbutazone alone (4.4 mg/kg [2.0 mg/lb], IV, prior to surgery and then 2.2 mg/kg [1.0 mg/lb], PO, q 12 h for 3 days), or butorphanol and phenylbutazone at the aforementioned dosages (12 horses/group). For single-drug-treated horses, appropriate placebos were administered to balance treatment protocols among groups. All horses were anesthetized, and lidocaine hydrochloride was injected into each testis. Physical and physiological variables, plasma cortisol concentration, body weight, and water consumption were assessed before and at intervals after surgery, and induction of and recovery from anesthesia were subjectively characterized. Observers assessed signs of pain by use of a visual analogue scale and a numerical rating scale. Significant changes in gastrointestinal sounds, fecal output, and plasma cortisol concentrations were evident in each treatment group over time, compared with preoperative values. At any time point, assessed variables and signs of pain did not differ significantly among groups, although the duration of recumbency after surgery was longest for the butorphanol-phenylbutazone-treated horses. With intratesticular injections of lidocaine, administration of butorphanol to anesthetized young horses undergoing routine castration had the same apparent analgesic effect as phenylbutazone treatment. Combined butorphanolphenylbutazone treatment was not apparently superior to either drug used alone.

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

    Science.gov (United States)

    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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Risk assessment of "other substances" – L-Carnitine and L-Carnitine-L-tartrate. Opinion of the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food Safety

    OpenAIRE

    Bruzell, Ellen Merete; Granum, Berit; Hetland, Ragna Bogen; Husøy, Trine; Rohloff, Jens; Wicklund, Trude; Steffensen, Inger-Lise

    2015-01-01

    The Norwegian Scientific Committee for Food Safety (VKM) has, at the request of the Norwegian Food Safety Authority (NFSA), assessed the risk of 1500 mg/day of L-carnitine and 2250 mg/day of L-carnitine-L-tartrate in food supplements. L-carnitine occurs naturally in foods and is endogenously synthesised. L-carnitine-L-tartrate is synthesised commercially, and it dissociates into L-carnitine and tartaric acid in the gastrointestinal tract. Based on the included literature there was no evid...

  16. 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

  17. 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

  18. 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

  19. Preparative enantioseparation of propafenone by counter-current chromatography using di-n-butyl L-tartrate combined with boric acid as the chiral selector.

    Science.gov (United States)

    Tong, Shengqiang; Shen, Mangmang; Zheng, Ye; Chu, Chu; Li, Xing-Nuo; Yan, Jizhong

    2013-09-01

    This paper extends the research of the utilization of borate coordination complexes in chiral separation by counter-current chromatography (CCC). Racemic propafenone was successfully enantioseparated by CCC with di-n-butyl l-tartrate combined with boric acid as the chiral selector. The two-phase solvent system was composed of chloroform/ 0.05 mol/L acetate buffer pH 3.4 containing 0.10 mol/L boric acid (1:1, v/v), in which 0.10 mol/L di-n-butyl l-tartrate was added in the organic phase. The influence of factors in the enantioseparation of propafenone were investigated and optimized. A total of 92 mg of racemic propafenone was completely enantioseparated using high-speed CCC in a single run, yielding 40-42 mg of (R)- and (S)-propafenone enantiomers with an HPLC purity over 90-95%. The recovery for propafenone enantiomers from fractions of CCC was in the range of 85-90%. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 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.

  1. 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.

  2. [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.

  3. 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.

  4. 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.

  5. 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

  6. 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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

  8. 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

  9. The efficacy and safety of add-on 0.1% brimonidine tartrate preserved with sodium chlorite in on-treatment Japanese normal-tension glaucoma patients [Corrigendum

    Directory of Open Access Journals (Sweden)

    Tsumura T

    2015-07-01

    Full Text Available The efficacy and safety of add-on 0.1% brimonidine tartrate preserved with sodium chlorite in on-treatment Japanese normal-tension glaucoma patients [Corrigendum] Tsumura T, Yoshikawa K, Kimura T, et al. Clin Ophthalmol. 2014;8:1681–1687. The authors wish to advise of the following errors: on page 1684, right column, line 18, “10.72” should be replaced with “–10.72”; on page 1685, right column, line 2, “<–6D” should be replaced with “<–6dB”. Read the original article Previous corrigendum has been published

  10. Thermodynamic study of binary system Propafenone Hydrocloride with Metoprolol Tartrate: solid-liquid equilibrium and compatibility with α-lactose monohydrate and corn starch.

    Science.gov (United States)

    Marinescu, Daniela-Crina; Pincu, Elena; Meltzer, Viorica

    2013-05-20

    Solid-liquid equilibrium (SLE) for binary mixture of Propafenone Hydrocloride (PP) with Metoprolol Tartrate (MT) was investigated using differential scanning calorimetry (DSC) and corresponding activity coefficients were calculated. Simple eutectic behavior for this system was observed. The excess thermodynamic functions: G(E) and S(E) for the pre-, post-, and eutectic composition have been obtained using the computed activity coefficients data of the eutectic phase with their excess chemical potentials μi(E) (i=1, 2). The experimental solid-liquid phase temperatures were compared with predictions obtained from available eutectic equilibrium models. The results indicate non-ideality in this mixture. Also, the compatibility of each component and their eutectic mixture with usual excipients was investigated, and the DSC experiments indicate possible weak interactions with α-lactose monohydrate and compatibility with corn starch. The results obtained were confirmed by FT-IR measurements. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Photocatalytic degradation of metoprolol tartrate in suspensions of two TiO{sub 2}-based photocatalysts with different surface area. Identification of intermediates and proposal of degradation pathways

    Energy Technology Data Exchange (ETDEWEB)

    Abramovic, Biljana, E-mail: biljana.abramovic@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Kler, Sanja, E-mail: sanja.kler@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Sojic, Daniela, E-mail: daniela.sojic@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Lausevic, Mila, E-mail: milal@tmf.bg.ac.rs [Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11120 Belgrade (Serbia); Radovic, Tanja, E-mail: tradovic@tmf.bg.ac.rs [Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11120 Belgrade (Serbia); Vione, Davide, E-mail: davide.vione@unito.it [Dipartimento di Chimica Analitica, Universita di Torino, Via Pietro Giuria 5, 10125 Torino (Italy)

    2011-12-30

    Highlights: Black-Right-Pointing-Pointer Kinetics and efficiency of photocatalytic degradation of the {beta}{sub 1}-blocker metoprolol tartrate (MET). Black-Right-Pointing-Pointer Two TiO{sub 2} specimens employed. Black-Right-Pointing-Pointer Faster degradation of MET, but slower mineralization, obtained with the TiO{sub 2} specimen having lower surface area. Black-Right-Pointing-Pointer Photocatalytic transformation pathways of MET including mineralization. - Abstract: This study investigates the efficiency of the photocatalytic degradation of metoprolol tartrate (MET), a widely used {beta}{sub 1}-blocker, in TiO{sub 2} suspensions of Wackherr's 'Oxyde de titane standard' and Degussa P25. The study encompasses transformation kinetics and efficiency, identification of intermediates and reaction pathways. In the investigated range of initial concentrations (0.01-0.1 mM), the photocatalytic degradation of MET in the first stage of the reaction followed approximately a pseudo-first order kinetics. The TiO{sub 2} Wackherr induced a significantly faster MET degradation compared to TiO{sub 2} Degussa P25 when relatively high substrate concentrations were used. By examining the effect of ethanol as a scavenger of hydroxyl radicals ({center_dot}OH), it was shown that the reaction with {center_dot}OH played the main role in the photocatalytic degradation of MET. After 240 min of irradiation the reaction intermediates were almost completely mineralized to CO{sub 2} and H{sub 2}O, while the nitrogen was predominantly present as NH{sub 4}{sup +}. Reaction intermediates were studied in detail and a number of them were identified using LC-MS/MS (ESI+), which allowed the proposal of a tentative pathway for the photocatalytic transformation of MET as a function of the TiO{sub 2} specimen.

  12. Crystal structure of the NADP+and tartrate-bound complex of L-serine 3-dehydrogenase from the hyperthermophilic archaeon Pyrobaculum calidifontis.

    Science.gov (United States)

    Yoneda, Kazunari; Sakuraba, Haruhiko; Araki, Tomohiro; Ohshima, Toshihisa

    2018-01-20

    A gene encoding L-serine dehydrogenase (L-SerDH) that exhibits extremely low sequence identity to the Agrobacterium tumefaciens L-SerDH was identified in the hyperthermophilic archaeon Pyrobaculum calidifontis. The predicted amino acid sequence showed 36% identity with that of Pseudomonas aeruginosa L-SerDH, suggesting that P. calidifontis L-SerDH is a novel type of L-SerDH, like Ps. aeruginosa L-SerDH. The overexpressed enzyme appears to be the most thermostable L-SerDH described to date, and no loss of activity was observed by incubation for 30 min at temperatures up to 100 °C. The enzyme showed substantial reactivity towards D-serine, in addition to L-serine. Two different crystal structures of P. calidifontis L-SerDH were determined using the Se-MAD and MR method: the structure in complex with NADP + /sulfate ion at 1.18 Å and the structure in complex with NADP + /L-tartrate (substrate analog) at 1.57 Å. The fold of the catalytic domain showed similarity with that of Ps. aeruginosa L-SerDH. However, the active site structure significantly differed between the two enzymes. Based on the structure of the tartrate, L- and D-serine and 3-hydroxypropionate molecules were modeled into the active site and the substrate binding modes were estimated. A structural comparison suggests that the wide cavity at the substrate binding site is likely responsible for the high reactivity of the enzyme toward both L- and D-serine enantiomers. This is the first description of the structure of the novel type of L-SerDH with bound NADP + and substrate analog, and it provides new insight into the substrate binding mechanism of L-SerDH. The results obtained here may be very informative for the creation of L- or D-serine-specific SerDH by protein engineering.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. The efficacy and safety of add-on 0.1% brimonidine tartrate preserved with sodium chlorite in on-treatment Japanese normal-tension glaucoma patients

    Directory of Open Access Journals (Sweden)

    Tsumura T

    2014-09-01

    Full Text Available Toyoaki Tsumura,1 Keiji Yoshikawa,2 Tairo Kimura,3 Hirotaka Suzumura,4 Miwako Kawashima,5 Mami Nanno,6 Kiyotaka Ishijima,7 Ryuji Takeda8 1Fussa Hospital, Tokyo, Japan; 2Yoshikawa Eye Clinic, Tokyo, Japan; 3Ueno Eye Clinic, Tokyo, Japan; 4Suzumura Eye Clinic, Tokyo, Japan; 5Nakano General Hospital, Tokyo, Japan; 6Kagurazaka Minamino Eye Clinic, Tokyo, Japan; 7Irumagawa Hospital, Saitama, Japan; 8Department of Biological Chemistry, Faculty of Agriculture, Kinki University, Nara, Japan Background: To evaluate the efficacy and safety of newly formulated brimonidine (0.1% brimonidine tartrate preserved with sodium chlorite: brimonidine as add-on therapy in on-treatment Japanese normal-tension glaucoma (NTG patients.Methods: Brimonidine was added to on-treatment NTG patients with intraocular pressures (IOP of between 13 mmHg and 16 mmHg after three consecutive IOP measurements. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 4, 8, and 12 weeks after brimonidine instillation.Results: Though 75 of 83 patients (31 males and 52 females; mean age: 63.4±11.6 years completed the study, six patients discontinued because of side effects and two patients withdrew. The mean IOP after brimonidine addition at week 4 (12.6±1.8 mmHg, P<0.001, week 8 (12.4±1.7 mmHg, P<0.001, and week 12 (12.6±1.8 mmHg, P<0.001 was significantly decreased compared with that before the addition of brimonidine (13.9±1.2 mmHg. No significant changes in superficial punctate keratitis or conjunctival hyperemia scores were observed throughout the study. Dizziness, sleepiness, eye pain, and itching (mild to moderate were noted in five, four, three, and three patients, respectively.Conclusions: The addition of newly formulated brimonidine to on-treatment Japanese NTG patients with IOP of 13–16 mmHg further reduced the levels of IOP with minimal side effects and adverse events. Keywords: normal-tension glaucoma, 0

  11. An ion-pair principle for enantioseparations of basic analytes by nonaqueous capillary electrophoresis using the di-n-butyl L-tartrate-boric acid complex as chiral selector.

    Science.gov (United States)

    Wang, Li-Juan; Liu, Xiu-Feng; Lu, Qie-Nan; Yang, Geng-Liang; Chen, Xing-Guo

    2013-04-05

    A chiral recognition mechanism of ion-pair principle has been proposed in this study. It rationalized the enantioseparations of some basic analytes using the complex of di-n-butyl l-tartrate and boric acid as the chiral selector in methanolic background electrolytes (BGEs) by nonaqueous capillary electrophoresis (NACE). An approach of mass spectrometer (MS) directly confirmed that triethylamine promoted the formation of negatively charged di-n-butyl l-tartrate-boric acid complex chiral counter ion with a complex ratio of 2:1. And the negatively charged counter ion was the real chiral selector in the ion-pair principle enantioseparations. It was assumed that triethylamine should play its role by adjusting the apparent acidity (pH*) of the running buffer to a higher value. Consequently, the effects of various basic electrolytes including inorganic and organic ones on the enantioseparations in NACE were investigated. The results showed that most of the basic electrolytes tested were favorable for the enantioseparations of basic analytes using di-n-butyl l-tartrate-boric acid complex as the chiral ion-pair selector. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. 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.

  13. 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

  14. The efficacy and safety of add-on 0.1% brimonidine tartrate preserved with sodium chlorite in on-treatment Japanese normal-tension glaucoma patients.

    Science.gov (United States)

    Tsumura, Toyoaki; Yoshikawa, Keiji; Kimura, Tairo; Suzumura, Hirotaka; Kawashima, Miwako; Nanno, Mami; Ishijima, Kiyotaka; Takeda, Ryuji

    2014-01-01

    To evaluate the efficacy and safety of newly formulated brimonidine (0.1% brimonidine tartrate preserved with sodium chlorite: brimonidine) as add-on therapy in on-treatment Japanese normal-tension glaucoma (NTG) patients. Brimonidine was added to on-treatment NTG patients with intraocular pressures (IOP) of between 13 mmHg and 16 mmHg after three consecutive IOP measurements. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 4, 8, and 12 weeks after brimonidine instillation. Though 75 of 83 patients (31 males and 52 females; mean age: 63.4±11.6 years) completed the study, six patients discontinued because of side effects and two patients withdrew. The mean IOP after brimonidine addition at week 4 (12.6±1.8 mmHg, Psuperficial punctate keratitis or conjunctival hyperemia scores were observed throughout the study. Dizziness, sleepiness, eye pain, and itching (mild to moderate) were noted in five, four, three, and three patients, respectively. The addition of newly formulated brimonidine to on-treatment Japanese NTG patients with IOP of 13-16 mmHg further reduced the levels of IOP with minimal side effects and adverse events.

  15. Formulation and ex vivo-in vivo evaluation of pH-triggered brimonidine tartrate in situ gel for the glaucoma treatment using application of 32 factorial design.

    Science.gov (United States)

    Barse, Rohan K; Tagalpallewar, Amol A; Kokare, Chandrakant R; Sharma, Jaya P; Sharma, Pankaj K

    2017-12-19

    Short residence time, poor bioavailability and poor permeability are the major problems for conventional eye drops treatment. The aim of this article is to develop, optimize and ex vivo-in vivo investigation of brimonidine tartrate in situ gel as compared to marketed eye drops for the treatment of glaucoma. The effect of independent variables, namely concentrations of polymers, on various dependent variables like viscosity at physiological pH and in vitro drug release were studied by using 32 factorial design. Further the optimized formulation was characterized for ex vivo and in vivo study. Experimental data demonstrated that optimized in situ gel formulation (F8) showed in vitro-ex vivo sustained release profile with polymer composites carbopol 974P and HPMC K4M. After 5 h of ex vivo transcorneal permeation study, the amount recovered from the corneal surface on the donor chamber 12.40% (124 ug) and the amount collected from the receptor chamber 76.8% (760 ug) of the initial dose 1 mg. The total amount recovered from the permeation experiment was 89.2%. Bioadhesive carbopol 974P and viscosity HPMC K4M composites optimized formulation (F 8) produce greater influence on the duration of drug action and improved intraocular pressure reduction activity as compared to marketed eye drop solution in in vivo study. The developed in situ gelling system as a promising ophthalmic formulation to prolong the drug lowering effect on the intraocular pressure.

  16. Intraocular pressure reduction using a fixed combination of timolol maleate 0.5% and brimonidine tartrate 0.2% administered three times daily

    Directory of Open Access Journals (Sweden)

    Moisseiev E

    2013-06-01

    Full Text Available Elad Moisseiev, Shimon Kurtz, Moshe Lazar, Gabi ShemeshDepartment of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelBackground: The purpose of this study was to evaluate the safety and efficacy of a fixed combination of timolol maleate 0.5% + brimonidine tartrate 0.2% (Combigan® for reduction for intraocular pressure (IOP in patients with glaucoma when the dose frequency is increased from twice to three times daily.Methods: The patients included had either primary open angle glaucoma or ocular hypertension. Those who were previously on treatment completed a drug washout period prior to inclusion. IOP was measured at baseline, after 4 weeks of treatment with Combigan twice daily, and again after a further 4 weeks of Combigan three times daily. Blood pressure, heart rate, and oxygen saturation were also recorded at each assessment.Results: Thirty-one eyes from 31 patients were included. Increasing the Combigan dose frequency resulted in a statistically significant (P < 0.001 additional reduction in IOP of 2.25 ± 1.18 mmHg, corresponding to a further 10.3% reduction in IOP from baseline. No local or systemic adverse effects were documented.Conclusion: Treatment with Combigan three times daily was more effective in reducing IOP than the twice-daily regimen, with no increase in adverse effects.Keywords: Combigan®, timolol, brimonidine, glaucoma, dose frequency

  17. A New UPLC Method with Chemometric Design-Optimization Approach for the Simultaneous Quantitation of Brimonidine Tartrate and Timolol Maleate in an Eye Drop Preparation.

    Science.gov (United States)

    Büker, Eda; Dinç, Erdal

    2017-02-01

    A new ultra-performance liquid chromatography (UPLC) with photodiode array was proposed for the quantitation of Brimonidine Tartrate (BRI) and Timolol Maleate (TIM) in eye drop using experimental design and optimization methodology. A 33 full factorial design was applied to uncover the effects of the selected factors and their interactions on the chromatographic response function for the optimization of experimental conditions in the development of a new UPLC method. As a result, the optimal chromatographic conditions giving a better separation and short analysis time were found to be 49.2°C for column temperature; 0.38 mL/min for flow rate and 56.7 % (v/v) for 0.1 M CH3COOH used in mobile phase. The elution of BRI and TIM was reported as 0.508 and 0.652 min within a short runtime of 1.5 min, respectively. Calibration graphs for BRI and TIM were obtained by the regression of the concentration on the peak area, which was detected at 246 and 298 nm, respectively. The method validation was performed by the analysis of the synthetic mixtures, intra-day and inter-day samples and standard addition samples. This study shows that the optimized and validated UPLC method is very promising and available for the quantification of BRI and TIM in an eye drop formulation. © Crown copyright 2016.

  18. Intraocular pressure reduction using a fixed combination of timolol maleate 0.5% and brimonidine tartrate 0.2% administered three times daily

    Science.gov (United States)

    Moisseiev, Elad; Kurtz, Shimon; Lazar, Moshe; Shemesh, Gabi

    2013-01-01

    Background The purpose of this study was to evaluate the safety and efficacy of a fixed combination of timolol maleate 0.5% + brimonidine tartrate 0.2% (Combigan®) for reduction for intraocular pressure (IOP) in patients with glaucoma when the dose frequency is increased from twice to three times daily. Methods The patients included had either primary open angle glaucoma or ocular hypertension. Those who were previously on treatment completed a drug washout period prior to inclusion. IOP was measured at baseline, after 4 weeks of treatment with Combigan twice daily, and again after a further 4 weeks of Combigan three times daily. Blood pressure, heart rate, and oxygen saturation were also recorded at each assessment. Results Thirty-one eyes from 31 patients were included. Increasing the Combigan dose frequency resulted in a statistically significant (P < 0.001) additional reduction in IOP of 2.25 ± 1.18 mmHg, corresponding to a further 10.3% reduction in IOP from baseline. No local or systemic adverse effects were documented. Conclusion Treatment with Combigan three times daily was more effective in reducing IOP than the twice-daily regimen, with no increase in adverse effects. PMID:23836956

  19. Preparation of green alga-based activated carbon with lower impregnation ratio and less activation time by potassium tartrate for adsorption of chloramphenicol.

    Science.gov (United States)

    Zhu, Xiuzhen; Gao, Yuan; Yue, Qinyan; Kan, Yujiao; Kong, Wenjia; Gao, Baoyu

    2017-11-01

    Potassium tartrate (C 4 H 6 K 2 O 7 ) was utilized as a novel activating agent to prepare activated carbon with relatively high specific surface area by using less activating agent and activation time from marine waste-green alga (Enteromorpha prolifera) for the first time. The influences of activation temperature, impregnation ratio and activation time on the pore structure were investigated to obtain the optimum conditions (activation temperature: 700°C, impregnation ratio: 1:1, and activation time: 30min). Meanwhile, the activation temperature was evaluated to be the essential factor that dominated the form of pore structure in activated carbon. The green alga-based activated carbon that was prepared under optimum conditions has shown the high surface area of 1692m 2 /g and total pore volume of 1.22cm 3 /g, which could be used as an effective adsorbent to remove chloramphenicol. The thermodynamic data of chloramphenicol were well fitted by Langmuir isotherm model and the green alga-based activated carbon has showed high adsorption capacity of 709.2mg/g towards chloramphenicol. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Stearic acid and high molecular weight PEO as matrix for the highly water soluble metoprolol tartrate in continuous twin-screw melt granulation.

    Science.gov (United States)

    Monteyne, Tinne; Adriaensens, Peter; Brouckaert, Davinia; Remon, Jean-Paul; Vervaet, Chris; De Beer, Thomas

    2016-10-15

    Granules with release-sustaining properties were developed by twin screw hot melt granulation (HMG) using a combination of stearic acid (SA) and high molecular weight polyethylene oxide (PEO) as matrix for a highly water soluble model drug, metoprolol tartrate (MPT). Earlier studies demonstrated that mixing molten SA and PEO resulted in hydrogen bond formation between hydroxyl groups of fatty acid molecules and ether groups in PEO chains. These molecular interactions might be beneficial in order to elevate the sustained release effect of drugs from a SA/PEO matrix. This study aims to investigate the continuous twin screw melt granulation technique to study the impact of a SA/PEO matrix on the dissolution rate of a highly water soluble drug (MPT). Decreasing the SA/PEO ratio improved the release-sustaining properties of the matrix. The solid state of the granules was characterized using differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared (FTIR) and near infrared chemical imaging (NIR-CI) in order to understand the dissolution behavior. The results revealed a preferential interaction of the MPT molecules with stearic acid impeding the PEO to form hydrogen bonds with the stearic acid chains. However, this allowed the PEO chains to recrystallize inside the stearic acid matrix after granulation, hence, elevating the release-sustaining characteristics of the formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A Novel Active Targeting Preparation, Vinorelbine Tartrate (VLBT Encapsulated by Folate-Conjugated Bovine Serum Albumin (BSA Nanoparticles: Preparation, Characterization and in Vitro Release Study

    Directory of Open Access Journals (Sweden)

    Xinyang Yu

    2012-11-01

    Full Text Available Vinorelbine tartrate (VLBT, as a kind of high hydrophilic and temperature-induced degradation drug, was prepared into nanoparticles by a desolvation procedure. Bovine serum albumin (BSA, as a drug carrier, was stabilized by chemical cross-linking with glutaraldehyde. Firstly, the optimization process of preparing VLBT-loaded BSA nanoparticles (VLBT-BSANPs was accomplished using response surface methodology (RSM by desolvation. Then VLBT-BSANPs were conjugated with folate, namely Fa-BSANPs-VLBT. Hence targeting drug carrier delivery system loading VLBT was produced. In this study, the characteristics of the nanoparticles, such as the amount of folate conjugation, surface morphology, surface chemistry, physical status of VLBT in Fa-BSANPs-VLBT, stability of Fa-BSANPs-VLBT with mannitol and in vitro drug release behavior were all investigated. The VLBT-BSANPs were obtained under optimum conditions, with a mean particle size (MPS of 155.4 nm and a zeta potential (ZP of −32.97 mV at a pH value of 5.4. Drug loading efficiency (DLE and drug entrapment efficiency (DEE of this obtained drug were approximately 45.6% and 90.6%, respectively.

  2. Analytical method (HPLC, validation used for identification and assay of the pharmaceutical active ingredient, Tylosin tartrate for veterinary use and its finite product Tilodem 50, hydrosoluble powder

    Directory of Open Access Journals (Sweden)

    Maria Neagu

    2010-12-01

    Full Text Available In SC DELOS IMPEX ’96 SRL the quality of the active pharmaceutical ingredient (API for the finite product Tilodem 50 - hydrosoluble powder was acomkplished in the respect of last European Pharmacopoeia.The method for analysis used in this purpose was the compendial method „Tylosin tartrate for veterinary use” in EurPh. in vigour edition and represent a variant developed and validation „in house”.The parameters which was included in the methodology validation for chromatographic method are the followings: Selectivity, Linearity, Linearity range, Detection and Quantification limits, Precision, Repeatability (intra day, Inter-Day Reproductibility, Accuracy, Robustness, Solutions’ stability and System suitability. According to the European Pharmacopoeia, the active pharmaceutical ingredient is consistent, in terms of quality, if it contains Tylosin A - minimum 80% and the amount of Tylosin A, B, C, D, at minimum 95%. Identification and determination of each component separately (Tylosin A, B, C, D is possible by chromatographic separation-HPLC. Validation of analytical methods is presented below.

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Validated spectrofluorimetric and spectrophotometric methods for the determination of brimonidine tartrate in ophthalmic solutions via derivatization with NBD-Cl. Application to stability study.

    Science.gov (United States)

    Ibrahim, F; El-Enany, N; El-Shaheny, R N; Mikhail, I E

    2015-05-01

    Two simple, selective and accurate methods were developed and validated for the determination of brimonidine tartrate (BT) in pure state and pharmaceutical formulations. Both methods are based on the coupling of the drug with 4-chloro-7-nitro-2,1,3-benzoxadiazole in borate buffer (pH 8.5) at 70 °C and measurement of the reaction product spectrophotometrically at 407 nm (method I) or spectrofluorimetrically at 528 nm upon excitation at 460 nm (method II). The calibration graphs were rectilinear over the concentration ranges of 1.0-16.0 and 0.1-4.0 µg/mL with lower detection limits of 0.21 and 0.03, and lower quantification limits of 0.65 and 0.09 µg/mL for methods I and II, respectively. Both methods were successfully applied to the analysis of commercial ophthalmic solution with mean recovery of 99.50 ± 1.00 and 100.13 ± 0.71%, respectively. Statistical analysis of the results obtained by the proposed methods revealed good agreement with those obtained using a comparison method. The proposed spectrofluorimetric method was extended to a stability study of BT under different ICH-outlined conditions such as alkaline, acidic, oxidative and photolytic degradation. Furthermore, the kinetics of oxidative degradation of the drug was investigated and the apparent first-order reaction rate constants, half-life times and Arrhenius equation were estimated. The proposed methods are practical and valuable for routine applications in quality control laboratories for the analysis of BT. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Treatment of facial erythema in patients with rosacea with topical brimonidine tartrate: correlation of patient satisfaction with standard clinical endpoints of improvement of facial erythema.

    Science.gov (United States)

    Fowler, J; Tan, J; Jackson, J M; Meadows, K; Jones, T; Jarratt, M; Leoni, M

    2015-03-01

    Once-daily brimonidine tartrate (BT) 0.5% gel was shown to provide significantly greater efficacy vs. vehicle for the treatment of facial erythema in patients with rosacea. To demonstrate that patient satisfaction with overall appearance is correlated with reduction in facial erythema, as measured by clinician and patient assessments. Data from two identical phase III, multicentre, randomized, controlled trials of moderate facial erythema of rosacea (study A: n = 260; study B: n = 293) with topical BT 0.5% compared to vehicle gel once-daily for 4 weeks were analysed. Correlations of Patient's Assessment of Appearance (PAA) with Clinician's Erythema Assessment (CEA) and Patient's Self-Assessment (PSA) of erythema were evaluated by calculation of gamma statistics. PAA correlated with CEA post-application on Days 1, 15 and 29 for the intent-to-treat population and provided a median gamma value of 0.57 (min = 0.28, max = 0.61). PAA and PSA was also highly correlated post-application on Days 1, 15 and 29; with a median gamma value of 0.87 (min = 0.66, max = 0.89). Subjects who achieved a clinically meaningful improvement in both CEA and PSA scales were more likely to report satisfaction with the overall appearance of their skin (P < 0.001). Both one- and two-grade improvements in facial erythema assessed by subjects (PSA) and clinicians (CEA) correlate well with PAA, a patient-centered representation of meaningful change. © 2014 European Academy of Dermatology and Venereology.

  12. Human infections attributable to the D-tartrate-fermenting variant of Salmonella enterica serovar Paratyphi B in Germany originate in reptiles and, on rare occasions, poultry.

    Science.gov (United States)

    Toboldt, Anne; Tietze, Erhard; Helmuth, Reiner; Fruth, Angelika; Junker, Ernst; Malorny, Burkhard

    2012-10-01

    In this study, the population structure, incidence, and potential sources of human infection caused by the d-tartrate-fermenting variant of Salmonella enterica serovar Paratyphi B [S. Paratyphi B (dT+)] was investigated. In Germany, the serovar is frequently isolated from broilers. Therefore, a selection of 108 epidemiologically unrelated S. enterica serovar Paratyphi B (dT+) strains isolated in Germany between 2002 and 2010 especially from humans, poultry/poultry meat, and reptiles was investigated by phenotypic and genotypic methods. Strains isolated from poultry and products thereof were strongly associated with multilocus sequence type ST28 and showed antimicrobial multiresistance profiles. Pulsed-field gel electrophoresis XbaI profiles were highly homogeneous, with only a few minor XbaI profile variants. All strains isolated from reptiles, except one, were strongly associated with ST88, another distantly related type. Most of the strains were susceptible to antimicrobial agents, and XbaI profiles were heterogeneous. Strains isolated from humans yielded seven sequence types (STs) clustering in three distantly related lineages. The first lineage, comprising five STs, represented mainly strains belonging to ST43 and ST149. The other two lineages were represented only by one ST each, ST28 and ST88. The relatedness of strains based on the pathogenicity gene repertoire (102 markers tested) was mostly in agreement with the multilocus sequence type. Because ST28 was frequently isolated from poultry but rarely in humans over the 9-year period investigated, overall, this study indicates that in Germany S. enterica serovar Paratyphi B (dT+) poses a health risk preferentially by contact with reptiles and, to a less extent, by exposure to poultry or poultry meat.

  13. Antinociceptive effects of intravenous administration of hydromorphone hydrochloride alone or followed by buprenorphine hydrochloride or butorphanol tartrate to healthy conscious cats.

    Science.gov (United States)

    Simon, Bradley T; Steagall, Paulo V; Monteiro, Beatriz P; Troncy, Eric; Lizarraga, Ignacio

    2016-03-01

    To evaluate antinociceptive effects of IV administration of hydromorphone alone or followed by buprenorphine or butorphanol to cats. 6 healthy adult cats. In a randomized, blinded crossover design, cats received each of 4 treatments in which 2 IV injections were given 30 minutes apart: 2 of saline (0.9% NaCl) solution (Sal-Sal) or 1 each of hydromorphone HCl and saline solution (H-Sal), hydromorphone and buprenorphine HCl (H-Bupre), or hydromorphone and butorphanol tartrate (H-Butor). Skin temperature and thermal threshold were recorded before (baseline) and for 12 hours after the first injection. Percentage of maximum possible effect (%MPE) and thermal excursion (TE) were compared among treatments and measurement points. Compared with baseline values, skin temperature was higher from 0.75 to 2 hours after the first injection for H-Sal; at 0.5, 1, 3, and 4 hours for H-Bupre; from 0.5 to 3 hours for H-Butor; and from 0.5 to 1 hours for Sal-Sal. Thermal excursion was higher than at baseline from 0.25 to 2 hours for H-Sal and H-Bupre and 0.25 to 0.75 hours for H-Butor; %MPE increased from 0.25 to 2 hours for H-Sal, 0.25 to 3 hours for H-Bupre, and 0.25 to 0.75 hours for H-Butor. Results were similar for comparisons with Sal-Sal, except TE was greater for H-Sal versus Sal-Sal and TE and %MPE were greater for H-Bupre versus Sal-Sal from 0.25 to 1 hours after the first injection. Butorphanol administration decreased the duration of antinociception achieved with hydromorphone administration in cats. This opioid interaction and its impact on pain management require additional investigation.

  14. Tartrate-Resistant Acid Phosphatase 5b in Young Patients With Sickle Cell Disease and Trait Siblings: Relation to Vasculopathy and Bone Mineral Density.

    Science.gov (United States)

    Mokhtar, Galila Mohamed; Tantawy, Azza Abdel Gawad; Hamed, Ahmed Al-Saeed; Adly, Amira Abdel Moneam; Ismail, Eman Abdel Rahman; Makkeyah, Sara Mostafa

    2017-01-01

    Bone involvement is a frequent cause of acute morbidity in sickle cell disease (SCD). Tartrate-resistant acid phosphatase 5b (TRACP 5b), a bone resorption marker, is produced specifically by activated osteoclasts. We assessed bone mineral density (BMD) in 30 young patients with SCD and 17 asymptomatic patients with sickle cell trait (SCT) compared with 32 healthy controls and determined TRACP 5b levels in relation to vascular complications. Serum ferritin, alkaline phosphatase (ALP), and TRACP 5b were measured. Echocardiography was performed with assessment of BMD using dual energy X-ray absorptiometry (DXA). The BMD was decreased in patients with SCD compared with SCT and controls (P = .005), with no significant difference between the latter 2 groups. Patients with SCD had higher incidence of bone complications than SCT group and controls (P = .03). The SCD group with abnormal DXA scan had higher ferritin and ALP than normal BMD. Serum TRACP 5b was significantly higher in patients with SCD than SCT and controls (P = .003). The TRACP 5b levels were associated with severe vaso-occlusive crisis (P = .022). Patients treated with hydroxyurea and those on chelation therapy had lower TRACP 5b levels than untreated patients. The TRACP 5b level was positively correlated with lactate dehydrogenase, while there was no relation with ferritin, ALP, or BMD. We suggest that bone complications frequently occur in SCD as reflected by low BMD and high ALP and TRACP 5b. Hemolysis and iron overload may be involved in the occurrence of these complications. The lack of correlation between abnormal DXA scan and high TRACP 5b suggests that bone disease in SCD is multifactorial. © The Author(s) 2015.

  15. 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

  16. 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.

  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. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Bis(melaminium tartrate dihydrate

    Directory of Open Access Journals (Sweden)

    Hong Su

    2009-04-01

    Full Text Available In the title compound, 2C3H7N6+·C4H4O62−·2H2O, in which the complete anion is generated by crystallographic twofold symmetry, there are O—H...O, N—H...O and N—H...N hydrogen-bonding interactions between neighbouring moieties, forming layers parallel to the bc plane. In addition, π–π contacts [centroid–centroid distance = 3.6541 (9 Å] between the six-membered rings of the melamine cations are observed.

  7. 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

  8. 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.

  9. 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).

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. COMPARATIVE STUDY OF NEW DRUG OF LONG ACTING METOPROLOL TARTRATE - EGILOK RETARD AND ORIGINAL DRUG OF METOPROLOL SUCCINATE – BETALOC ZOK IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    J. V. Lukina

    2015-12-01

    Full Text Available Aim. To study efficiency and safety of new drug of long acting metoprolol tartrate, “Egilok retard” (ER in patients with mild to moderate arterial hypertension (AH in comparison with the original drug of metoprolol succinat, “Betaloc ZOK” (BZ, possibility of reaching target blood pressure (BP level with treatment with each drug.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. Previous antihypertensive treatment had been canceled for all the patients 10-14 days before the study started. Each patient by turns was treated during 6 weeks with ER and BZ 50-100 mg daily. After cancellation of the previous antihypertensive therapy, BZ and ER were prescribed (according to the randomization table in dose 50 mg daily. Drugs were taken once per day. 29 patients completed therapy with the first drug of randomization, 25 patients – with the second. After 2 weeks efficiency of treatment was assessed by target BP level achievement (< 140/90 mmHg. If efficiency of beta-adrenoblocker (BB was not sufficient, the dose of the drug was doubled to 100 mg daily, if target level was reached – the dose remained unchanged. Treatment with the settled dose was held within next 4 weeks. After 6-week treatment with the first randomized drug antihypertensive therapy was canceled for 10-14 days depending on the BB dose. At each visit office BP and heart rate were assessed, EKG was registered. Side-effects were registered according to the self-control diary, questionnaire results, examination and EKG data.Results. After 6-week treatment with ER and BZ average level of systolic BP reduced by 15,7 and 15,2 mmHg, of diastolic BP – by 8,0 and 4,5 mmHg, heart rate – by 4,1 and 4,3 beat/min respectively. Differences between antihypertensive and heart rate lowering effect of the studied drugs were not significant. Target BP level with treatment with both drugs was reached in approximately

  18. COMPARATIVE STUDY OF NEW DRUG OF LONG ACTING METOPROLOL TARTRATE - EGILOK RETARD AND ORIGINAL DRUG OF METOPROLOL SUCCINATE – BETALOC ZOK IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    J. V. Lukina

    2005-01-01

    Full Text Available Aim. To study efficiency and safety of new drug of long acting metoprolol tartrate, “Egilok retard” (ER in patients with mild to moderate arterial hypertension (AH in comparison with the original drug of metoprolol succinat, “Betaloc ZOK” (BZ, possibility of reaching target blood pressure (BP level with treatment with each drug.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. Previous antihypertensive treatment had been canceled for all the patients 10-14 days before the study started. Each patient by turns was treated during 6 weeks with ER and BZ 50-100 mg daily. After cancellation of the previous antihypertensive therapy, BZ and ER were prescribed (according to the randomization table in dose 50 mg daily. Drugs were taken once per day. 29 patients completed therapy with the first drug of randomization, 25 patients – with the second. After 2 weeks efficiency of treatment was assessed by target BP level achievement (< 140/90 mmHg. If efficiency of beta-adrenoblocker (BB was not sufficient, the dose of the drug was doubled to 100 mg daily, if target level was reached – the dose remained unchanged. Treatment with the settled dose was held within next 4 weeks. After 6-week treatment with the first randomized drug antihypertensive therapy was canceled for 10-14 days depending on the BB dose. At each visit office BP and heart rate were assessed, EKG was registered. Side-effects were registered according to the self-control diary, questionnaire results, examination and EKG data.Results. After 6-week treatment with ER and BZ average level of systolic BP reduced by 15,7 and 15,2 mmHg, of diastolic BP – by 8,0 and 4,5 mmHg, heart rate – by 4,1 and 4,3 beat/min respectively. Differences between antihypertensive and heart rate lowering effect of the studied drugs were not significant. Target BP level with treatment with both drugs was reached in approximately

  19. Prescripción y vigilancia de la inmunoterapia sublingual con vacunas estandarizadas de ácaros domésticos en un servicio de alergología

    Directory of Open Access Journals (Sweden)

    Mirta Álvarez

    2012-12-01

    Full Text Available Las vacunas terapéuticas para la alergia, también llamadas inmunoterapia alergeno específica, consisten en la administración de dosis progresivamente crecientes del alergeno al cual el individuo está sensibilizado, con el objetivo de alcanzar tolerancia al mismo y disminuir la sintomatología clínica. Se realizó un estudio descriptivo, de corte transversal para determinar la seguridad de las vacunas de ácaros domésticos (VALERGEN, administradas mediante gotas por vía sublingual. Se verificaron sus eventos adversos en pacientes alérgicos, atendidos en el Departamento de Alergología del hospital universitario "Calixto García", que asistieron a cambios de vacunas en el mes de septiembre de 2010, así como la frecuencia de prescripción de vacunas alergénicas en el período enero-septiembre del mismo año. Se incluyeron 130 pacientes con tratamiento de inmunoterapia sublingual con VALERGEN, con una edad media de 19,6 años (rango 1-75; el 40,7% tenía 17 años o menos. El tipo de vacuna más empleada resultó ser la multialergénica (63,8%. El ácaro más empleado fue el Dermatophagoides pteronyssinus, seguido de Blomia tropicalis . El 71,55% de los casos se encontraban en fase de mantenimiento. Se reportaron cuatro eventos adversos (3,1% locales leves, que no requirieron tratamiento ni cambio de pauta de vacunación. Se comprobó que las vacunas sublinguales VALERGEN son seguras y bien toleradas en los pacientes alérgicos.

  20. Comparação entre nifedipina por via sublingual e clonidina por via venosa no controle de hipertensão arterial peri-operatória em cirurgias de catarata

    Directory of Open Access Journals (Sweden)

    Stocche Renato Mestriner

    2002-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Estudo recente mostra que a clonidina por via venosa apresenta-se eficaz e segura no tratamento de crises hipertensivas durante cirurgia de catarata. Este estudo visa comparar o uso de nifedipina, droga amplamente utilizada por via sublingual, e clonidina por via venosa no controle da hipertensão arterial em cirurgias de catarata. MÉTODO: Setenta e cinco pacientes submetidos à facectomia foram distribuídos de forma aleatória e encoberta em: Grupo A, que recebeu nifedipina e Grupos C2 e C3, que receberam, respectivamente, 2 e 3 µg.kg-1 de clonidina por via venosa. Todos os pacientes apresentavam hipertensão arterial (PAS > 170 mmHg ou PAD > 110 mmHg. As PAS, PAD e freqüência cardíaca (FC foram medidas e comparadas nos momentos: 0 (antes do tratamento e de 2 em 2 minutos até o final do procedimento. Os eventos adversos foram anotados. RESULTADOS: Após o tratamento ocorreram diminuições da PAS e PAD nos 3 grupos (p <0,001. Houve controle da pressão arterial (<160 mmHg em 32%, 64% e 72% dos pacientes nos grupos A, C2 e C3, respectivamente (p < 0,05. No grupo C3 ocorreu maior incidência de efeitos colaterais que nos grupos C2 e A (p < 0,05. CONCLUSÕES:A clonidina por via venosa é mais eficaz que a nifedipina, por via sublingual, no controle de crises hipertensivas no peri-operatório de cirurgias de catarata. Contudo, a dose de 3 µg.kg-1 pode estar relacionada a efeitos colaterais, devendo-se iniciar o tratamento com 2 µg.kg-1.

  1. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study.

    Science.gov (United States)

    Moore, Angela; Kempers, Steven; Murakawa, George; Weiss, Jonathan; Tauscher, Amanda; Swinyer, Leonard; Liu, Hong; Leoni, Matthew

    2014-01-01

    Once-daily topical brimonidine tartrate (BT) gel 0.5% was shown to be efficacious and safe for the treatment of erythema of rosacea in previous studies including a 4-week treatment phase. In the present 1-year study, we aimed to assess the long-term safety and efficacy of the treatment. Subjects with moderate to severe erythema of rosacea were instructed to apply topical BT gel 0.5% once daily for 12 months. Severity of erythema and adverse events (AEs) were evaluated. Approximately 345 subject years of exposure to BT gel 0.5% was achieved in the study. The incidence of AEs and AEs judged to be r