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Sample records for administration intranasal

  1. Absorption of clonazepam after intranasal and buccal administration.

    OpenAIRE

    Schols-Hendriks, M W; Lohman, J J; Janknegt, R; Korten, J J; Merkus, F W; Hooymans, P M

    1995-01-01

    Serum concentrations of clonazepam after intranasal, buccal and intravenous administration were compared in a cross-over study in seven healthy male volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.) was measured 17.5 min (median) (range 15-20 min) after intranasal administration. A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7 h (range 0.7-3.0 h). Aft...

  2. Intranasal oxycodone self-administration in non-dependent opioid abusers

    OpenAIRE

    Middleton, L.S.; Lofwall, M.R.; Nuzzo, P.A.; Siegel, A.; Walsh, S.L.

    2012-01-01

    Oxycodone, an opioid with known abuse liability, is misused by the intranasal route. Our objective was to develop a model of intranasal oxycodone self-administration useful for assessing the relative reinforcing effects of opioids and potential pharmacotherapies for opioid use disorders. Healthy, sporadic intranasal opioid abusers (n=8; 7 M, 1 F) completed this inpatient 2.5-week, randomized, double blind, placebo-controlled, crossover study. Each intranasal oxycodone dose (0, 14 & 28 mg) was...

  3. Distribution of nimodipine in brain following intranasal administration in rats

    Institute of Scientific and Technical Information of China (English)

    Qi-zhi ZHANG; Xin-guo JIANG; Chun-hua WU

    2004-01-01

    AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed by HPLC. RESULTS:Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.26 and 1.39 fold compared with the iv route, respectively.The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01). CONCLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

  4. Postprandial Administration of Intranasal Insulin Intensifies Satiety and Reduces Intake of Palatable Snacks in Women

    OpenAIRE

    Hallschmid, Manfred; Higgs, Suzanne; Thienel, Matthias; Ott, Volker; Lehnert, Hendrik

    2012-01-01

    The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookie...

  5. Targeting glioblastoma via intranasal administration of Ff bacteriophages

    Science.gov (United States)

    Dor-On, Eyal; Solomon, Beka

    2015-01-01

    Bacteriophages (phages) are ubiquitous viruses that control the growth and diversity of bacteria. Although they have no tropism to mammalian cells, accumulated evidence suggests that phages are not neutral to the mammalian macro-host and can promote immunomodulatory and anti-tumorigenic activities. Here we demonstrate that Ff phages that do not display any proteins or peptides could inhibit the growth of subcutaneous glioblastoma tumors in mice and that this activity is mediated in part by lipopolysaccharide molecules attached to their virion. Using the intranasal route, a non-invasive approach to deliver therapeutics directly to the CNS, we further show that phages rapidly accumulate in the brains of mice and could attenuate progression of orthotopic glioblastoma. Taken together, this study provides new insight into phages non-bacterial activities and demonstrates the feasibility of delivering Ff phages intranasally to treat brain malignancies. PMID:26074908

  6. Targeting glioblastoma via intranasal administration of Ff bacteriophages

    Directory of Open Access Journals (Sweden)

    Eyal eDor-On

    2015-05-01

    Full Text Available Bacteriophages (phages are ubiquitous viruses that control the growth and diversity of bacteria. Although they have no tropism to mammalian cells, accumulated evidence suggests that phages are not neutral to the mammalian macro-host and can promote immunomodulatory and anti-tumorigenic activities. Here we demonstrate that Ff phages that do not display any proteins or peptides could inhibit the growth of subcutaneous glioblastoma tumors in mice and that this activity is mediated in part by lipopolysaccharide molecules attached to their virion. Using the intranasal route, a non-invasive approach to deliver therapeutics directly to the CNS, we further show that phages rapidly accumulate in the brains of mice and could attenuate progression of orthotopic glioblastoma. Taken together, this study provides new insight into phages non-bacterial activities and demonstrates the feasibility of delivering Ff phages intranasally to treat brain malignancies.

  7. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs

    NARCIS (Netherlands)

    Camerlink, Irene; Reimert, Inonge; Bolhuis, Liesbeth

    2016-01-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for posi

  8. Elevated salivary levels of oxytocin persist more than seven hours after intranasal administration

    Directory of Open Access Journals (Sweden)

    Marinus H. Van IJzendoorn

    2012-12-01

    Full Text Available We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 IU or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 AM of 16 IU (n = 18 or 24 IU (n = 10 of oxytocin, or a placebo (n = 18, and each hour after administration, for 7h in total.Oxytocin levels did not differ among conditions before use of the nasal spray. Salivary oxytocin levels in the placebo group showed high stability across the day. After oxytocin administration oxytocin levels markedly increased, they peaked around 1h after administration, and were still significantly elevated 7h after administration. The amount of oxytocin (16 IU or 24 IU did not make a difference for oxytocin levels. The increase of oxytocin levels for at least 7h shows how effective intranasal administration of oxytocin is. Our findings may raise ethical questions about potentially persisting behavioral effects after participants have left the lab setting. More research into the long-term neurological and behavioral effects of sniffs of oxytocin is urgently needed.

  9. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    Science.gov (United States)

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels.

  10. Midazolam premedication in children: a pilot study comparing intramuscular and intranasal administration.

    Science.gov (United States)

    Lam, Christy; Udin, Richard D; Malamed, Stanley F; Good, David L; Forrest, Jane L

    2005-01-01

    The purpose of this study was to compare the effectiveness of intramuscular and intranasal midazolam used as a premedication before intravenous conscious sedation. Twenty-three children who were scheduled to receive dental treatment under intravenous sedation participated. The patients ranged in age from 2 to 9 years (mean age, 5.13 years) and were randomly assigned to receive a dose of 0.2 mg/kg of midazolam premedication via either intramuscular or intranasal administration. All patients received 50% nitrous oxide and 50% oxygen inhalation sedation and local anesthetic (0.2 mL of 4% prilocaine hydrochloride) before venipuncture. The sedation level, movement, and crying were evaluated at the following time points: 10 minutes after drug administration and at the times of parental separation, passive papoose board restraint, nitrous oxide nasal hood placement, local anesthetic administration, and initial venipuncture attempt. Mean ratings for the behavioral parameters of sedation level, degree of movement, and degree of crying were consistently higher but not significant in the intramuscular midazolam group at all 6 assessment points. Intramuscular midazolam was found to be statistically more effective in providing a better sedation level and less movement at the time of venipuncture than intranasal administration. Our findings indicate a tendency for intramuscular midazolam to be more effective as a premedication before intravenous sedation.

  11. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup;

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis......Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D) in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas...... was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4+Foxp3+ T cells and even more significant induction of γδ T cells in mucosal...

  12. Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

    Science.gov (United States)

    Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

    2015-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

  13. Intranasal administration of oxytocin increases compassion toward women.

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    Palgi, Sharon; Klein, Ehud; Shamay-Tsoory, Simone G

    2015-03-01

    It has been suggested that the degree of compassion-the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers' views regarding the target's vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in 'tend-and-befriend' behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants' responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals.

  14. Intranasal administration of oxytocin increases compassion toward women.

    Science.gov (United States)

    Palgi, Sharon; Klein, Ehud; Shamay-Tsoory, Simone G

    2015-03-01

    It has been suggested that the degree of compassion-the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers' views regarding the target's vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in 'tend-and-befriend' behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants' responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals. PMID:24711542

  15. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs.

    Science.gov (United States)

    Camerlink, Irene; Reimert, Inonge; Bolhuis, J Elizabeth

    2016-09-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for positive indicators of animal welfare. We investigated whether oxytocin alters social nosing and whether this is specific to nose-body or nose-nose contact. Sixty-four focal female pigs of 13weeks of age (out of 16 groups) were given oxytocin (24IU dose) and saline (placebo) intranasally once on two consecutive days. The frequency of nose-to-nose contact and nose-to-body contact was recorded upon pigs' return in the home pen after being for 10min located in a separate area near pen mates undergoing a positive or negative event or not. The effect of intranasal oxytocin depended on the social context in which pigs were studied. Control pigs, which were not exposed to positively or negatively aroused pen mates, gave and received less nose-nose contact after oxytocin administration than after saline administration. Pigs exposed to positively aroused pen mates also tended to give less nose contact when given oxytocin compared to saline, whereas pigs exposed to negatively aroused pen mates and administered oxytocin tended to receive more nose contact. Nose-body contact was lowest in groups of negative social context, suggesting an effect of emotional state on social nosing. In contrast to nose-nose contact, nose-body contact was unaffected by oxytocin treatment. The relationship between social nosing and oxytocin merits further research.

  16. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs.

    Science.gov (United States)

    Camerlink, Irene; Reimert, Inonge; Bolhuis, J Elizabeth

    2016-09-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for positive indicators of animal welfare. We investigated whether oxytocin alters social nosing and whether this is specific to nose-body or nose-nose contact. Sixty-four focal female pigs of 13weeks of age (out of 16 groups) were given oxytocin (24IU dose) and saline (placebo) intranasally once on two consecutive days. The frequency of nose-to-nose contact and nose-to-body contact was recorded upon pigs' return in the home pen after being for 10min located in a separate area near pen mates undergoing a positive or negative event or not. The effect of intranasal oxytocin depended on the social context in which pigs were studied. Control pigs, which were not exposed to positively or negatively aroused pen mates, gave and received less nose-nose contact after oxytocin administration than after saline administration. Pigs exposed to positively aroused pen mates also tended to give less nose contact when given oxytocin compared to saline, whereas pigs exposed to negatively aroused pen mates and administered oxytocin tended to receive more nose contact. Nose-body contact was lowest in groups of negative social context, suggesting an effect of emotional state on social nosing. In contrast to nose-nose contact, nose-body contact was unaffected by oxytocin treatment. The relationship between social nosing and oxytocin merits further research. PMID:27143253

  17. Preparation of ESAT-6 Nanoparticles and Evaluation of Humoral Immunity after Intranasal Administration

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    H Najminezhad

    2013-01-01

    Full Text Available Introduction: Among several tuberculosis vaccine candidates for replacement of BCG, ESAT-6 protein has a special role. Since mycobacterium tuberculosis infection most often attacks the lungs, intranasal rout can be regarded as appropriate methods for tuberculosis vaccines and drug delivery. One of the appropriate systems for intranasal vaccine delivery is using biodegradable nanoparticles. Among biodegradable polymers, chitosan polymer has great features to increase the response of immunity system. This study aimed to investigate the specific humoral immune response of mice model after encapsulation of recombinant ESAT-6 antigen in chitosan nanoparticles. Methods: The chitosan nanoparticles containing ESAT-6 antigen were synthesized by ionic gelation. Nanoparticle properties including morphology, particle size, zeta potential, encapsulation rates, and protein release were measured in vitro. The immunization was performed through the nose for 3 times on days 0 and 14 and 28. 2 weeks after last administration, blood samples were collected and specific IgG titers were measured by indirect ELISA. Results: The nanoparticles synthesized had appropriate properties. The mean size of resulting nanoparticles was 242.8 nm by excellent antigen loading capacity (95.23 %. The vitro release of antigen from nanoparticles after 200 hours was detected as 67.5%. The Level of IgG antibody showed significant increase in the group that had received chitosan nanoparticles containing ESAT-6 compared with other groups. Conclusion: ESAT-6 protein was encapsulated in chitosan nanoparticles successfully. Administration of chitosan nanoparticles can be a suitable method for administration of humoral immunity antigens of Mycobacterium tuberculosis through intranasal rout.

  18. Prehospital Medication Administration: A Randomised Study Comparing Intranasal and Intravenous Routes

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    Cian McDermott

    2012-01-01

    Full Text Available Introduction. Opioid overdose is an ever-increasing problem globally. Recent studies have demonstrated that intranasal (IN naloxone is a safe and effective alternative to traditional routes of naloxone administration for reversal of opioid overdose. Aims. This randomised controlled trial aimed to compare the time taken to deliver intranasal medication with that of intravenous (IV medication by advanced paramedic trainees. Methods. 18 advanced paramedic trainees administered either an IN or IV medication to a mannequin model in a classroom-based setting. The time taken for medication delivery was compared. End-user satisfaction was assessed using a 5-point questionnaire regarding ease of use and safety for both routes. Results. The mean time taken for the IN and IV group was 87.1 seconds and 178.2 seconds respectively. The difference in mean time taken was 91.1 seconds (95% confidence interval 55.2 seconds to 126.9 seconds, P≤0.0001. 89% of advanced paramedic trainees reported that the IN route was easier and safer to use than the IV route. Conclusion. This study demonstrates that, amongst advanced paramedic trainees, the IN route of medication administration is significantly faster, better accepted and perceived to be safer than using the IV route. Thus, IN medication administration could be considered more frequently when administering emergency medications in a pre-hospital setting.

  19. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice.

    Directory of Open Access Journals (Sweden)

    David P Funda

    Full Text Available Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n. administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4(+Foxp3(+ T cells and even more significant induction of γδ T cells in mucosal, but not in non-mucosal lymphoid compartments. This prevention strategy was characterized by an increased proportion of IL-10 and a decreased proportion of IL-2, IL-4 and IFN-γ-positive CD4(+Foxp3(+ T cells, and IFN-γ-positive γδ T cells, preferentially in mucosal lymphoid organs. In conclusion, i.n. vaccination with gliadin, an environmental antigen with possible etiological influence in T1D, may represent a novel, safer strategy for prevention or even early cure of T1D.

  20. Intranasal administration of nanostructured lipid carriers containing CNS acting drug: pharmacodynamic studies and estimation in blood and brain.

    Science.gov (United States)

    Alam, M Intakhab; Baboota, Sanjula; Ahuja, Alka; Ali, Mushir; Ali, Javed; Sahni, Jasjeet K

    2012-09-01

    The present study was aimed to investigate and compare the efficacy of duloxetine (DLX) loaded nanostructured lipid carriers (NLC) with DLX solution pharmacodynamically following intranasal administration. The study was further conducted to estimate DLX concentration in brain and blood. DLX was administered to albino Wistar rats either intranasally or orally in solution form (DLX solution) or encapsulated in NLC (DLX-NLC). These were evaluated in-vivo for pharmacodynamic studies for depression by forced swimming test and locomotor activity test. Intranasal DLX-NLC treatment exhibited improved behavioural analysis results (swimming, climbing, and immobility) than the DLX solution after 24 h of study. Furthermore, DLX-NLC significantly increased the total swimming and climbing time when compared with control and significantly reduced the immobility period. The intranasal DLX-NLC demonstrated improved locomotor activity when compared with DLX solution. Amount of DLX was quantified in blood and brain after the forced swimming test. The intranasal DLX-NLC demonstrated higher concentration in brain compared with DLX solution. Thus, intranasal DLX-NLC was found to be a promising formulation for the treatment of depression.

  1. Comparison of Preanesthetic Sedation after Intranasal Administration of Fentanyle, Ketamin and Midazolam

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    F Javaherforoosh

    2006-07-01

    Full Text Available Introduction & Objective: Induction of anesthesia in children can be a challenge for anesthetist. A stormy induction may increase the personality & behavioral changes. Therefore, it is desirable that they enter the operating room sedated. Many drugs are used for preanesthetic medication and there are many routes for administration. One route of administration is nasal mucous. In this study we compared the effect and side effect of three drugs (midazolam, ketamin and fentanyle after intra nasal administration. Materials & Methods: This is a double blind clinical trial. In this study we selected 60 patients (20 patients for every group A, B or C. We used 3 mg/kg ketamin or 3µg/kg fentanyle or 0.3 mg/kg midazolam by intranasal spray. After administration and in 5, 10 and 15 minutes, we observed the SPO2, PR and RR. After 15 min’s we separated children from parents and brought them to the operating room and controlled the acceptance of separation, depth of sedation with Ramsay score, acceptance of mask and tolerance of IV canulation. The data were then analyzed using K2 and kruskal-wallis test. Results: In our study we found that in SPO2 fentanyle had the highest rate of reduction even though none of the children had SPO2 lower than 90%. There were no differences between drugs in RR. In fentanyle group, we had the lowest rate and in ketamin group the highest rate. Midazolam had the medium rate. The rate of sedation for acceptance of separation from parents had no difference between the groups and all drugs with this dosage were effective for this aim. However, in Ramsay score, acceptance of mask and tolerance of IV canulation, the midazolam was more effective than the others. Conclusion: Intranasal administration of midazolam is a safe route for sedation in children in the pre-anesthetic time.

  2. Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Kreutzmann, Judith C.; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jaap M.

    2015-01-01

    Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and pro

  3. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A;

    1995-01-01

    quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  4. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model

    Directory of Open Access Journals (Sweden)

    Sharareh Eskandari

    2011-02-01

    Full Text Available Sharareh Eskandari1, Jaleh Varshosaz1, Mohsen Minaiyan2, Majid Tabbakhian11Department of Pharmaceutics, 2Department of Pharmacology, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the brain for a prolonged period. The objective of this study was delivery of valproic acid (VPA to the brain by intranasal route. For this purpose, nanostructured lipid carriers (NLCs were prepared by solvent diffusion method followed by ultrasonication and characterized for size, zeta potential, drug-loading percentage, and release. Six groups of rats each containing six animals received drug-loaded NLCs intraperitoneally (IP or intranasally. Brain responses were then examined by using maximal electroshock (MES. The hind limb tonic extension:flexion inhibition ratio was measured at 15-, 30-, 60-, 90-, and 120-minute intervals. The drug concentration was also measured in plasma and brain at the most protective point using gas chromatography method. The particle size of NLCs was 154 ± 16 nm with drug-loading percentage of 47% ± 0.8% and drug release of 75% ± 1.9% after 21 days. In vivo results showed that there was a significant difference between protective effects of NLCs of VPA and control group 15, 30, 60, and 90 minutes after treatment via intranasal route (P < 0.05. Similar protective effect was observed in rats treated with NLCs of VPA in intranasal route and positive control in IP route (P > 0.05. Results of drug determination in brain and plasma showed that brain:plasma concentration ratio was much higher after intranasal administration of NLCs of VPA than the positive control group (IP route. In conclusion, intranasal administration of NLCs of VPA provided a better protection

  5. Evidence for Status Epilepticus and Pro-Inflammatory Changes after Intranasal Kainic Acid Administration in Mice.

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    Mounira Sabilallah

    Full Text Available Kainic acid (KA is routinely used to elicit status epilepticus (SE and epileptogenesis. Among the available KA administration protocols, intranasal instillation (IN remains understudied. Dosages of KA were instilled IN in mice. Racine Scale and Video-EEG were used to assess and quantify SE onset. Time spent in SE and spike activity was quantified for each animal and confirmed by power spectrum analysis. Immunohistochemistry and qPCR were performed to define brain inflammation occurring after SE, including activated microglial phenotypes. Long term video-EEG recording was also performed. Titration of IN KA showed that a dose of 30 mg/kg was associated with low mortality while eliciting SE. IN KA provoked at least one behavioral and electrographic SE in the majority of the mice (>90%. Behavioral and EEG SE were accompanied by a rapid and persistent microglial-astrocytic cell activation and hippocampal neurodegeneration. Specifically, microglial modifications involved both pro- (M1 and anti-inflammatory (M2 genes. Our initial long-term video-EEG exploration conducted using a small cohort of mice indicated the appearance of spike activity or SE. Our study demonstrated that induction of SE is attainable using IN KA in mice. Typical pro-inflammatory brain changes were observed in this model after SE, supporting disease pathophysiology. Our results are in favor of the further development of IN KA as a means to study seizure disorders. A possibility for tailoring this model to drug testing or to study mechanisms of disease is offered.

  6. Intranasal Administration of Chitosan Against Influenza A (H7N9) Virus Infection in a Mouse Model

    Science.gov (United States)

    Zheng, Mei; Qu, Di; Wang, Haiming; Sun, Zhiping; Liu, Xueying; Chen, Jianjun; Li, Changgui; Li, Xuguang; Chen, Ze

    2016-01-01

    Influenza virus evolves constantly in an unpredictable fashion, making it necessary to vaccinate people annually for effective prevention and control of influenza. In general, however, during the first wave of an influenza outbreak caused by a newly emerging virus strain, influenza morbidity and mortality have been observed to rise sharply due to the lack of a matching vaccine. This necessitates the exploration of novel intervention approaches, particularly those prophylactic or therapeutic agents that have a broad range of antiviral activities and are also proven to be non-toxic. Here, we reported that stimulation of the innate immune system by intranasal administration of chitosan as a single agent was sufficient to completely protect BALB/c mice from lethal infection by H7N9 virus, a newly emerged viral strain that is highly pathogenic to humans. Remarkably, animals could still be protected against lethal challenge by H7N9 (10×LD50), even ten days after the intranasal chitosan administration. The significantly enhanced infiltration of leukocytes in the bronchoalveolar lavage and elevated levels of proinflammatory cytokines in the bronchia/lung tissues revealed the potent activation of mucosal immune responses by intranasally delivered chitosan. We also observed that chitosan can protect mice from three other virus strains. The marked breadth and magnitude of protection against diverse viral strains makes chitosan an attractive candidate as a universal anti-influenza agent. PMID:27353250

  7. Enhanced mucosal and systemic immune response with squalane oil-containing multiple emulsions upon intranasal and oral administration in mice.

    Science.gov (United States)

    Shahiwala, Aliasgar; Amiji, Mansoor M

    2008-05-01

    The objective of this study was to develop and evaluate squalane oil-containing water-in-oil-in-water (W/O/W) multiple emulsion for mucosal administration of ovalbumin (OVA) as a model candidate vaccine in BALB/c mice. Control and optimized OVA-containing W/O/W emulsion (OVA-Emul) and chitosan-modified W/O/W emulsion (OVA-Emul-Chi) formulations were administered intranasally and orally at an OVA dose of 100 mug. The mucosal and systemic immune responses were evaluated after the first and second immunization. The OVA-Emul formulations resulted in higher immunoglobulin-G (IgG) and immunoglobulin-A (IgA) responses as compared with aqueous solution. In addition, significant IgG and IgA responses were observed after the second immunization dose using the emulsions with both routes of administration. Intranasal vaccination was more effective in generating the systemic OVA-specific IgG response than the mucosal OVA-specific IgA response. Oral immunizations, on the other hand, showed a much higher systemic IgG and mucosal IgA responses as compared with the nasally treated groups. The results of this study show that squalane oil-containing W/O/W multiple emulsion formulations can significantly enhance the local and systemic immune responses, especially after oral administration, and may be adopted as a better alternative in mucosal delivery of prophylactic and therapeutic vaccines.

  8. Intranasal insulin therapy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  9. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    Energy Technology Data Exchange (ETDEWEB)

    Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa, E-mail: etyszkiewicz@wum.edu.pl

    2012-11-15

    The effect of intranasal manganese chloride (MnCl{sub 2}·4H{sub 2}O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl{sub 2}·4H{sub 2}O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

  10. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    International Nuclear Information System (INIS)

    The effect of intranasal manganese chloride (MnCl2·4H2O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl2·4H2O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

  11. Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI mouse model. In this study, we investigated the potential of human MSCs (hMSCs to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our knowledge to the clinic. We determined the neuroregenerative potential of hMSCs in vitro and in vivo by intranasal administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups. 1×10(6 or 2×10(6 hMSCs were administered intranasally 10 d post-HI. Motor behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of hMSCs to induce differentiation of mouse neural stem cell (mNSC was determined using a transwell co-culture differentiation assay. To determine which chemotactic factors may play a role in mediating migration of MSCs to the lesion, we performed a PCR array on 84 chemotactic factors 10 days following sham-operation, and at 10 and 17 days post-HI. Our results show that 2×10(6 hMSCs decrease lesion volume, improve motor behavior, and reduce scar formation and microglia activity. Moreover, we demonstrate that the differentiation assay reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs to differentiate into neurons in vitro. We also provide evidence that the chemotactic factor CXCL10 may play an important role in hMSC migration to the lesion site. This is suggested by our finding that CXCL10 is significantly upregulated at 10 days following HI, but not at 17 days after HI, a time when MSCs no longer reach the lesion when given intranasally. The results described in this work also tempt us to contemplate hMSCs not only as a potential treatment option for neonatal encephalopathy, but also for a plethora of degenerative and traumatic injuries of the nervous system.

  12. Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhiwu Sun

    2015-02-01

    Full Text Available Respiratory syncytial virus (RSV is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP of RSV infection in children at high risk. We found that maleic anhydride (ML-modified human serum albumin (HSA, designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.

  13. Intravenous or intranasal administration of gliadin is able to down-regulate the specific immune response in mice.

    Science.gov (United States)

    Rossi, M; Maurano, F; Caputo, N; Auricchio, S; Sette, A; Capparelli, R; Troncone, R

    1999-08-01

    The mucosal lesion in coeliac disease (CD) represents an immunologically mediated injury triggered by gliadin and is restricted by a particular assortment of major histocompatibility complex (MHC) class II genes. Therefore, immunomodulatory strategies to tolerize gliadin-specific, class II-restricted T-cell responses could represent an alternative to current treatments of CD, which are based on a gluten-free diet. In this study, BALB/c mice derived from a gluten-free diet colony were tolerized by either intranasal (i.n.) or intravenous (i.v.) administration of single or multiple doses of gliadin. While a single dose failed to induce tolerance, a significant decrease in gliadin-specific T-cell proliferation was detected (P strategies for CD.

  14. Intranasal administration as a route for drug delivery to the brain: evidence for a unique pathway for albumin.

    Science.gov (United States)

    Falcone, Joseph A; Salameh, Therese S; Yi, Xiang; Cordy, Benjamin J; Mortell, William G; Kabanov, Alexander V; Banks, William A

    2014-10-01

    A variety of compounds will distribute into the brain when placed at the cribriform plate by intranasal (i.n.) administration. In this study, we investigated the ability of albumin, a protein that can act as a drug carrier but is excluded from brain by the blood-brain barrier, to distribute into the brain after i.n. administration. We labeled bovine serum albumin with [(125)I] ([(125)I]Alb) and studied its uptake into 11 brain regions and its entry into the blood from 5 minutes to 6 hours after i.n. administration. [(125)I]Alb was present throughout the brain at 5 minutes. Several regions showed distinct peaks in uptake that ranged from 5 minutes (parietal cortex) to 60 minutes (midbrain). About 2-4% of the i.n. [(125)I]Alb entered the bloodstream. The highest levels occurred in the olfactory bulb and striatum. Distribution was dose-dependent, with less taken up by whole brain, cortex, and blood at the higher dose of albumin. Uptake was selectively increased into the olfactory bulb and cortex by the fluid-phase stimulator PMA (phorbol 12-myristate 13-acetate), but inhibitors to receptor-mediated transcytosis, caveolae, and phosphoinositide 3-kinase were without effect. Albumin altered the distribution of radioactive leptin given by i.n. administration, decreasing uptake into the blood and by the cerebellum and increasing uptake by the hypothalamus. We conclude that [(125)I]Alb administered i.n. reaches all parts of the brain through a dose-dependent mechanism that may involve fluid-phase transcytosis and, as illustrated by leptin, can affect the delivery of other substances to the brain after their i.n. administration.

  15. Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens

    NARCIS (Netherlands)

    C.B.M. Maassen (Kitty); J.D. Laman (Jon); C. van Holten-Neelen; L. Hoogteijling (L.); L. Groenewegen (Lizet); L. Visser (Lizette); M.M. Schellekens (M.); W.G. Boersma (Wim); H.J.H.M. Claassen (Eric)

    2003-01-01

    textabstractOral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we

  16. Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing meyelin antigens

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, van J.C.P.A.; Groenewegen, L.; Hoogteijling, L.; Visser, L.; Boersma, W.J.A.

    2003-01-01

    Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetica

  17. Intranasal administration of carbamazepine to mice: a direct delivery pathway for brain targeting

    OpenAIRE

    Serralheiro, Ana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar

    2014-01-01

    The currently available antiepileptic drugs are typically administered via oral or intravenous (IV) routes which commonly exhibit high systemic distribution into non-targeted tissues, leading to peripheral adverse effects and limited brain uptake. In order to improve the efficacy and tolerability of the antiepileptic drug therapy, alternative administration strategies have been investigated. The purpose of the present study was to assess the pharmacokinetics of carbamazepine administered via ...

  18. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  19. Intranasal administration of milnacipran in rats: evaluation of the transport of drugs to the systemic circulation and central nervous system and the pharmacological effect.

    Science.gov (United States)

    Uchida, Masaki; Katoh, Takuya; Mori, Mutsuhiro; Maeno, Takuya; Ohtake, Kazuo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

    2011-01-01

    Recently, transnasal drug delivery has attracted a great deal of attention as an administration route to deliver drugs directly to the central nervous systems (CNS) and drug targeting of the CNS is expected to increase. In the present study, we investigated the possibility of using a transnasal delivery system for milnacipran, a serotonin-noradrenaline reuptake inhibitor (SNRI), by evaluating the transport to the systemic circulation and cerebrospinal fluid (CSF) and the pharmacological effect after intranasal (i.n.) administration. Moreover, the effect of chitosan as a bioadhesive material on the transport to the systemic circulation and CSF and the pharmacological effect after i.n. administration were evaluated. As a result, i.n. administration of milnacipran was found to produce a higher direct delivery to the CNS as well as to the systemic circulation, suggesting that this is a promising route of administration and an alternative to peroral (p.o.) administration. Furthermore, the i.n. co-administration with chitosan led to increased plasma and CSF concentrations and an enhanced pharmacological effect, evaluated by means of the forced swimming test. The results suggested that chitosan produced a long residence time of milnacipran in the nasal cavity due to its bioadhesive effect, leading to the enhanced transport of milnacipran from the systemic circulation to the CNS via the blood-brain barrier by an increase in systemic absorption as well as direct transport to the CNS, resulting in a higher antidepressant effect compared to that with p.o. administration.

  20. ADMINISTRACIÓN DE INSULINA POR VÍA INTRANASAL Y MEMORIA DECLARATIVA: REVISIÓN SISTEMÁTICA DE LA LITERATURA Intranasal insulin administration and declarative memory: A systematic review

    Directory of Open Access Journals (Sweden)

    Andrés Jagua Gualdrón

    2008-12-01

    Full Text Available Antecedentes. La insulina participa de los procesos de formación de la memoria y los defectos en su señalización podrían estar relacionados con el déficit cognitivo y las enfermedades neurode-generativas como la enfermedad de Alzheimer. Objetivo. Evaluar la relación entre la administración de la insulina por vía intranasal y la memoria declarativa en estudios en humanos. Material y métodos. Se realizó una búsqueda intensiva y sistemática de estudios publicados entre enero de 1997 y diciembre del 2008 a través de las bases de datos MEDLINE, Cochrane, DynaMed y LILACS. Los estudios fueron sometidos a dos pruebas de calidad metodológica, se les realizó un análisis crítico y se aplicó estadística básica. Resultados. Se hallaron cinco artículos que incluían 252 personas. De ellos 143 tenían diagnóstico probable de la enfermedad de Alzheimer o alteración cognitiva leve. Los estudios reportan mejoría en las tareas de la memoria a corto y largo plazo en los grupos que recibieron la insulina comparados con quienes recibieron el placebo. Conclusión. Los estudios son pocos y difíciles de comparar. Sin embargo tras este análisis puede sugerirse que la insulina actúa durante la formación de la memoria declarativa y podría emplearse en el tratamiento de los trastornos de la memoria.Background. Insulin acts in memory formation and its signal impairment can be related with mild cognitive impairment and neurodegenerative diseases like Alzheimer's disease. Objective. To evaluate the relationship between intranasal insulin administration and declarative memory in studies with human. Materials and methods. A systematic search of studies published from January 1997 to december 2008 through electronic databases MEDLINE, DynaMed, Cochrane and LIlACS. Articles were evaluated with two tests for methodological validity and a basic statistical analysis was performed. Results. We find five articles that include 252 persons. 143 have

  1. Serum and mucosal immunologic responses in children following the administration of a new inactivated intranasal anti-influenza vaccine.

    Science.gov (United States)

    Greenbaum, E; Furst, A; Kiderman, A; Stewart, B; Levy, R; Schlesinger, M; Morag, A; Zakay-Rones, Z

    2001-09-01

    Children are at considerable risk for influenza infection and may constitute the main vector for transmitting the virus to adults in the community. At present, the use of available vaccines in children is limited mainly because of a fear of side effects from the injection. Intranasal immunization was assessed as a painless, side effect-free method of facilitating the enrollment of children in vaccination programs. One intranasal dose of a trivalent inactive whole virus vaccine containing 20 microg of the three recommended seasonal viral strains was administered to 28 children recruited over two separate winter periods (1997/1998 and 1998/1999). No adverse effects were recorded. Serum IgG responses were determined by the hemagglutination inhibition (HI) method and nasal IgA responses by enzyme-linked immunosorbent assay (ELISA). In both study period seasons, 77.7%-94.4% of children were found to be immune. There was a 3.7 x and 4.7 x increase in geometric mean titer (GMT) for A/H3N2 strains, 1.9 x and 3.9 x for A/H1N1 strains, and a 3.2 x and 1.7 x for B strains in 1997/1998 and 1998/1999, respectively. The increase in GMT, as well as fourfold increases in titer level, was higher when calculated among the nonimmune children prior to vaccination. Of these, 50%-87.5% became immune following immunization. Local antibody response to the three viral strains was detected in 50%-55% of the immunized children. Also, 83.3%, 73.3%, and 61.1% of the vaccinees exhibited a mucosal and/or serum antibody response to the A/Beijing, A/Sydney, and B/Harbin strains, respectively. This mucosal response may forestall influenza development in its early stages, thereby contributing significantly to the reduction of influenza spread in the community.

  2. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  3. Men perform comparably to women in a perspective taking task after administration of intranasal oxytocin but not after placebo.

    Directory of Open Access Journals (Sweden)

    Angeliki eTheodoridou

    2013-05-01

    Full Text Available Oxytocin (OT is thought to play an important role in human interpersonal information processing and behavior. By inference, OT should facilitate empathic responding, i.e. the ability to feel for others and to take their perspective. In two independent double-blind, placebo-controlled between-subjects studies, we assessed the effect of intranasally administered OT on affective empathy and perspective taking, whilst also examining potential sex differences (e.g., women being more empathic than men. In study 1, we provided 96 participants (48 men with an empathy scenario and recorded self reports of empathic reactions to the scenario, while in study 2, a sample of 120 individuals (60 men performed a computerized implicit perspective taking task. Whilst results from Study 1 showed no influence of OT on affective empathy, we found in Study 2 that OT exerted an effect on perspective taking ability in men. More specifically, men responded faster than women in the placebo group but they responded as slowly as women in the OT group. We conjecture that men in the OT group adopted a social perspective taking strategy, such as did women in both groups, but not men in the placebo group. On the basis of results across both studies, we suggest that self-report measures (such as used in Study 1 might be less sensitive to OT effects than more implicit measures of empathy such as that used in Study 2. If these assumptions are confirmed, one could infer that OT effects on empathic responses are more pronounced in men than women, and that any such effect is best studied using more implicit measures of empathy rather than explicit self-report measures.

  4. The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: a meta-analysis.

    Science.gov (United States)

    Shahrestani, Sara; Kemp, Andrew H; Guastella, Adam J

    2013-09-01

    Many studies have highlighted the potential of oxytocin (OT) to enhance facial affect recognition in healthy humans. However, inconsistencies have emerged with regard to the influence of OT on the recognition of specific emotional expressions (happy, angry, fear, surprise, disgust, and sadness). In this study, we conducted a meta-analysis of seven studies comprising 381 research participants (71 females) examining responses to the basic emotion types to assess whether OT enhances the recognition of emotion from human faces and whether this was influenced by the emotion expression and exposure time of the face. Results showed that intranasal OT administration enhances emotion recognition of faces overall, with a Hedges g effect size of 0.29. When analysis was restricted to facial expression types, significant effects of OT on recognition accuracy were specifically found for the recognition of happy and fear faces. We also found that effect sizes increased to moderate when exposure time of the photograph was restricted to early phase recognition (recognition for fear faces (> 300 ms). The results of the meta-analysis further suggest that OT has potential as a treatment to improve the recognition of emotion in faces, allowing individuals to improve their insight into the intentions, desires, and mental states of others.

  5. CpG Immunotherapy in Chenopodium album sensitized mice: The comparison of IFN-gamma, IL-10 and IgE responses in intranasal and subcutaneous administrations

    Directory of Open Access Journals (Sweden)

    Moradi Maziar

    2008-09-01

    Full Text Available Abstract Background Mucosal-based immunotherapy has been already used as an alternative form of allergen delivery. In asthma, the poor success rate of immune modulation could be a consequence of inadequate immune modulation in the airways. Previously, we have found that subcutaneous (S.C co-administration of a homemade allergenic extract from Chenopodium album (Ch.a pollen and Guanine-Cytosine containing deoxynucleotides (CpG-ODNs is effective to prevent the inflammatory responses in mouse. In this study we used CpG/Ch.a for immunotherapy of Ch.a-induced asthma and compared the intranasal (I.N and S.C routes of administration concerning IFN-γ, IL-10 and total IgE responses. Methods Ch.a sensitized mice were treated intranasaly or subcutaneously using CpG and Ch.a. extract. IFN-γ, IL-10 and total IgE were measured in supernatant culture of splenocytes and bronchoalveolor lavage (BAL fluids by ELISA. Student's t test was used in the analysis of the results obtained from the test and control mice. Results We found that I.N administration of CpG/Ch.a in sensitized mice significantly increased the production of systemic and mucosal IFN-γ and IL-10 compared to phosphate buffered saline (PBS, Ch.a alone and control ODNs treated sensitized mice (P ≤ 0.001. On the other hand, S.C. route induced the systemic and mucosal IFN-γ in the lower levels than in I.N one, and failed to increase systemic IL-10 induction (P = 0.06. Total serum IgE in CpG/Ch.a treated mice in both routes showed significant decreases compared to three control groups (P ≤ 0.01. The amounts of IgE in BAL fluids were not measurable in all groups. Conclusion According to the results of this experiment we concluded that immunotherapy via the I.N co-administration of CpG/Ch.a in comparison with S.C route is more effective to stimulate the mucosal and regulatory responses in Ch.a induced asthma.

  6. Intranasal administration of recombinant TRAIL down-regulates CXCL-1/KC in an ovalbumin-induced airway inflammation murine model.

    Directory of Open Access Journals (Sweden)

    Veronica Tisato

    Full Text Available Ovalbumin (OVA-sensitized BALB/c mice were i.n. instilled with recombinant TNF-related apoptosis inducing ligand (TRAIL 24 hours before OVA challenge. The total number of leukocytes and the levels of the chemokine CXCL-1/KC significantly increased in the bronchoalveolar lavage (BAL fluids of allergic animals with respect to control littermates, but not in the BAL of mice i.n. pretreated with recombinant TRAIL before OVA challenge. In particular, TRAIL pretreatment significantly reduced the BAL percentage of both eosinophils and neutrophils. On the other hand, when TRAIL was administrated simultaneously to OVA challenge its effect on BAL infiltration was attenuated. Overall, the results show that the i.n. pretreatment with TRAIL down-modulated allergic airway inflammation.

  7. Evaluation of intranasal vaccine administration and high-dose interferon- α2b therapy for treatment of chronic upper respiratory tract infections in shelter cats.

    Science.gov (United States)

    Fenimore, Audra; Carter, Kasey; Fankhauser, Jeffrey; Hawley, Jennifer R; Lappin, Michael R

    2016-08-01

    Clinical signs of upper respiratory tract infection can be hard to manage in cats, particularly those in shelters. In this study, clinical data were collected from chronically ill (3-4 weeks' duration) cats with suspected feline herpesvirus-1 (FHV-1) or feline calicivirus (FCV) infections after administration of one of two novel therapies. Group A cats were administered a commercially available formulation of human interferon-α2b at 10,000 U/kg subcutaneously for 14 days, and group B cats were administered one dose of a FHV-1 and FCV intranasal vaccine. Molecular assays for FHV-1 and FCV were performed on pharyngeal samples, and a number of cytokines were measured in the blood of some cats. A clinical score was determined daily for 14 days, with cats that developed an acceptable response by day 14 returning to the shelter for adoption. Those failing the first treatment protocol were entered into the alternate treatment group. During the first treatment period, 8/13 cats in group A (61.5%) and all 12 cats in group B (100%) had apparent responses. The seven cats positive for nucleic acids of FHV-1 or FCV responded favorably, independent of the treatment group. There were no differences in cytokine levels between cats that responded to therapy or failed therapy. Either protocol assessed here may be beneficial in alleviating chronic clinical signs of suspected feline viral upper respiratory tract disease in some cats that have failed other, more conventional, therapies. The results of this study warrant additional research involving these protocols. PMID:26269455

  8. Intranasal Administration of Type V Collagen Reduces Lung Carcinogenesis through Increasing Endothelial and Epithelial Apoptosis in a Urethane-Induced Lung Tumor Model.

    Science.gov (United States)

    Parra, Edwin Roger; Alveno, Renata Antunes; Faustino, Carolina Brito; Corrêa, Paula Yume Sato Serzedello; Vargas, Camilla Mutai; de Morais, Jymenez; Rangel, Maristela Peres; Velosa, Ana Paula Pereira; Fabro, Alexandre Todorovic; Teodoro, Walcy Rosolia; Capelozzi, Vera Luiza

    2016-08-01

    Type V collagen (Col V) is a "minor" component of normal lung extracellular matrix, which is subjected to decreased and abnormal synthesis in human lung infiltrating adenocarcinoma. We previously reported that a direct link between low amounts of Col V and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis. Moreover, this collagen species was able to trigger DNA fragmentation and impair survival of neoplastic cells. In this study, we have extended our investigation with the aim to obtain further evidence that the death induced by Col V-treatment is of the caspase-9 apoptotic type. We used (1) optical and electron microscopy, (2) quantitation of TUNEL-labeled cells and (3) analysis of the expression levels of Col V and selected genes coding for apoptosis-linked factors, by conventional RT-PCR. BALB/c mice were injected intraperitoneally with 1.5 g/kg body weight of urethane. After urethane injection, the animals received intranasal administration of 20 µg/20 µl of Col V every day during 2 months. We report here that Col V treatment was able to determine significant increase in Col V protein and gene expression and in the percentage of TUNEL-positive cells, to up-regulate caspase-9, resulting in low growth of tumor cells. Our data validate chemical carcinogenesis as a suitable "in vivo" model for further and more detailed studies on the molecular mechanisms of the death response induced by Col V in lung infiltrating adenocarcinoma opening new strategies for treatment. PMID:27020095

  9. Intranasal Administration of Type V Collagen Reduces Lung Carcinogenesis through Increasing Endothelial and Epithelial Apoptosis in a Urethane-Induced Lung Tumor Model.

    Science.gov (United States)

    Parra, Edwin Roger; Alveno, Renata Antunes; Faustino, Carolina Brito; Corrêa, Paula Yume Sato Serzedello; Vargas, Camilla Mutai; de Morais, Jymenez; Rangel, Maristela Peres; Velosa, Ana Paula Pereira; Fabro, Alexandre Todorovic; Teodoro, Walcy Rosolia; Capelozzi, Vera Luiza

    2016-08-01

    Type V collagen (Col V) is a "minor" component of normal lung extracellular matrix, which is subjected to decreased and abnormal synthesis in human lung infiltrating adenocarcinoma. We previously reported that a direct link between low amounts of Col V and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis. Moreover, this collagen species was able to trigger DNA fragmentation and impair survival of neoplastic cells. In this study, we have extended our investigation with the aim to obtain further evidence that the death induced by Col V-treatment is of the caspase-9 apoptotic type. We used (1) optical and electron microscopy, (2) quantitation of TUNEL-labeled cells and (3) analysis of the expression levels of Col V and selected genes coding for apoptosis-linked factors, by conventional RT-PCR. BALB/c mice were injected intraperitoneally with 1.5 g/kg body weight of urethane. After urethane injection, the animals received intranasal administration of 20 µg/20 µl of Col V every day during 2 months. We report here that Col V treatment was able to determine significant increase in Col V protein and gene expression and in the percentage of TUNEL-positive cells, to up-regulate caspase-9, resulting in low growth of tumor cells. Our data validate chemical carcinogenesis as a suitable "in vivo" model for further and more detailed studies on the molecular mechanisms of the death response induced by Col V in lung infiltrating adenocarcinoma opening new strategies for treatment.

  10. INTRANASAL DEXMEDETOMIDINE VS. INTRANASAL MIDAZOLAM FOR PREMEDICATION OF PAEDIATRIC SURGERY PATIENTS

    Directory of Open Access Journals (Sweden)

    Revi N

    2016-06-01

    Full Text Available AIM Preoperative anxiety is one of the most common problems faced by anyone practising paediatric anaesthesia. Various drugs have been used in various routes to get a calm but cooperative child before induction of anaesthesia. Midazolam and dexmedetomidine have already proved their value in paediatric premedication. This study was conducted to compare the effects of these two drugs given intranasally. MATERIALS AND METHODS 100 children falling under the inclusion criteria were assigned to groups of 50 each. They received either intranasal midazolam 0.2 mg/kg (group M or intranasal dexmedetomidine 2 mcg/kg (Group D as premedication. They were compared with regards to the sedation status, anxiety levels and cardiovascular status every 10 minutes, at parental separation and at face mask application. RESULTS The mean sedation score obtained at all-time intervals, at parental separation and more importantly at mask induction were much lower for the midazolam group compared to the dexmedetomidine group. The mean anxiety levels, in general, were lower in the midazolam group, but they attained statistical significance only at 10 minutes and at mask induction. The heart rate measured up to 20 minutes after drug administration did not show much difference between both groups, but at 30 minutes, 40 minutes and at parental separation, heart rate was found to be lower in the dexmedetomidine group. CONCLUSION Intranasal dexmedetomidine and intranasal midazolam are equally effective in providing satisfactory parental separation, but intranasal midazolam produced superior conditions for mask acceptance than intranasal dexmedetomidine.

  11. Activity increase in EpoR and Epo expression by intranasal recombinant human erythropoietin (rhEpo) administration in ischemic hippocampi of adult rats.

    Science.gov (United States)

    Castañeda-Arellano, R; Feria-Velasco, A I; Rivera-Cervantes, M C

    2014-11-01

    Erythropoietin in the nervous system is a potential neuroprotective factor for cerebral ischemic damage due to specific-binding to the erythropoietin receptor, which is associated with survival mechanisms. However, the role of its receptor is unclear. Thus, this work assessed whether a low dose (500UI/Kg) of intranasal recombinant human erythropoietin administered 3h after ischemia induced changes in the activation of its receptor at the Tyr456-phosphorylated site in ischemic hippocampi in rats. The results showed that recombinant human erythropoietin after injury maintained cell survival and was associated with an increase in receptor phosphorylation at the Tyr456 site as an initial signaling step, which correlated with a neuroprotective effect. PMID:25219375

  12. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    OpenAIRE

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2007-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day b...

  13. Spray dried microspheres based on chitosan: A promising new carrier for intranasal administration of polymeric antigen BLSOmp31 for prevention of ovine brucellosis.

    Science.gov (United States)

    Díaz, Alejandra Graciela; Quinteros, Daniela Alejandra; Llabot, Juan Manuel; Palma, Santiago Daniel; Allemandi, Daniel Alberto; Ghersi, Giselle; Zylberman, Vanesa; Goldbaum, Fernando Alberto; Estein, Silvia Marcela

    2016-05-01

    Previous studies have demonstrated that parenteral immunization with polymeric antigen BLSOmp31 induced a strong immune response and conferred protection against Brucella ovis in rams. This work describes the development of a novel formulation strategy for the delivery of BLSOmp31 in the nasal mucosa. Chitosan microparticles were prepared by spray-drying technology processes and recombinant chimera BLSOmp31 was loaded by passive adsorption onto chitosan microspheres, which were characterized by means of the evaluation of size, zeta potential, morphology, and loading and release rate of BLSOmp31. The mucoadhesive properties of microspheres were evaluated by studying the interaction between microparticles and mucin. The antigen BLSOmp31 integrity was investigated by SDS-PAGE. The yield of production of spray-drying process was 68.95%. Microspheres had a good sphericity, 1-10 μm of particle size and had a positive charge. The loading capacity was found to be 45.19%. The initial fast release of BLSOmp31 from chitosan microparticles was 60%. The BLSOmp31 integrity was not affected by passive adsorption (ionic interaction). The amount of mucin adsorbed on the surface of CMs-BLSOmp31 was lower than on the surface of blank CMs at neutral pH. In vivo studies were carried out in rams. Intranasal immunization induced systemic and local antibodies. In conclusion, the use of BLSOmp31-loaded chitosan spray-drying microspheres offers a promising way for nasal mucosal vaccination in sheep against brucellosis. PMID:26952451

  14. Analysis on brain targeting of scopolamine following intranasal administration by using solid phase extraction and LC/MS assay%固相萃取与液质联用法分析东莨菪碱经鼻腔给药的脑靶向性

    Institute of Scientific and Technical Information of China (English)

    李萍; 王化芬; 史卫峰; 刘兰兰; 刘卫

    2013-01-01

    Objective To investigate the distribution of scopolamine into brain following intranasal .Methods Adult Wistar rats were divided into two groups ,and administrated with scopolamine 0 .3 mg via intraperitoneal or intranasal respectively .Two groups of blood concentration and brain concentration of scopolamine were determined by solid phase extraction (SPE) and LC/MS assay at the time point of 5 ,10 ,20 ,30 ,60 ,120 ,240 ,480 min ,and their kinetic parameters were calculated and compared .Results Scopol-amine bioavailability of intranasal administration was 65% ,and the maximum concentration of scopolamine in brain following in-tranasal administration was much higher than that following intraperitoneal administration .Comparing the ratio of AUC in brain and in plasma ,ratio of intranasal administration is bigger than that of intraperitoneal administration significantly (P<0 .05) .Con-clusion It was concluded that scopolamine′s intranasal administration induced the agent targeting distribution into the brain .%目的:研究东莨菪碱经鼻腔给药的脑靶向性。方法将Wistar大鼠分为两组,分别通过腹腔和鼻腔给予0.3 mg东莨菪碱。用固相萃取和液质联用的方法测定在5、10、20、30、60、120、240、480 min血浆和脑组织匀浆中东莨菪碱的浓度,计算并比较腹腔和鼻腔给药后的药代动力学参数。结果东莨菪碱鼻腔给药的生物利用度为65%。经鼻腔给药后的脑药浓度大于经腹腔给药的脑药浓度,鼻腔给药东莨菪碱的脑药浓度与血药浓度的比值远大于腹腔给药后脑药浓度与血药浓度的比值(P<0.05)。结论东莨菪碱鼻腔给药具有脑靶向性。

  15. Transferrin receptor antibody-modified α-cobrotoxin-loaded nanoparticles enable drug delivery across the blood–brain barrier by intranasal administration

    International Nuclear Information System (INIS)

    A novel drug carrier for brain delivery, maleimide–poly(ethyleneglycol)–poly(lactide) (maleimide–PEG–PLA) nanoparticles (NPs) conjugated with mouse–anti-rat monoclonal antibody OX26 (OX26–NPs), was developed and its brain delivery property was evaluated. The diblock copolymers of maleimide–PEG–PLA were synthesized and applied to α-cobrotoxin (αCT)-loaded NPs which were characterized by transmission electron micrograph imaging, Fourier-transform IR, and X-ray diffraction. The NPs encapsulating αCT had a round and vesicle-like shape with a mean diameter around 100 nm, and the OX26 had covalently conjugated to the surface of NPs. MTT studies in brain microvascular endothelial cells (BMEC) revealed a moderate decrease in the cell viability of αCT, when incorporated in OX26–NPs compared to free αCT in solution. A higher affinity of the OX26–αCT–NPs to the BMEC was shown in comparison to αCT–NPs. Then, OX26–αCT–NPs were intranasally (i.n.) administered to rats, and αCT in the periaqueductal gray was monitored for up to 480 min using microdialysis technique in free-moving rats, with i.n. αCT–NPs, i.n. OX26–αCT–NPs, intramuscular injection (i.m.) αCT–NPs, and i.m. OX26–αCT–NPs. The brain transport results showed that the corresponding absolute bioavailability (Fabs) of i.n. OX26–αCT–NPs were about 125 and 155 % with i.n. αCT–NPs and i.m. OX26–αCT–NPs, respectively, and it was found that both the Cmax and AUC of the four groups were as follows: i.n. OX26–αCT–NPs > i.n. αCT–NPs > i.m. OX26–αCT–NPs > i.m. αCT–NPs, while αCT solution, as control groups, could hardly enter the brain. These results indicated that OX26–NPs are promising carriers for peptide brain delivery

  16. Glucose recovery after intranasal glucagon during hypoglycaemia in man.

    Science.gov (United States)

    Hvidberg, A; Djurup, R; Hilsted, J

    1994-01-01

    We compared the hyperglycaemic effect of intranasal and intramuscular (i.m.) administration of glucagon after insulin-induced hypoglycaemia. Twelve healthy subjects were examined twice, receiving on both occasions an intravenous insulin bolus. Somatostatin and propranolol were administered to block endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose to exceed 3 mmol.l-1 was significantly shorter for i.m. glucagon. The mean plasma glucagon level increased faster after i.m. glucagon than after intranasal glucagon, and the levels remained higher throughout the study period. We conclude that glucose recovery was significantly better after i.m. administration of glucagon than after intranasal administration. However, the differences between the incremental plasma glucose and the time for incremental plasma glucose to exceed 3 mmol.l-1 were not considered of major clinical importance. PMID:7911762

  17. Co-Administration of Chenopodium Album Allergens and CpG Oligodeoxy-nucleotides Effects on Peripheral Blood Mononuclear Cells of Patients with Allergic Rhinitis Treated with Intranasal Corticosteroids

    Directory of Open Access Journals (Sweden)

    Shokrollah Farrokhi

    2011-06-01

    Full Text Available Allergic Rhinitis (AR is one of the most common chronic diseases in the developed countries. This study was performed to investigate the effect of CpG-ODN in alteration of T-helper (Th1/Th2 balance of patients with AR treated with intranasal corticosteroids (INCs and antihistamines. Peripheral blood mononuclear cells (PBMCs of 20 patients with AR were isolated before and after 45 days therapy.Cytokine production (IL-4, IL-10, IL-13, IFN-γ and specific Ch.a IgE in response to CpG co- administration  of  natural  chenopodium  album  (CpG/Ch.a  or  recombinant  Ch.a  (CpG/rCh.a allergen were investigated in supernatants.of cultured PBMCs using ELISA Intracellular IL-10 was also assessed in CD4+ cells using flow cytometry. Significant increase in production of IFN-γ and IL-10 and decrease in production of IL-4 were found in supernatants of cultured PBMCs activated with CPG/ch.a and CPG/rch.a. of both CpG/Ch.a and CpG/rCh.a compared to allergens alone, before and after therapy.After therapy, IFN-γ production with CpG/Ch.a was significantly increased in comparison with before (237 vs. 44 pg/ml, p=0.001. IFN-γ and IL-10 production with CpG/rCh.a was significantly increased after therapy compared to before (407.6 vs. 109 pg/ml, p=0.01 for IFN-γ; 171.7 vs. 52.6 pg/ml, p=0.008  for  IL-10,  whilst  IL-4  was  significantly decreased (2.1  vs.  5.8  pg/ml,  p=0.02. Intracellular IL-10 expression was also significantly increased in response to either CpG/Ch.a or CpG/rCh.a that showed intracellular assay could be more sensitive than ELISA. Also, treatment with intranasal corticosteroids and antihistamines could enhance this CpG effect, in vitro.

  18. Intranasal mesenchymal stem cell treatment for neonatal brain damage : long-term cognitive and sensorimotor improvement

    NARCIS (Netherlands)

    Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; van Bel, Frank; Kas, Martien J H; Kavelaars, Annemieke; Heijnen, Cobi J

    2013-01-01

    Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic wi

  19. Demystifying FluMist, a new intranasal, live influenza vaccine.

    Science.gov (United States)

    Mossad, Sherif B

    2003-09-01

    FluMist--a cold-adapted, live-attenuated, trivalent, intranasal influenza virus vaccine approved by the US Food and Drug Administration on June 17, 2003--has been shown to be safe and effective, but its role in the general prevention of influenza is yet to be defined. Intranasal administration is expected to be more acceptable than parenteral, particularly in children, but the potential for the shedding of live virus may pose a risk to anyone with a compromised immune system. PMID:14518575

  20. Glucose recovery after intranasal glucagon during hypoglycaemia in man

    DEFF Research Database (Denmark)

    Hvidberg, A; Djurup, R; Hilsted, J

    1994-01-01

    to exceed 3 mmol.l-1 was significantly shorter for i.m. glucagon. The mean plasma glucagon level increased faster after i.m. glucagon than after intranasal glucagon, and the levels remained higher throughout the study period. We conclude that glucose recovery was significantly better after i......We compared the hyperglycaemic effect of intranasal and intramuscular (i.m.) administration of glucagon after insulin-induced hypoglycaemia. Twelve healthy subjects were examined twice, receiving on both occasions an intravenous insulin bolus. Somatostatin and propranolol were administered to block...... endogenous glucose counterregulation, and glucose turnover was estimated by a 3-[3H]-glucose infusion. When hypoglycaemia was reached, the subjects received either i.m. glucagon of pancreatic extraction (1 mg) or intranasal genetically engineered glucagon (2 mg). The incremental values for plasma glucose...

  1. Population Pharmacokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Wu, L.; Chow, D. S. L.; Putcha, L.

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  2. Intranasal curcumin and its evaluation in murine model of asthma.

    Science.gov (United States)

    Subhashini; Chauhan, Preeti S; Kumari, Sharda; Kumar, Jarajana Pradeep; Chawla, Ruchi; Dash, D; Singh, Mandavi; Singh, Rashmi

    2013-11-01

    Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been shown to have a wide variety of pharmacological activities including anti-inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for its low systemic bioavailability and rapid metabolization through oral route and has limited its applications. Over the recent decades, the interest in intranasal delivery as a non-invasive route for drugs has increased as target tissue for drug delivery since nasal mucosa offers numerous benefits. In this study, we evaluated intranasal curcumin following its absorption through nasal mucosa by a sensitive and validated high-performance liquid chromatography (HPLC) method for the determination of intranasal curcumin in mouse blood plasma and lung tissue. Intranasal curcumin has been detected in plasma after 15 min to 3 h at pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At considerably lower doses has proved better than standard drug disodium cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration and histamine release in mouse model of asthma. HPLC detection revealed that curcumin absorption in lungs has started after 30 min following intranasal administration and retained till 3h then declines. Present investigations suggest that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and detected in plasma and lungs both and suppressed airway inflammations at lower doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops to prevent airway inflammations and bronchoconstrictions in asthma without any side effect. PMID:24021755

  3. Role of intranasal fentanyl in breakthrough pain management in cancer patients

    Directory of Open Access Journals (Sweden)

    Wojciech Leppert

    2010-09-01

    Full Text Available Wojciech LeppertDepartment of Palliative Medicine, Poznan University of Medical Sciences, Poznan, PolandAbstract: Fentanyl is a strong opioid analgesic, which is commonly used in the form of a transdermal patch for the treatment of chronic cancer pain. An intranasal route of fentanyl administration is a novel treatment for breakthrough cancer pain (BTCP. The prevalence, assessment, and management of BTCP is outlined in this paper, and basic pharmacodynamic and pharmacokinetic properties, dosing guidelines, and clinical experience with the use of intranasal fentanyl in this indication are discussed. Intranasal fentanyl is an attractive and convenient mode of BTCP treatment in opioid-tolerant patients due to its quick onset and short duration of action, noninvasive administration route, high bioavailability, and avoidance of a hepatic first-pass effect. Until now, few clinical trials have been conducted with intranasal fentanyl, but all have confirmed its usefulness and acceptability in BTCP treatment. Intranasal fentanyl may be used in opioid-tolerant patients without nasal pathologies. The dose should be titrated in each patient regardless of the regular opioid dose administered. Future studies should compare intranasal fentanyl with other fentanyl formulations used for BTCP management, and with analgesia, adverse effects, and quality of life taken into consideration.Keywords: adverse effects, analgesia, breakthrough pain, intranasal fentanyl, opioid analgesics, treatment

  4. Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain.

    Science.gov (United States)

    Manda, Prashanth; Kushwaha, Avadhesh Singh; Kundu, Santanu; Shivakumar, H N; Jo, Seong Bong; Murthy, S Narasimha

    2016-02-28

    The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague-Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h(-1). The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h(-1) and 0.42±0.10h(-1) respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain. PMID:26732557

  5. Intranasal oxytocin increases social grooming and food sharing in the common vampire bat Desmodus rotundus.

    Science.gov (United States)

    Carter, Gerald G; Wilkinson, Gerald S

    2015-09-01

    Intranasal oxytocin (OT) delivery has been used to non-invasively manipulate mammalian cooperative behavior. Such manipulations can potentially provide insight into both shared and species-specific mechanisms underlying cooperation. Vampire bats are remarkable for their high rates of allogrooming and the presence of regurgitated food sharing among adults. We administered intranasal OT to highly familiar captive vampire bats of varying relatedness to test for an effect on allogrooming and food sharing. We found that intranasal OT did not have a detectable effect on food-sharing occurrence, but it did increase the size of regurgitated food donations when controlling for dyad and amount of allogrooming. Intranasal OT in females increased the amount of allogrooming per partner and across all partners per trial, but not the number of partners. We also found that the peak effect of OT treatments occurred 30-50min after administration, which is consistent with the reported latency for intranasal OT to affect relevant brain areas in rats and mice. Our results suggest that intranasal OT is a potential tool for influencing dyadic cooperative investments, but measuring prior social relationships may be necessary to interpret the results of hormonal manipulations of cooperative behavior and it may be difficult to alter partner choice in vampire bats using intranasal OT alone. PMID:26475061

  6. Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs.

    Science.gov (United States)

    Ellis, J A; Gow, S P; Waldner, C L; Shields, S; Wappel, S; Bowers, A; Lacoste, S; Xu, Z; Ball, E

    2016-06-01

    In order to determine the comparative efficacy of vaccines administered intranasally or orally to protect puppies from disease subsequent to experimental infection with Bordetella bronchiseptica (Bb), a randomized controlled trial was performed using 48 approximately 8-week-old specific pathogen free, Bb naive Beagle puppies. Puppies were randomized into three groups and administered vaccines containing Bb intranasally or orally, or a placebo intranasally. Twenty-one days later, all dogs were challenge exposed via aerosol administration of Bb. Clinical signs, nasal bacterial shedding and immune responses were monitored for 28 days after challenge. Intranasally vaccinated puppies had significantly lower rates of coughing, nasal discharge, retching and sneezing (i.e. were less sick clinically) than control puppies. The distinction between the orally vaccinated puppies and the control puppies was less consistent. The orally vaccinated puppies had less coughing and less retching than the control puppies, but nasal discharge and sneezing did not differ from control animals. Orally vaccinated puppies had higher rates of coughing, nasal discharge, retching and sneezing than the intranasally vaccinated puppies. Although both intranasal and oral Bb vaccines stimulated immune responses associated with disease sparing following Bb infection, the intranasal route of delivery conferred superior clinical outcomes. The observed difference in clinical efficacy suggests the need to question the rationale for the use of currently available orally administered Bb vaccines. PMID:27256028

  7. Intranasal oxytocin increases social grooming and food sharing in the common vampire bat Desmodus rotundus.

    Science.gov (United States)

    Carter, Gerald G; Wilkinson, Gerald S

    2015-09-01

    Intranasal oxytocin (OT) delivery has been used to non-invasively manipulate mammalian cooperative behavior. Such manipulations can potentially provide insight into both shared and species-specific mechanisms underlying cooperation. Vampire bats are remarkable for their high rates of allogrooming and the presence of regurgitated food sharing among adults. We administered intranasal OT to highly familiar captive vampire bats of varying relatedness to test for an effect on allogrooming and food sharing. We found that intranasal OT did not have a detectable effect on food-sharing occurrence, but it did increase the size of regurgitated food donations when controlling for dyad and amount of allogrooming. Intranasal OT in females increased the amount of allogrooming per partner and across all partners per trial, but not the number of partners. We also found that the peak effect of OT treatments occurred 30-50min after administration, which is consistent with the reported latency for intranasal OT to affect relevant brain areas in rats and mice. Our results suggest that intranasal OT is a potential tool for influencing dyadic cooperative investments, but measuring prior social relationships may be necessary to interpret the results of hormonal manipulations of cooperative behavior and it may be difficult to alter partner choice in vampire bats using intranasal OT alone.

  8. 单次鼻滴入油酸对SD大鼠的呼吸系统急性损伤作用%Acute Respiratory Injury on Rats after A Single Intranasal Administration of Oleic Acid

    Institute of Scientific and Technical Information of China (English)

    胡天羽; 李华; 马璟

    2013-01-01

    Seventy SD rats were randomly divided into the following 5 groups: blank control, bleomycin (5 mg/kg) and oleic acid (12, 60 and 120 mg/kg) groups. All test animals were administered intranasally at a single dose. Their respiratory rate (RR), tidal volume (TV) and minute volume (MV) were recorded by computer at 0.5, 1, 2, 4 and 8 h after administration. The animals were sacrificed in three batches on d3, d7, d21. The respiratory toxicity effect of oleic acid was evaluated according to total and classified inflammatory cell count, protein concentration and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF) of the left lobe of lung. The hydroxyproline (HYP) content in right upper lobe of lung was determined and the histopathologic changes of right lower lobe were observed. The results showed that the RR level at 0.5 h of three oleic acid groups were obviously higher than that of blank control group, while the TV level were lower. Compared with the blank control group, the total number of inflammatory cells, neutrophilic granulocyte, eosinophilic granulocytes, protein concentration and LDH activity in BALF in high dose group of oleic acid were significantly increased and lung section showed inflammatory response and numerous foam cells. There were no significant differences between three oleic acid groups and blank control group in HYP content. It indicated that high dose of oleic acid had an acute injury on rat lung tissue and affected the respiratory function, but this effect was normally reversible.%将SD大鼠70只随机分为阴性对照组、博来霉素(5 mg/kg)对照组和油酸3个剂量(12、60和120 mg/kg)组,均采用单剂量鼻滴入给药.测定给药后0.5、1、2、4和8h时动物的呼吸频率、潮气量和每分通气量.给药后d3、d7和d21分批处死动物.取左肺叶进行支气管肺泡灌洗,进行灌洗液(BALF)中炎症细胞总数和分类计数,并测定全蛋白浓度和乳酸脱氢酶(LDH)活性;另取

  9. Intranasal Fentanyl for Analgesia in Adults with Acute Renal Colic

    OpenAIRE

    Massimiliano Etteri; Andrea Bellone

    2012-01-01

    Objectives: The usual treatment of pain in acute renal colic is analgesic in intravenous (IV) route. We tried a rapid, non painful, non-invasive route of administration using intranasal fentanyl versus IV standard treatment (non steroidal anti-inflammatory drug (NSAIDs) plus morphine) for the relief of pain in renal colic presenting to an Emergency Department (ED). Methods: We conducted a prospective non-blinded randomized clinical trial. A sample of 63 adult patients with clinical diagnosis ...

  10. Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

    Science.gov (United States)

    Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

    2012-01-01

    Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

  11. The experimental study of calcitonin gene-related peptide intranasal administration to central nervous system and prompt the repair of cerebral infarct%降钙素基因相关肽经鼻给药进入中枢神经系统及促脑梗死修复的实验性研究

    Institute of Scientific and Technical Information of China (English)

    吴庆建; 闫承军; 宋大庆; 刘云海; 孙树印

    2014-01-01

    Objective To develoP a convenient and effective method for delivering CGRP to the central nervous system byPassing the blood-brain barrier( BBB),and to exPlore whether it had Preventive and Protective effects on cerebral in-farction in rats. Methods The MCAO model was made by nylon strand. CGRP concentration was measured IN and IV in-jection of CGRP after 30 min in different brain areas using enzyme-linked immunosorbent assay( ELISA),and exPlored the treatment IN and IV CGRP in rats with focal cerebral infarction. Results CGRP demonstrated a much higher delivery of IN than IV CGRP to the brain regions. Intranasal administration CGRP had significant Preventive and Protective effect to focal cerebral infarction which showed the brain infarction decreased and cerebral blood flow increased( P<0. 01 ). Conclusion CGRP intranasal administration targeting central administration can avoid the blood-brain barrier block,and had Preven-tive and Protective effects on the rats with focal cerebral infarction. Intranasal administration CGRP had definite Preventive and Protective effect to focal cerebral infarction in rats.%目的:寻找快速、便捷有效的靶向中枢给药方法,为脑梗死治疗提供新的思路。方法线栓法制作大鼠大脑中动脉闭塞( Middle cerebral artery occlusion,MCAO)脑缺血再灌注模型,采用ELISA法测定经鼻( IN)和静脉( IV)注射CGRP后30 min时,各脑区的CGRP浓度,并观察IN和IV给予CGRP对局灶性脑梗死的治疗效果。结果 IN给药组脑部各区域、颈髓和脑脊液(Cerebro-sPinal fluid,CSF)中CGRP浓度较IV组显著增高(P<0.01),与IV组相比较,IN给药组梗死体积减小,脑血流量增加( P<0.01)。结论 CGRP经鼻靶向中枢给药可以避开血脑屏障阻碍,并对大鼠局灶性脑梗死有预防和保护作用。

  12. The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS.

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    Robert A Scranton

    Full Text Available BACKGROUND: The blood brain barrier (BBB is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS, but the relative contributions are debated. METHODS AND FINDINGS: In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum. CONCLUSIONS: This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before we are able to advance this technique into human research.

  13. Preparation and evaluation of fexofenadine microemulsion for intranasal delivery.

    Science.gov (United States)

    Piao, Hong-Mei; Balakrishnan, Prabagar; Cho, Hyun Jong; Kim, Hyunjun; Kim, You Sun; Chung, Suk-Jae; Shim, Chang-Koo; Kim, Dae-Duk

    2010-06-01

    To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol oleiqueCC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64mg/mL) and F2 (22.98mg/mL), compared to its intrinsic water solubility (1.51mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. T(max) was observed within 5min after intranasal administration at 1.0mg/kg dose, and the absolute bioavailability (0-4h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine. PMID:20685383

  14. Preparation and evaluation of fexofenadine microemulsions for intranasal delivery.

    Science.gov (United States)

    Piao, Hong-Mei; Balakrishnan, Prabagar; Cho, Hyun-Jong; Kim, Hyunjun; Kim, You-Sun; Chung, Suk-Jae; Shim, Chang-Koo; Kim, Dae-Duk

    2010-08-16

    To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol Oleique CC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64 mg/mL) and F2 (22.98 mg/mL), compared to its intrinsic water solubility (1.51 mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. Tmax was observed within 5 min after intranasal administration at 1.0 mg/kg dose, and the absolute bioavailability (0-4 h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine PMID:20635476

  15. Iatrogenic Cushing's Syndrome Due to Intranasal Usage of Ophthalmic Dexamethasone: A Case Report.

    Science.gov (United States)

    Orton, Sarah; Censani, Marisa

    2016-05-01

    Iatrogenic Cushing's syndrome (ICS) is caused by exogenous corticosteroid administration with suppression of the hypothalamic-pituitary-adrenal axis. It has been commonly described with oral and topical steroid use, but scarce reports have documented intranasal steroid usage as the etiology in infancy. In this article, we describe a case of a 4-month-old infant who developed ICS after 6 weeks of intranasal dexamethasone ophthalmic solution administration for nasal obstruction. To our knowledge, this is the youngest patient reported with ICS due to intranasal use of a prescribed dose of an ophthalmic steroid. His hypothalamic-pituitary-adrenal axis recovered fully 4.5 months after steroid discontinuation. Because of the small body surface area and supine position during administration, infants are particularly susceptible to ICS. Given that intranasal steroids are commonly prescribed to infants and children for a variety of diagnoses, this case highlights the risks inherent in the use of intranasal steroid drops, particularly in young infants, for both adrenal suppression and linear growth deceleration, even with short-term use. Close monitoring of these patients' height and weight should occur while on steroid treatment, with every effort made to decrease or discontinue steroid use when possible. PMID:27244810

  16. Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

    Science.gov (United States)

    Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

  17. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    Science.gov (United States)

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2008-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day blocks of sessions; each block was separated by at least 24 hrs. At approximately 1000 hrs, on the first day of each block, participants received one of four intranasal methamphetamine doses (0, 12, 25, 50 mg/70 kg). Lights were turned out at 2300 hrs that evening and sleep measures were assessed. On the morning of the second day of each block, methamphetamine plasma levels, cardiovascular measures, mood, subjective reports of the previous evening's sleep, and psychomotor performance were assessed to determine residual drug effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted subjective measures of that night's sleep and some indices of next-day mood, but only the largest dose (50 mg) dose decreased objective measures of that night's sleep and increased next-day physiological measures. Methamphetamine did not produce any negative residual effects on early next-day performance. Future studies should assess methamphetamine-related residual effects following repeated doses administered over consecutive days. PMID:18078723

  18. CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

    Directory of Open Access Journals (Sweden)

    Olga Dal Monte

    Full Text Available Oxytocin (OT in the central nervous system (CNS influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline to 15 primates (Macaca mulatta, using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

  19. Evaluation of the effectiveness and safety of chitosan derivatives as adjuvants for intranasal vaccines.

    Science.gov (United States)

    Kobayashi, Takashi; Fukushima, Kenji; Sannan, Takanori; Saito, Noriko; Takiguchi, Yasuyuki; Sato, Yuko; Hasegawa, Hideki; Ishikawa, Koichi

    2013-04-01

    Intranasal immunization is currently used to deliver live virus vaccines such as influenza. However, to develop an intranasal vaccine to deliver inactivated virus, a safe and effective adjuvant is necessary to enhance the mucosal immune response. Here, we demonstrate the effectiveness of a chitosan microparticle (1-20 μm, 50 kDa, degree of deacetylation=85%) and a cationized chitosan (1000 kDa, degree of deacetylation=85%) derived from natural crab shells as adjuvants for an intranasal vaccine candidate. We examined the effectiveness of chitosan derivatives as an adjuvant by co-administering them with ovalbumin (OVA) intranasally in BALB/c mice, polymeric Ig receptor knockout (pIgR-KO) mice, and cynomolgus monkeys (Macaca fascicularis). pIgR-KO mice were used to evaluate S-IgA production on the mucosal surface without nasal swab collection. Administration of OVA with chitosan microparticles or cationized chitosan induced a high OVA-specific IgA response in the serum of pIgR-KO mice and a high IgG response in the serum of BALB/c mice and cynomolgus monkeys. We also found that administration of chitosan derivatives did not have a detrimental effect on cynomolgus monkeys as determined by complete blood count, blood chemistries, and gross pathology results. These results suggest that chitosan derivatives are safe and effective mucosal adjuvants for intranasal vaccination.

  20. Evaluation of Intranasal Ostium in External Dacryocystorhinostomy

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    Özlem Yalçın Tök

    2011-11-01

    Full Text Available Objective: The investigation of factors affecting the dimension and configuration of the intranasal ostium in successful external dacryocystorhinostomy (DCR. Material and Methods: Fifty-one patients were enrolled within this study. During operation, dimensions of bone window were measured. In the postoperative sixth month, changes in bone window size were evaluated using spiral paranasal tomography, and the intranasal ostium was examined with nasal endoscopy. Results: There were 19 patients who underwent DCR and 32 patients who underwent DCR+silicone tube intubations (SI. The mean bone window size was 214.37 mm2 during operation and 214.87 mm2 after six months. The mean intranasal ostium size was measured as 51.42 mm2 for patients who had undergone DCR and 28.66 mm2 for the DCR+SI cases. The endoscopic appearance of the ostium was observed as oval or round for the DCR cases and in slit form for the DCR+SI cases. A multiple logistic regression model showed that silicon tube intubation posed an 11 times greater risk for configuration distortion in the intranasal ostium (p=0.0079.Conclusion: Postoperative intranasal ostium size has a relation with the intraoperative bone window size. The difference of mean intranasal ostium sizes of DCR and DCR+SI cases was not statistically significant. However, because SI gives rise to ostium configuration by triggering fibrosis, it should not be carried out unless absolutely necessary.

  1. Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)

    Science.gov (United States)

    Boyd, Jason L.; Du, Brian; Daniels, Vernie; Simmons, Rita; Buckey, Jay; Putcha, Lakshmi

    2009-01-01

    Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on

  2. Live attenuated intranasal influenza vaccine.

    Science.gov (United States)

    Esposito, Susanna; Montinaro, Valentina; Groppali, Elena; Tenconi, Rossana; Semino, Margherita; Principi, Nicola

    2012-01-01

    Annual vaccination is the most effective means of preventing and controlling influenza epidemics, and the traditional trivalent inactivated vaccine (TIV) is by far the most widely used. Unfortunately, it has a number of limitations, the most important of which is its poor immunogenicity in younger children and the elderly, the populations at greatest risk of severe influenza. Live attenuated influenza vaccine (LAIV) has characteristics that can overcome some of these limitations. It does not have to be injected because it is administered intranasally. It is very effective in children and adolescents, among whom it prevents significantly more cases of influenza than the traditional TIV. However, its efficacy in adults has not been adequately documented, which is why it has not been licensed for use by adults by the European health authorities. LAIV is safe and well tolerated by children aged > 2 y and adults, but some concerns arisen regarding its safety in younger children and subjects with previous asthma or with recurrent wheezing. Further studies are needed to solve these problems and to evaluate the possible role of LAIV in the annual vaccination of the general population.

  3. Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant

    NARCIS (Netherlands)

    Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W

    2010-01-01

    Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often as

  4. Intranasal Rapamycin Rescues Mice from Staphylococcal Enterotoxin B-Induced Shock

    Directory of Open Access Journals (Sweden)

    Teresa Krakauer

    2012-09-01

    Full Text Available Staphylococcal enterotoxin B (SEB and related exotoxins produced by Staphylococcus aureus are potent activators of the immune system and cause toxic shock in humans. Currently there is no effective treatment except for the use of intravenous immunoglobulins administered shortly after SEB exposure. Intranasal SEB induces long-lasting lung injury which requires prolonged drug treatment. We investigated the effects of rapamycin, an immunosuppressive drug used to prevent graft rejection, by intranasal administration in a lethal mouse model of SEB-induced shock. The results show that intranasal rapamycin alone delivered as late as 17 h after SEB protected 100% of mice from lethal shock. Additionally, rapamycin diminished the weight loss and temperature fluctuations elicited by SEB. Intranasal rapamycin attenuated lung MCP-1, IL-2, IL-6, and IFNγ by 70%, 30%, 64%, and 68% respectively. Furthermore, short courses (three doses of rapamycin were sufficient to block SEB-induced shock. Intranasal rapamycin represents a novel use of an immunosuppressant targeting directly to site of toxin exposure, reducing dosages needed and allowing a wider therapeutic window.

  5. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.

    Science.gov (United States)

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel ('nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination. PMID:20562880

  6. Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

    Science.gov (United States)

    Harmon, Brendan Trevor

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic A9 nigrostriatal tract. For dopamine neurons specifically, glial cell-derived neurotrophic factor (GDNF) has been shown to promote their survival and proliferation both in culture and in vivo. GDNF has also proven to be neuroprotective and restorative in various animal models of PD and some human clinical trials. However, its delivery to the brain has required invasive surgical routes which are not clinically practical for many patients. The main objective of this project was to test intranasal delivery to the brain of a nanoparticle vector incorporating an expression plasmid for GDNF (pGDNF). The intranasal route circumvents the blood-brain barrier, allowing larger sized vectors into the central nervous system while avoiding peripheral distribution. This approach would provide a renewable source of GDNF within the target areas of the brain, the striatum and the substantia nigra (SN) without the need for surgical injections or frequent re-dosing. A PEGylated polylysine compacted plasmid nanoparticle vector (PEG-CK30), developed by Copernicus Therapeutics, Inc., has been shown to transfect neurons and glial cells in vivo while lacking the safety issues present with other vectors. The first goal of this work was to determine if these PEG-CK30 compacted plasmid nanoparticles can successfully transfect cells and express the reporter protein, enhanced green fluorescent protein (eGFP) in the rat brain after intranasal administration. Initial in vivo experiments utilized the expression plasmid pCG, expressing eGFP under the fast-acting cytomegalovirus (CMV) promoter. Intranasal administration of pCG nanoparticles resulted in evidence of transfection of brain cells, as shown both qualitatively, by GFP-immunohistochemistry, and quantitatively, by GFP-ELISA. Expression was detected throughout the rat brain two days post-administration. Following the proof

  7. Intranasal glucagon: a promising approach for treatment of severe hypoglycemia.

    Science.gov (United States)

    Pontiroli, Antonio E

    2015-01-01

    Prevention of diabetic complications is mainly obtained through optimal control of blood glucose levels. With hypoglycemic drugs like beta-cell stimulating drugs and especially insulin, the limit to treatment is represented by hypoglycemia, a life-threatening occurrence that is dangerous itself and can induce fear of other episodes. Glucagon, injected subcutaneously (SC) or intramuscularly (IM), is the treatment of choice for severe hypoglycemia outside of the hospital setting. However, due to practical aspects such as preparation of solutions for administration and injection by untrained persons, there are obstacles to its routine use. This review focuses on the current status of alternative routes of administration of peptide hormones, and in particular the intranasal (IN) route of glucagon, as a promising approach for the treatment of severe hypoglycemia. PMID:25385946

  8. Naloxone: intravenously, intramuscular, inhalatory and intranasal use in emergency cases

    Directory of Open Access Journals (Sweden)

    Carlo Locatelli

    2005-10-01

    Full Text Available The use of naloxone in emergency medicine is primarily connected to the treatment of a syndrome known as overdose, which is cause by non-essential use of heroin and certain opioid agonists. The dose of naloxone required to be efficacious depends on the quantity of opioid assumed, its receptorial affinity and its kinetics: in propoxyphene and pentazocine intoxication, for instance, higher doses are require than those needed in the treatment of morphine or heroin overdose. Intravenous administration is the most efficacious and fast-acting method: however, in certain cases, and depending on aspects that are typical of overdose patient management (e.g. the difficulties connected to vein access, skin scarring, severe hypotension, alternative pathways may be used. These include intraand sub-lingual and intratracheale administration, inhalatory administration via nebulisation (possible in the presence of respiratory action only, and intramuscular and subcutaneaous administration (which are efficacious in the absence of hypoperfusion. However, the most promising means of administration would appear to be intranasal administration, thanks to the relative ease of access, lower risk of contact with bodily fluids and the excellent bioavailability and rapidity of the effect, which is similar to that achieved with intravenous administration.

  9. Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Luigi Aloe; Patrizia Bianchi; Alberto De Bellis; Marzia Soligo; Maria Luisa Rocco

    2014-01-01

    The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

  10. Cilioretinal artery occlusion following intranasal cocaine insufflations

    Directory of Open Access Journals (Sweden)

    Balaji Kannan

    2011-01-01

    Full Text Available Cocaine is used to produce a euphoric effect by abusers, who may be unaware of the devastating systemic and ocular side effects of this drug. We describe the first known case of cilioretinal artery occlusion after intranasal cocaine abuse.

  11. Intranasal treatment of central nervous system dysfunction in humans.

    Science.gov (United States)

    Chapman, Colin D; Frey, William H; Craft, Suzanne; Danielyan, Lusine; Hallschmid, Manfred; Schiöth, Helgi B; Benedict, Christian

    2013-10-01

    One of the most challenging problems facing modern medicine is how to deliver a given drug to a specific target at the exclusion of other regions. For example, a variety of compounds have beneficial effects within the central nervous system (CNS), but unwanted side effects in the periphery. For such compounds, traditional oral or intravenous drug delivery fails to provide benefit without cost. However, intranasal delivery is emerging as a noninvasive option for delivering drugs to the CNS with minimal peripheral exposure. Additionally, this method facilitates the delivery of large and/or charged therapeutics, which fail to effectively cross the blood-brain barrier (BBB). Thus, for a variety of growth factors, hormones, neuropeptides and therapeutics including insulin, oxytocin, orexin, and even stem cells, intranasal delivery is emerging as an efficient method of administration, and represents a promising therapeutic strategy for the treatment of diseases with CNS involvement, such as obesity, Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, anxiety, autism spectrum disorders, seizures, drug addiction, eating disorders, and stroke. PMID:23135822

  12. Brain delivery of intranasal in situ gel of nanoparticulated polymeric carriers containing antidepressant drug: behavioral and biochemical assessment.

    Science.gov (United States)

    Kaur, Prabhjot; Garg, Tarun; Vaidya, Bhuvaneshwar; Prakash, Atish; Rath, Goutam; Goyal, Amit K

    2015-04-01

    This study was aimed for brain delivery of Tramadol HCl (centrally acting synthetic opioid) following intranasal administration for treatment of depression. Chitosan nanoparticles (NPs) were prepared by ionic gelation method followed by the addition of developed NPs with in the Pluronic and HPMC-based mucoadhesive thermo-reversible gel. Developed formulation optimized based on the various parameters such as particle size, entrapment efficiency, in vitro release study. Depression induction was done by forced swim test and evaluated by various behavioral and biochemical parameters. Furthermore, results showed significantly increased in locomotors activity, body weight as compared to control group. It also showed alteration in biochemical parameters such glutathione level and catalase levels significantly increased other than lipid peroxidation and nitrite level was found to be decreased after intranasal administration of formulation. Thus, intranasal TRM HCl NP-loaded in situ gel was found to be a promising formulation for the treatment of depression.

  13. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  14. 白细胞介素-10分子佐剂增强口蹄疫DNA疫苗黏膜免疫效果研究%Co-administration Intranasally the FMDV DNA Vaccine and the Constructed Expressing IL-10 as the Molecular Adjuvant in Enhancement of Mucosal Immune Responses in Murine Model

    Institute of Scientific and Technical Information of China (English)

    王潇; 王志钢; 杜瑞平

    2011-01-01

    [Objective] An experiment was carried out to investigate whether co-administration intranasally of the FMDV DNA vaccine, pcD-VPl and a construct expressing IL-10 as the molecular adjuvant can enhance mucosal immune responses in murine model. [Method] proVAX-IL-10 recombinant plasmid was constructed for eukarytic expression, then the mice were randomly divided into 5 groups and they were immunized I.n. with pcD-VPl alone or co-immunized with the provax-IL-10 molecular adjuvant on days 0,14 and 28. After immunization, mucosal slgA ,T cell proliferation and the expession of cytokines were deteced by ELISA, CFSE staining and intracellular cytokine staining method, respectively. [Result] Compared to the group intranasally immunized with pcD-VPl alone, the group immunized with the molecular adjuvant was induced higher level of mucosal slgA, and intranasal delivery of the IL-10 con struct with pcD-VPl significantly enhanced the higher level of antigen specific T cell proliferation and higher expession IL-4 in CD4+ cells inform mucosal site compared to the pcD-VPl alone. [Conclusion] The results demonstrated that intranasal delivery of IL-10 as a mucosal adjuvant can enhance the antigen specific mucosal immuneresponses in a murine model, which may provide a protection against the FMDV initial infection.%[目的]研究白细胞介素-10作为黏膜分子佐剂是否可以增强口蹄疫DNA疫苗(pcD-VP1)的黏膜免疫应答.[方法]利用RT-PCR技术以Balb/c小鼠脾脏组织总RNA为模板,扩增出小鼠的IL-10基因,并构建真核表达质粒proVAX-IL-10,通过鼻腔接种方式,将口蹄疫DNA疫苗(pcD-VP1)和真核表达质粒(proVAX-IL-10)共同免疫小鼠,用ELISA法检测免疫小鼠黏膜部位(肺脏,生殖道)sIgA滴度,免疫组织化学法检测气管、生殖道和小肠中sIgA的表达情况,CSFE染色法检测小鼠扁桃体淋巴细胞增殖反应水平,用胞内细胞因子染色法通过流式细胞仪检测扁桃体部位CD4

  15. Development of biodegradable starch microspheres for intranasal delivery

    Directory of Open Access Journals (Sweden)

    Yadav A

    2008-01-01

    Full Text Available Domperidone microspheres for intranasal administration were prepared by emulsification crosslinking technique. Starch a biodegradable polymer was used in preparation of microspheres using epichlorhydrine as cross-linking agent. The formulation variables were drug concentration and polymer concentration and batch of drug free microsphere was prepared for comparisons. All the formulations were evaluated for particle size, morphological characteristics, percentage drug encapsulation, equilibrium swelling degree, percentage mucoadhesion, bioadhesive strength, and in vitro diffusion study using nasal cell. Spherical microspheres were obtained in all batches with mean diameter in the range of above 22.8 to 102.63 μm. They showed good mucoadhesive property and swelling behaviour. The in vitro release was found in the range of 73.11% to 86.21%. Concentration of both polymer and drug affect in vitro release of drug.

  16. INTRANASAL LIPOSOMES : AN APPROACH FOR DRUG DELIVERY TO BRAIN

    Directory of Open Access Journals (Sweden)

    Mr. Jatin B. Trivedi

    2012-05-01

    Full Text Available Targeting drug molecules to brain is one of the most challenging research areas in pharmaceuticalsciences. Drugs that are effective against diseases in the CNS and reach the brain via the bloodcompartment must pass the BBB. The blood-brain barrier (BBB represents an insurmountable obstaclefor a large number of drugs, including antibiotics, anti-neoplastic agents, and a variety of central nervoussystem (CNS-active drugs. Therefore, various strategies have been proposed to improve the delivery ofdifferent drugs to this tissue which includes liposomes, colloidal drug carriers, micelles, chimericpeptide technology, intranasal and olfactory route of administration and nano technology. The discoveryof liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration; liposomedrug delivery systems have played a significant role in formulation of potent drug to improvetherapeutics Liposomes have been investigated as carriers of various pharmacologically active agentssuch as antineoplastic, antimicrobial drugs, chelating agents, steroids, vaccines, and genetic materials.Liposomes provide an efficient drug delivery system because they can alter the pharmacokinetics andpharmacodynamics of the entrapped drugs. Liposomes have been widely used for brain delivery in vivo.Nowadays, the nasal route for systemic drug delivery has gained great interest. It provides severaladvantages over other routes of drug administrations, which includes rapid absorption, avoids intestinaland hepatic presystemic disposition and high potential for drug transfer to the CSF. Moreover, the nasalroute is a potential alternative route for systemic availability of drugs restricted to intravenousadministration, viz. peptide and protein drugs and vaccines. As well, intranasal route has also beensuccessfully exploited for bypassing the blood brain barrier [BBB] and subsequently delivering drugmolecules to central nervous system [CNS].

  17. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    Science.gov (United States)

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-01

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  18. Postexposure Prophylaxis against Anthrax: Evaluation of Various Treatment Regimens in Intranasally Infected Guinea Pigs

    OpenAIRE

    Altboum, Zeev; Gozes, Yehoshua; Barnea, Ada; Pass, Avi; White, Moshe; Kobiler, David

    2002-01-01

    The efficiency of postexposure prophylaxis against Bacillus anthracis infection was tested in guinea pigs infected intranasally with either Vollum or strain ATCC 6605 spores (75 times the 50% lethal dose [LD50] and 87 times LD50, respectively). Starting 24 h postinfection, animals were treated three times per day for 14 days with ciprofloxacin, tetracycline, erythromycin, cefazolin, and trimethoprim-sulfamethoxazole (TMP-SMX). Administration of cefazolin and TMP-SMX failed to protect the anim...

  19. Evaluation of brain targeting efficiency of intranasal microemulsion containing olanzapine: pharmacodynamic and pharmacokinetic consideration.

    Science.gov (United States)

    Patel, Rashmin B; Patel, Mrunali R; Bhatt, Kashyap K; Patel, Bharat G; Gaikwad, Rajiv V

    2016-01-01

    The objective of this study was to develop and evaluate olanzapine (OZP) -loaded microemulsions (OZPME) for intranasal delivery in the treatment of schizophrenia. The OZPME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine - induced compulsive behavior and spontaneous locomotor activity) were performed using mice. All formulations were radiolabeled with technetium-99 ((99m)Tc), and biodistribution of drug in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rabbits was performed to determine the uptake of the OZP into the brain. OZPME were found clear and stable with average globule size of 23.87 ± 1.07 nm. In pharmacodynamic assessments, significant (p < 0.05) difference in parameters estimated were found between the treated and control groups. (99m)Tc-labeled OZP solution (OZPS)/OZPME/OZP mucoadhesive microemulsion (OZPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of OZPMME compared to intravenous OZPME was found to be five to six times higher signifying larger extent of distribution of the OZP in brain. Drug targeting efficiency and direct drug transport were found to be highest for intranasal OZPMME, compared to intravenous OZPME. Furthermore, rabbit brain scintigraphy also demonstrated higher intranasal uptake of the OZP into the brain. This investigation demonstrates a prompt and larger extent of transport of OZP into the brain through intranasal OZPMME, which may prove beneficial for treatment of schizophrenia. PMID:24845478

  20. A prospective randomised double-blinded study of intranasal midazolam atomizer spray for procedural sedation in paediatric patients

    Directory of Open Access Journals (Sweden)

    Vijaykumara

    2016-09-01

    Conclusions: We can thereby say that administration of preservative free intranasal midazolam atomizer spray in dose of 0.2mg/kg as premedication in paediatric patients produces satisfactory level of sedation and anxiolysis with minimal adverse effects. [Int J Res Med Sci 2016; 4(9.000: 3850-3854

  1. Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

    Directory of Open Access Journals (Sweden)

    Surjyanarayan Mandal

    2015-09-01

    Full Text Available This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS. The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

  2. Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus

    DEFF Research Database (Denmark)

    Hilsted, J C; Madsbad, S; Rasmussen, M H;

    1996-01-01

    Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods...... subcutaneous doses. The frequency of hypoglycemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosal physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment...

  3. Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

    Science.gov (United States)

    Harmon, Brendan Trevor

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic A9 nigrostriatal tract. For dopamine neurons specifically, glial cell-derived neurotrophic factor (GDNF) has been shown to promote their survival and proliferation both in culture and in vivo. GDNF has also proven to be neuroprotective and restorative in various animal models of PD and some human clinical trials. However, its delivery to the brain has required invasive surgical routes which are not clinically practical for many patients. The main objective of this project was to test intranasal delivery to the brain of a nanoparticle vector incorporating an expression plasmid for GDNF (pGDNF). The intranasal route circumvents the blood-brain barrier, allowing larger sized vectors into the central nervous system while avoiding peripheral distribution. This approach would provide a renewable source of GDNF within the target areas of the brain, the striatum and the substantia nigra (SN) without the need for surgical injections or frequent re-dosing. A PEGylated polylysine compacted plasmid nanoparticle vector (PEG-CK30), developed by Copernicus Therapeutics, Inc., has been shown to transfect neurons and glial cells in vivo while lacking the safety issues present with other vectors. The first goal of this work was to determine if these PEG-CK30 compacted plasmid nanoparticles can successfully transfect cells and express the reporter protein, enhanced green fluorescent protein (eGFP) in the rat brain after intranasal administration. Initial in vivo experiments utilized the expression plasmid pCG, expressing eGFP under the fast-acting cytomegalovirus (CMV) promoter. Intranasal administration of pCG nanoparticles resulted in evidence of transfection of brain cells, as shown both qualitatively, by GFP-immunohistochemistry, and quantitatively, by GFP-ELISA. Expression was detected throughout the rat brain two days post-administration. Following the proof

  4. Intranasal Flu Vaccine Protective against Seasonal and H5N1 Avian Influenza Infections

    Science.gov (United States)

    Alsharifi, Mohammed; Lobigs, Mario; Koskinen, Aulikki; Regner, Matthias; Trinidad, Lee; Boyle, David B.; Müllbacher, Arno

    2009-01-01

    Background Influenza A (flu) virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between virus strains. We have previously reported that γ-ray inactivated flu virus can induce cross-reactive Tc cell responses. Methodology/Principal Finding Here, we report that intranasal administration of purified γ-ray inactivated human influenza A virus preparations (γ-Flu) effectively induces heterotypic and cross-protective immunity. A single intranasal administration of γ-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections. Conclusions/Significance Intranasal γ-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections. PMID:19401775

  5. Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections.

    Directory of Open Access Journals (Sweden)

    Mohammed Alsharifi

    Full Text Available BACKGROUND: Influenza A (flu virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc cell responses, which are broadly cross-reactive between virus strains. We have previously reported that gamma-ray inactivated flu virus can induce cross-reactive Tc cell responses. METHODOLOGY/PRINCIPAL FINDING: Here, we report that intranasal administration of purified gamma-ray inactivated human influenza A virus preparations (gamma-Flu effectively induces heterotypic and cross-protective immunity. A single intranasal administration of gamma-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections. CONCLUSIONS/SIGNIFICANCE: Intranasal gamma-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections.

  6. [Targeting the brain through the nose. Effects of intranasally administered insulin].

    Science.gov (United States)

    Brünner, Y F; Benedict, C; Freiherr, J

    2013-08-01

    The assumption that the human brain is an insulin-independent organ was disproved with the discovery of insulin receptors in the central nervous system in the year 1978. Evidence has been provided for a high density of insulin receptors in brain regions responsible for cognitive memory processes (hippocampus) and for the regulation of appetite (hypothalamus). Accordingly, in animal studies an increased insulin level in the central nervous system leads to an improvement of hippocampal memory function and a decrease of food intake. Similar results were obtained in humans using the method of intranasal administration of insulin. Intranasal insulin reaches the brain and the cerebrospinal fluid via the olfactory epithelium and olfactory nerve fiber bundles leading through the lamina cribrosa to the olfactory bulb. Thus, this method renders the investigation of specific insulin effects in humans possible. The therapeutic potential of an intranasal insulin administration for the treatment of diseases for which an imbalance of the central nervous insulin metabolism is discussed (e.g. Alzheimer's disease, diabetes mellitus and obesity) can only be estimated with the help of further clinical studies. PMID:23760596

  7. Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting.

    Science.gov (United States)

    Mahajan, Hitendra S; Mahajan, Milind S; Nerkar, Pankaj P; Agrawal, Anshuman

    2014-03-01

    The central nervous system (CNS) is an immunological privileged sanctuary site-providing reservoir for HIV-1 virus. Current anti-HIV drugs, although effective in reducing plasma viral levels, cannot eradicate the virus completely from the body. The low permeability of anti-HIV drugs across the blood-brain barrier (BBB) leads to insufficient delivery. Therefore, developing a novel approaches enhancing the CNS delivery of anti-HIV drugs are required for the treatment of neuro-AIDS. The aim of this study was to develop intranasal nanoemulsion (NE) for enhanced bioavailability and CNS targeting of saquinavir mesylate (SQVM). SQVM is a protease inhibitor which is a poorly soluble drug widely used as antiretroviral drug, with oral bioavailability is about 4%. The spontaneous emulsification method was used to prepare drug-loaded o/w nanoemulsion, which was characterized by droplet size, zeta potential, pH, drug content. Moreover, ex-vivo permeation studies were performed using sheep nasal mucosa. The optimized NE showed a significant increase in drug permeation rate compared to the plain drug suspension (PDS). Cilia toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVM-loaded NE. Results of in vivo biodistribution studies show higher drug concentration in brain after intranasal administration of NE than intravenous delivered PDS. The higher percentage of drug targeting efficiency (% DTE) and nose-to-brain drug direct transport percentage (% DTP) for optimized NE indicated effective CNS targeting of SQVM via intranasal route. Gamma scintigraphy imaging of the rat brain conclusively demonstrated transport of drug in the CNS at larger extent after intranasal administration as NE.

  8. In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain.

    Science.gov (United States)

    Liu, Qingfeng; Shao, Xiayan; Chen, Jie; Shen, Yehong; Feng, Chengcheng; Gao, Xiaoling; Zhao, Yue; Li, Jingwei; Zhang, Qizhi; Jiang, Xinguo

    2011-02-15

    Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-α level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain.

  9. Development of risperidone liposomes for brain targeting through intranasal route.

    Science.gov (United States)

    Narayan, Reema; Singh, Mohan; Ranjan, OmPrakash; Nayak, Yogendra; Garg, Sanjay; Shavi, Gopal V; Nayak, Usha Y

    2016-10-15

    The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential. PMID:27593571

  10. Early intervention with intranasal NPY prevents single prolonged stress-triggered impairments in hypothalamus and ventral hippocampus in male rats.

    Science.gov (United States)

    Laukova, Marcela; Alaluf, Lishay G; Serova, Lidia I; Arango, Victoria; Sabban, Esther L

    2014-10-01

    Intranasal administration of neuropeptide Y (NPY) is a promising treatment strategy to reduce traumatic stress-induced neuropsychiatric symptoms of posttraumatic stress disorder (PTSD). We evaluated the potential of intranasal NPY to prevent dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, a core neuroendocrine feature of PTSD. Rats were exposed to single prolonged stress (SPS), a PTSD animal model, and infused intranasally with vehicle or NPY immediately after SPS stressors. After 7 days undisturbed, hypothalamus and hippocampus, 2 structures regulating the HPA axis activity, were examined for changes in glucocorticoid receptor (GR) and CRH expression. Plasma ACTH and corticosterone, and hypothalamic CRH mRNA, were significantly higher in the vehicle but not NPY-treated group, compared with unstressed controls. Although total GR levels were not altered in hypothalamus, a significant decrease of GR phosphorylated on Ser232 and increased FK506-binding protein 5 mRNA were observed with the vehicle but not in animals infused with intranasal NPY. In contrast, in the ventral hippocampus, only vehicle-treated animals demonstrated elevated GR protein expression and increased GR phosphorylation on Ser232, specifically in the nuclear fraction. Additionally, SPS-induced increase of CRH mRNA in the ventral hippocampus was accompanied by apparent decrease of CRH peptide particularly in the CA3 subfield, both prevented by NPY. The results show that early intervention with intranasal NPY can prevent traumatic stress-triggered dysregulation of the HPA axis likely by restoring HPA axis proper negative feedback inhibition via GR. Thus, intranasal NPY has a potential as a noninvasive therapy to prevent negative effects of traumatic stress.

  11. Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

    Science.gov (United States)

    El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

    2016-09-20

    Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route. PMID:27154259

  12. Optimization of combinational intranasal drug delivery system for the management of migraine by using statistical design.

    Science.gov (United States)

    Kumar, Animesh; Garg, Tarun; Sarma, Ganti S; Rath, Goutam; Goyal, Amit Kumar

    2015-04-01

    Migraine is a chronic disorder characterized by significant headache and various associated symptoms which worsen with exertion. Zolmitriptan approved for use in the acute treatment of migraine and related vascular headaches but are limited by high pain recurrence due to rapid drug elimination. Combinationalformulationof triptans and a nonsteroidal anti-inflammatory drug may provide a quicker and longer duration of relief from the subsequent pain during the attack. In this study, we formulate a Zolmitriptan (ZT) & ketorolac tromethamine (KT) loaded thermo reversible in-situ mucoadhesive intranasal gel (TMISG) formulation which gels at the nasal mucosal temperature and contains a bioadhesive polymer (Xyloglucan) that lengthens the residence time will enhance the bioavailability of the combinational drugs. This study uses Box-Behnken design for the first time to develop, optimize the TMISG and assess factors affecting the critical quality attributes. Histopathological study of the nasal mucosa suggested that the formulation was safe for nasal administration. The statistical difference in absolute bioavailability between oral and intranasal route suggested that intranasal route had almost 21% increases in bioavailability for ZT and for KT there was 16% increase over oral formulations. Optimized formulation would help mitigate migraine associated symptoms much better over the currently available formulations.

  13. Anatomical and histological factors affecting intranasal drug and vaccine delivery.

    Science.gov (United States)

    Gizurarson, Sveinbjörn

    2012-11-01

    The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine delivery as well as the development of new devices. The surface area of the nasal cavity is about 160 cm2, or 96 m2 if the microvilli are included. The olfactory region, however, is only about 5 cm2 (0.3 m2 including the microvilli). There are 6 arterial branches that serve the nasal cavity, making this region a very attractive route for drug administration. The blood flow into the nasal region is slightly more than reabsorbed back into the nasal veins, but the excess will drain into the lymph vessels, making this region a very attractive route for vaccine delivery. Many of the side effects seen following intranasal administration are caused by some of the 6 nerves that serve the nasal cavity. The 5th cranial nerve (trigeminus nerve) is responsible for sensing pain and irritation following nasal administration but the 7th cranial nerve (facial nerve) will respond to such irritation by stimulating glands and cause facial expressions in the subject. The first cranial nerve (olfactory nerve), however, is the target when direct absorption into the brain is the goal, since this is the only site in our body where the central nervous system is directly expressed on the mucosal surface. The nasal mucosa contains 7 cell types and 4 types of glands. Four types of cells and 2 types of glands are located in the respiratory region but 6 cell types and 2 types of glands are found in the olfactory region. PMID:22788696

  14. Promnestic effects of intranasally applied pregnenolone in rats.

    Science.gov (United States)

    Abdel-Hafiz, Laila; Chao, Owen Y; Huston, Joseph P; Nikolaus, Susanne; Spieler, Richard E; de Souza Silva, Maria A; Mattern, Claudia

    2016-09-01

    The neurosteroid pregnenolone (PREG) has been shown to have memory-enhancing and anti-depressant action. The present study addresses the question of whether intranasally applied pregnenolone (IN-PREG) also has promnestic properties in the rat. We examined the effects of IN-PREG at doses of 0.187 and 0.373mg/kg on memory for objects and their location on learning and retention of escape in a water maze, and on behavior on the elevated plus maze. The main findings were: (a) Pre-trial, but not post-trial, administration of IN-PREG facilitated long-term memory in a novel object-preference test and a novel object-location preference test when tested 48h after dosing. (b) Over the duration of 5days of extinction trials, after learning to escape onto a hidden platform in a water maze, the animals treated with IN-PREG spent more time in searching for the absent platform, indicating either, or both, superior memory for the former position of the escape platform, or a higher resistance to extinction. (c) Administration of the anticholinergic, scopolamine, disrupted learning to escape from the water maze in the vehicle-treated group. The IN-PREG treated groups exhibited superior escape learning in comparison with vehicle controls, indicating that the treatment countered the scopolamine effect. IN-PREG treatment had no influence on behaviors on the elevated plus maze. Our results demonstrate that IN-PREG is behaviorally active with cognitive enhancing properties comparable to those known from studies employing systemic PREG administration. PMID:27423520

  15. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Science.gov (United States)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  16. Influenza (Flu) vaccine (Live, Intranasal): What you need to know

    Science.gov (United States)

    ... entirety from the CDC Inactivated Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... 1. Why get vaccinated? Influenza ("flu") is a contagious disease ... every year, usually between October and May. Flu is caused by ...

  17. Intranasal Immunization with Chitosan/pCAGGS-flaA Nanoparticles Inhibits Campylobacter jejuni in a White Leghorn Model

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    Jin-lin Huang

    2010-01-01

    Full Text Available Campylobacter jejuni is the most common zoonotic bacterium associated with human diarrhea, and chickens are considered to be one of the most important sources for human infection, with no effective prophylactic treatment available. We describe here a prophylactic strategy using chitosan-DNA intranasal immunization to induce specific immune responses. The chitosan used for intranasal administration is a natural mucus absorption enhancer, which results in transgenic DNA expression in chicken nasopharynx. Chickens immunized with chitosan-DNA nanoparticles, which carried a gene for the major structural protein FlaA, produced significantly increased levels of serum anti-Campylobacter jejuni IgG and intestinal mucosal antibody (IgA, compared to those treated with chitosan-DNA (pCAGGS. Chitosan-pCAGGS-flaA intranasal immunization induced reductions of bacterial expellation by 2-3 log10 and 2 log10 in large intestine and cecum of chickens, respectively, when administered with the isolated C. jejuni strain. This study demonstrated that intranasal delivery of chitosan-DNA vaccine successfully induced effective immune response and might be a promising vaccine candidate against C. jejuni infection.

  18. ENHANCED BIOAVAILABILITY OF DRUGS VIA INTRANASAL DRUG DELIVEY SYSTEM

    OpenAIRE

    kumar Brajesh; Shafat Kausar; Akhtar Ali; Prajapati S.K; Singh Devendra

    2012-01-01

    The aim of present investigation is to explain the enhancement of bioavailability of drug through intranasal drug delivery system. Intranasal Therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. This has been attributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled with avoidance of hepatic first-pass elimination, ...

  19. Non-invasive intranasal delivery of quetiapine fumarate loaded microemulsion for brain targeting: Formulation, physicochemical and pharmacokinetic consideration.

    Science.gov (United States)

    Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

    2016-08-25

    Systemic drug delivery in schizophrenia is a major challenge due to presence of obstacles like, blood-brain barrier and P-glycoprotein, which prohibit entry of drugs into the brain. Quetiapine fumarate (QF), a substrate to P-glycoprotein under goes extensive first pass metabolism leading to limited absorption thus necessitating frequent oral administration. The aim of this study was to develop QF based microemulsion (ME) with and without chitosan (CH) to investigate its potential use in improving the bioavailability and brain targeting efficiency following non-invasive intranasal administration. QF loaded ME and mucoadhesive ME (MME) showed globule size, pH and viscosity in the range of 29-47nm, 5.5-6.5 and 17-40cP respectively. CH-ME with spherical globules having mean size of 35.31±1.71nm, pH value of 5.61±0.16 showed highest ex-vivo nasal diffusion (78.26±3.29%) in 8h with no sign of structural damage upon histopathological examination. Circular plume with an ovality ratio closer to 1.3 for CH-ME depicted ideal spray pattern. Significantly higher brain/blood ratio of CH-ME in comparison to QF-ME and drug solution following intranasal administration revealed prolonged retention of QF at site of action suggesting superiority of CH as permeability enhancer. Following intranasal administration, 2.7 and 3.8 folds higher nasal bioavailability in brain with CH-ME compared to QF-ME and drug solution respectively is indicative of preferential nose to brain transport (80.51±6.46%) bypassing blood-brain barrier. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery. PMID:27174656

  20. MIDAZOLAM SEDATION IN PAEDIATRICS: COMPARATIVE STUDY OF INTRANASAL VERSUS SUBLINGUAL MIDAZOLAM ATOMIZER SPRAY IN PAEDIATRIC PATIENTS UNDERGOING MAGNETIC RESONANCE IMAGING

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    Santhisree

    2014-05-01

    Full Text Available INTRODUCTION: Magnetic Resonance Imaging (MRI causes a great amount of anxiety to both parents and child. Fear of unpleasant procedures and separation from parents may result in lasting and untoward psychological consequences in children. So sedation and anxiolysis is required for children undergoing even for minor diagnostic procedures. OBJECTIVES: The objectives of our study was to compare safety, onset of sedation, degree of sedation produced by intranasal and sublingual administration of midazolam for premedication in children of 4-10 years undergoing MRI. MATERIALS AND METHODS: In this prospective randomized double blind study, the intranasal and sublingual administration of midazolam in pediatric patients who were to undergo MRI was evaluated in 60 children who were aged between 4-10 years with ASA physical status I and II by using a newer midazolam spray. The patients were divided into two groups of 30 patients each and they received Midazolam 0.3 mg/kg. Either intranasally or sublingually in a randomized manner. The heart rate, oxygen saturation (SPO2, respiratory rate and the degree of sedation before and at 3 minutes intervals, recovery score, MRI image quality were recorded and compared. RESULTS: The respiratory rate, heart rate and the oxygen saturation was found from the baseline in both the groups (p >0.05. A sedation score of >3 (approx. was achieved in both the groups within 10 minutes of drug administration. The recovery score did not differ significantly between the two groups (p >0.05. CONCLUSION: Both the intranasal and sublingual administration of Midazolam as sedative is safe and equally effective in pediatric patients.

  1. The Efficacy of Intranasal Desmopressin as an Adjuvant in the Acute Renal Colic Pain Management

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    Kambiz Masoumi

    2014-01-01

    Full Text Available The aim of this study was to compare analgesic effect of intramuscular (IM sodium diclofenac and intranasal desmopressin combination with IM sodium diclofenac alone in patients with acute renal colic. In this randomized double-blind clinical trial, all patients aged 18 to 55 years who were diagnosed as acute renal colic and met the inclusion and exclusion criteria were randomized into two groups to receive 40 μg intranasal desmopressin spray and 75 mg IM sodium diclofenac combination (Group A or 75 mg IM sodium diclofenac alone (Group B. The pain score of patients was assessed using a visual analogue scale (VAS at baseline, 15, 30, 45, and 60 minutes after administration. Of all 159 patients who were assessed for eligibility finally, the results of 120 patients were analyzed. There was no significant difference regarding age and gender between two groups. The baseline VAS score was not significantly different between two groups (P=0.44. The Mean ± SD scores of two groups reduced 15 minutes after drug administration, but this decrease was significantly more in Group A compared with Group B (P=0.02. This pattern continued in minutes 30, 45, and 60 of drug administration. Our results showed that desmopressin could be used as an effective adjuvant in acute renal colic pain management.

  2. Immunogenicity and protective efficacy of an elastase-dependent live attenuated swine influenza virus vaccine administered intranasally in pigs.

    Science.gov (United States)

    Masic, Aleksandar; Lu, Xinya; Li, Junwei; Mutwiri, George K; Babiuk, Lorne A; Brown, Earl G; Zhou, Yan

    2010-10-01

    Influenza A virus is an important respiratory pathogen of swine that causes significant morbidity and economic impact on the swine industry. Vaccination is the first choice for prevention and control of influenza infections. Live attenuated influenza vaccines (LAIV) are approved for use in humans and horses and their application provides broad protective immunity, however no LAIV against swine influenza virus (SIV) exists in the market. Previously we reported that an elastase-dependent mutant SIV A/Sw/Sk-R345V (R345V) derived from A/Sw/Saskatchewan/18789/02 (H1N1) (SIV/Sk02) is highly attenuated in pigs. Two intratracheal administrations of R345V induced strong cell-mediated and humoral immune responses and provided a high degree of protection to antigenically different SIV infection in pigs. Here we evaluated the immunogenicity and the protective efficacy of R345V against SIV infection by intranasal administration, the more practical route for vaccination of pigs in the field. Our data showed that intranasally administered R345V live vaccine is capable of inducing strong antigen-specific IFN-γ response from local tracheo-bronchial lymphocytes and antibody responses in serum and respiratory mucosa after two applications. Intranasal vaccination of R345V provided pigs with complete protection not only from parental wild type virus infection, but also from homologous antigenic variant A/Sw/Indiana/1726/88 (H1N1) infection. Moreover, intranasal administration of R345V conferred partial protection from heterologous subtypic H3N2 SIV infection in pigs. Thus, R345V elastase-dependent mutant SIV can serve as a live vaccine against antigenically different swine influenza viruses in pigs.

  3. Immunogenicity and protective efficacy of an elastase-dependent live attenuated swine influenza virus vaccine administered intranasally in pigs.

    Science.gov (United States)

    Masic, Aleksandar; Lu, Xinya; Li, Junwei; Mutwiri, George K; Babiuk, Lorne A; Brown, Earl G; Zhou, Yan

    2010-10-01

    Influenza A virus is an important respiratory pathogen of swine that causes significant morbidity and economic impact on the swine industry. Vaccination is the first choice for prevention and control of influenza infections. Live attenuated influenza vaccines (LAIV) are approved for use in humans and horses and their application provides broad protective immunity, however no LAIV against swine influenza virus (SIV) exists in the market. Previously we reported that an elastase-dependent mutant SIV A/Sw/Sk-R345V (R345V) derived from A/Sw/Saskatchewan/18789/02 (H1N1) (SIV/Sk02) is highly attenuated in pigs. Two intratracheal administrations of R345V induced strong cell-mediated and humoral immune responses and provided a high degree of protection to antigenically different SIV infection in pigs. Here we evaluated the immunogenicity and the protective efficacy of R345V against SIV infection by intranasal administration, the more practical route for vaccination of pigs in the field. Our data showed that intranasally administered R345V live vaccine is capable of inducing strong antigen-specific IFN-γ response from local tracheo-bronchial lymphocytes and antibody responses in serum and respiratory mucosa after two applications. Intranasal vaccination of R345V provided pigs with complete protection not only from parental wild type virus infection, but also from homologous antigenic variant A/Sw/Indiana/1726/88 (H1N1) infection. Moreover, intranasal administration of R345V conferred partial protection from heterologous subtypic H3N2 SIV infection in pigs. Thus, R345V elastase-dependent mutant SIV can serve as a live vaccine against antigenically different swine influenza viruses in pigs. PMID:20708697

  4. Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone

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    Xu Gelin

    2008-12-01

    Full Text Available Abstract Background The effect of neurotrophic factors in enhancing stroke-induced neurogenesis in the adult subventricular zone (SVZ is limited by their poor blood-brain barrier (BBB permeability. Intranasal administration is a noninvasive and valid method for delivery of neuropeptides into the brain, to bypass the BBB. We investigated the effect of treatment with intranasal transforming growth factor-β1 (TGF-β1 on neurogenesis in the adult mouse SVZ following focal ischemia. The modified Neurological Severity Scores (NSS test was used to evaluate neurological function, and infarct volumes were determined from hematoxylin-stained sections. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL labeling was performed at 7 days after middle cerebral artery occlusion (MCAO. Immunohistochemistry was used to detect bromodeoxyuridine (BrdU and neuron- or glia-specific markers for identifying neurogenesis in the SVZ at 7, 14, 21, 28 days after MCAO. Results Intranasal treatment of TGF-β1 shows significant improvement in neurological function and reduction of infarct volume compared with control animals. TGF-β1 treated mice had significantly less TUNEL-positive cells in the ipsilateral striatum than that in control groups. The number of BrdU-incorporated cells in the SVZ and striatum was significantly increased in the TGF-β1 treated group compared with control animals at each time point. In addition, numbers of BrdU- labeled cells coexpressed with the migrating neuroblast marker doublecortin (DCX and the mature neuronal marker neuronal nuclei (NeuN were significantly increased after intranasal delivery of TGF-β1, while only a few BrdU labeled cells co-stained with glial fibrillary acidic protein (GFAP. Conclusion Intranasal administration of TGF-β1 reduces infarct volume, improves functional recovery and enhances neurogenesis in mice after stroke. Intranasal TGF-β1 may have therapeutic potential for cerebrovascular

  5. Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

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    Yingying Xu

    2014-07-01

    Full Text Available Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT. Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.

  6. Food consumption and activity levels increase in rats following intranasal Hypocretin-1.

    Science.gov (United States)

    Dhuria, Shyeilla V; Fine, Jared M; Bingham, Deborah; Svitak, Aleta L; Burns, Rachel B; Baillargeon, Amanda M; Panter, Scott S; Kazi, Abdul N; Frey, William H; Hanson, Leah R

    2016-08-01

    Hypocretin-1 (HC, orexin-A) is a neuropeptide involved in regulating physiological functions of sleep, appetite and arousal, and it has been shown that intranasal (IN) administration can target HC to the brain. Recent clinical studies have shown that IN HC has functional effects in human clinical trials. In this study, we use rats to determine whether IN HC has an immediate effect on food consumption and locomotor activity, whether distribution in the brain after IN delivery is dose-dependent, and whether MAPK and PDK1 are affected after IN delivery. Food intake and wheel-running activity were quantified for 24h after IN delivery. Biodistribution was determined 30min after IN delivery of both a high and low dose of 125I-radiolabelled HC throughout the brain and other bodily tissues, while Western blots were used to quantify changes in cell signaling pathways (MAPK and PDK1) in the brain. Intranasal HC significantly increased food intake and wheel activity within 4h after delivery, but balanced out over the course of 24h. The distribution studies showed dose-dependent delivery in the CNS and peripheral tissues, while PDK1 was significantly increased in the brain 30min after IN delivery of HC. This study adds to the growing body of evidence that IN administration of HC is a promising strategy for treatment of HC related behaviors. PMID:27264485

  7. ENHANCED BIOAVAILABILITY OF DRUGS VIA INTRANASAL DRUG DELIVEY SYSTEM

    Directory of Open Access Journals (Sweden)

    kumar Brajesh

    2012-07-01

    Full Text Available The aim of present investigation is to explain the enhancement of bioavailability of drug through intranasal drug delivery system. Intranasal Therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. This has been attributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled with avoidance of hepatic first-pass elimination, gut wall metabolism and/or destruction in the gastrointestinal tract. Intranasal microemulsion, gels, nanoparticles, liposome and microspheres have gained increased interest in recent years as a delivery system for protein and peptides through the nasal route. Thus this review focuses on nasal drug delivery, nasal drug absorption mechanisms, various mechanisms for increasing the bioavailability of drug, and their applications in drug delivery.

  8. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis

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    Greiff Lennart

    2012-06-01

    Full Text Available Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779. In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003. Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.

  9. Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression.

    Science.gov (United States)

    Haque, Shadabul; Md, Shadab; Sahni, Jasjeet Kaur; Ali, Javed; Baboota, Sanjula

    2014-01-01

    The purpose of the present study was to investigate the potential of Venlafaxine loaded alginate nanoparticles (VLF AG-NPs) for treatment of depression via intranasal (i.n.) nose to brain delivery route. The VLF AG-NPs were prepared and optimized on the basis of various physio-chemical characteristics. Pharmacodynamic studies of the VLF AG-NPs for antidepressant activity were carried in-vivo by forced swimming test and locomotor activity test on albino Wistar rats. VLF AG-NPsi.n. treatment significantly improved the behavioural analysis parameters i.e. swimming, climbing, and immobility in comparison to the VLF solutioni.n. and VLF tabletoral. The intranasal VLF AG-NPs also improved locomotor activity when compared with VLF solutioni.n. and VLF tabletoral. Confocal laser scanning fluorescence microscopy studies were performed on isolated organs of rats after intravenous and intranasal administrations of Rodamine-123 loaded alginate nanoparticles to determine its efficacy for nose to brain delivery and also for its qualitative distribution to other organs. Brain uptake and pharmacokinetic studies were performed by determination of VLF concentration in blood and brain respectively for VLF AG-NPsi.n., VLF solutioni.n. and VLF solutioni.v. The greater brain/blood ratios for VLF AG-NPsi.n. in comparison to VLF solutioni.n. and VLF solutioni.v. respectively at 30 min are indicative of superiority of alginate nanoparticles for direct nose to brain transport of VLF. Thus, VLF AG-NPsi.n. delivered greater VLF to the brain in comparison to VLF solution which indicates that VLF AG-NPs could be a promising approach for the treatment of depression.

  10. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

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    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

  11. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Mott, Brittney [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States); Thamake, Sanjay [Radio-Isotope Therapy of America Foundation (United States); Vishwanatha, Jamboor; Jones, Harlan P., E-mail: harlan.jones@unthsc.edu [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States)

    2013-05-15

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 {+-} 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-{gamma} cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  12. Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

    NARCIS (Netherlands)

    Verheul, R.J.

    2010-01-01

    Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need fo

  13. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

    Energy Technology Data Exchange (ETDEWEB)

    Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik [University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); Froehlich, Johannes M. [Klus-Apotheke, Zuerich (Switzerland)

    2007-06-15

    The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form. (orig.)

  14. Formulation, optimization and evaluation of spray-dried mucoadhesive microspheres as intranasal carriers for Valsartan.

    Science.gov (United States)

    Pardeshi, Chandrakant V; Rajput, Pravin V; Belgamwar, Veena S; Tekade, Avinash R

    2012-01-01

    This investigation deals with the intranasal delivery of Valsartan, encapsulated in HPMC-based spray-dried mucoadhesive microspheres, with an aim to provide rapid absorption and quick onset of action for treating hypertension. A 2³-factorial design has been employed for the assessment of influence of three independent variables, namely inlet temperature, feed-flow rate and drug-polymer ratio on production yield, particle size and in vitro drug diffusion of the prepared microspheres. Microspheres were evaluated for particle size, entrapment efficiency, swelling property, in vitro mucoadhesion, in vitro drug diffusion, ex vivo drug permeation, histopathological examination and stability studies. The results of differential scanning calorimetry, X-ray diffraction and scanning electron microscopy revealed molecular dispersion of Valsartan into microspheres with spherical shape and smooth surface. Optimized formulation indicated good mucoadhesion with no severe sign of damage on nasal mucosa. Results of the non-invasive animal studies in dexamethasone-induced hypertensive rat model suggested the suitability of investigated drug delivery system for intranasal administration.

  15. Formulation and optimization of mucoadhesive microemulsion containing mirtazapine for intranasal delivery

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    Hetal P Thakkar

    2014-01-01

    Full Text Available Background: Mirtazapine, an antidepressant drug, has absolute bioavailability of only 50% due to high first pass metabolism. Aim: The purpose of this study was to develop and optimize mucoadhesive microemulsion containing mirtazapine for intranasal delivery. Materials and Methods: Based on solubility study, Capmul Medium chain Monoglyceride, Tween 80 and polyethylene glycol (PEG 400 were selected as oil, surfactant and co surfactant respectively. Microemulsions were prepared using water titration method. 3:1% w/w ratio (Tween 80: PEG 400 was selected for formulation development. The prepared microemulsions were optimized for globule size, zeta potential, % transmittance and polydispersity index. The optimized batch was further characterized for % drug content, conductivity and transmission electron microscopy. Results and Conclusion: All the parameters showed the suitability of microemulsion of mirtazapine for intranasal delivery. Chitosan (0.5% w/w was used as a polymer for the preparation of mucoadhesive microemulsion to enhance the retention time in the nasal mucosa. Results of nasal toxicity study using excised sheep nasal mucosa showed comparatively no damage to epithelium and so formulation was considered safe for nasal administration. mirtazapine mucoadhesive microemulsion showed the highest percentage of diffusion (57.11 ± 0.710% after 210 min during in-vitro drug diffusion study through sheep nasal mucosa, followed by mirtazapine microemulsion (46.08 ± 0.674% and finally by mirtazapine solution (17.63 ± 0.612%.

  16. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

    Science.gov (United States)

    Muntimadugu, Eameema; Dhommati, Raju; Jain, Anjali; Challa, Venu Gopala Swami; Shaheen, M; Khan, Wahid

    2016-09-20

    Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. PMID:27185298

  17. Nanogel-based PspA intranasal vaccine prevents invasive disease and nasal colonization by Streptococcus pneumoniae.

    Science.gov (United States)

    Kong, Il Gyu; Sato, Ayuko; Yuki, Yoshikazu; Nochi, Tomonori; Takahashi, Haruko; Sawada, Shinichi; Mejima, Mio; Kurokawa, Shiho; Okada, Kazunari; Sato, Shintaro; Briles, David E; Kunisawa, Jun; Inoue, Yusuke; Yamamoto, Masafumi; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2013-05-01

    To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection. PMID:23460513

  18. EVALUATION OF EFFICACY OF INTRANASAL MIDAZOLAM SPRA Y FOR PREANAESTHETIC MEDICATION IN PAEDIATRIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Sneha P.

    2013-05-01

    Full Text Available ABSTRACT: BACKGROUND: Preoperative anxiety and long-term behavioural pro blems are inevitable consequences in absence of preoperative sedation in paediatric patients undergoing surgery. An ideal premedicant removes fear and anxi ety in tender minds of children and achieves a calm, sedated child for smooth induction of anaesth esia and rapid recovery in postoperative period. Midazolam is the most commonly used premedicant in children as it satisfies most of the criteria of ideal premedicant but its route of administration i s a debatable issue in anaesthesia practice. AIMS: This study evaluated the efficacy of atomized intra nasal midazolam spray as a painless, user- friendly, needleless system of drug administration for pre-anaesthetic medication in paediatric patients. SETTINGS AND DESIGN: Tertiary hospital, a prospective, randomized, cont rolled, clinical study. METHODS AND MATERIAL: 60 ASA physical status I children of 2-5 years age group, weighing 10-18 kg scheduled for routine surgeries p articipated in the study. Children were randomly assigned to Group M: Received intranasal m idazolam spray in doses of 0.2 mg/kg and Group N: Received normal saline drops (1-2 drops/no stril. Patients were observed in preoperative room for 20 min. Acceptance of drug, response to dr ug administration, sedation scale, separation score, acceptance to mask, recovery score and side effects of drug were noted. STATISTICAL ANALYSIS: Student ‘t’ test, standard error of difference bet ween two means and Chi-square test. p value0.05. 20 min after p remedication 76.66% in group M and 10.00% group N, children showed satisfactory sedation (p<0 .05. 73.33% in group M while 26.66% in group N, children showed acceptable parental separa tion and 86.66% in group M while 23.33% group N, children showed satisfactory acceptance to mask (p<0.05. Transient nasal irritation in the form of rubbing of nose, watering, sneezing and lac rimation was observed in 40% children of

  19. Evaluation of Intranasal Midazolam as an Anesthetic Premedication in Preschool Children

    Directory of Open Access Journals (Sweden)

    Sh Behdad

    2005-10-01

    Full Text Available Introduction: Preoperative psycho emotional preparation of patients is one of the principle purposes of anesthesia which can be achieved by administration of premedications. Children should receive premedication before entering the operating room due to their dependence on parents and the fear and anxiety of separation from parents. Different drugs are administered for this purpose, but considering children's sensitivity, it is wise to use the most effective and comfortable medication with least side effects. Midazolam is a rapid onset, short acting and water soluble benzodiazapine which can be administered by oral, intravenous, intramuscular, rectal or intranasal routes. The purpose of this study was to evaluate the result of intranasal midazolam administration (0.2 mg/kg as a premedication in children aged 2-6 years.( Min dose and enough time Methods: In this randomized prospective study, 100 children aged between 2-6 years old in class ASA 1 and candidates of surgery were divided into two groups; case and control. The control group received several nasal drops of normal saline, while the case group received 0.2 mg/kg nasal midazolam 20 minutes before anesthesia induction. Results: Twenty minutes after administration of the nasal drops, 14% in the control group and 68% in the case group were alert and calm. (P value=0.0 . Mask acceptance during induction of anesthesia in control and case group was 14%and 72%, respectively (P value >0.00 The recovery time in the case group was longer (P value >0.5, but no complications (nausea, vomiting, respiratory and cardiovascular problems were seen in either group. Conclusion: Nasal midazolam with its anxiolytic, tranquilizing effects and no respiratory or cardiovascular complications is a safe drug and being better than parenteral drugs is acceptable by children.

  20. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

    Science.gov (United States)

    Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

    2016-06-01

    The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

  1. A new brain drug delivery strategy: focused ultrasound-enhanced intranasal drug delivery.

    Science.gov (United States)

    Chen, Hong; Chen, Cherry C; Acosta, Camilo; Wu, Shih-Ying; Sun, Tao; Konofagou, Elisa E

    2014-01-01

    Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (i.n.) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+i.n.) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After i.n. administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (i.v.) drug injection is employed, FUS was also applied after i.v. injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+i.n. enhanced drug delivery within the targeted region compared with that achieved by i.n. only. Despite the fact that the i.n. route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+i.n. was not significantly different from that of FUS+i.v.. As a new drug delivery platform, the FUS+i.n. technique is potentially useful for treating CNS diseases.

  2. Stimulus Selection for Intranasal Sensory Isolation: Eugenol Is an Irritant

    OpenAIRE

    Wise, Paul M.; Wysocki, Charles J.; Lundström, Johan N.

    2012-01-01

    Both the olfactory and the trigeminal systems are able to respond to intranasal presentations of chemical vapor. Accordingly, when the nose detects a volatile chemical, it is often unclear whether we smell it, feel it, or both. The distinction may often be unimportant in our everyday perception of fragrances or aromas, but it can matter in experiments that purport to isolate olfactory processes or study the interaction between olfaction and chemesthesis. Researchers turn to a small pool of co...

  3. Intranasal Delivery of NEMO-Binding Domain Peptide Prevents Memory Loss in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Rangasamy, Suresh B; Corbett, Grant T; Roy, Avik; Modi, Khushbu K; Bennett, David A; Mufson, Elliott J; Ghosh, Sankar; Pahan, Kalipada

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia. Despite intense investigations, no effective therapy is available to halt its progression. We found that NF-κB was activated within the hippocampus and cortex of AD subjects and that activated forms of NF-κB negatively correlated with cognitive function monitored by Mini-Mental State Examination and global cognitive z score. Accordingly, NF-κB activation was also observed in the hippocampus of a transgenic (5XFAD) mouse model of AD. It has been shown that peptides corresponding to the NF-κB essential modifier (NEMO)-binding domain (NBD) of IκB kinase α (IKKα) or IκB kinase β (IKKβ) specifically inhibit the induction of NF-κB activation without inhibiting the basal NF-κB activity. Interestingly, after intranasal administration, wild-type NBD peptide entered into the hippocampus, reduced hippocampal activation of NF-κB, suppressed hippocampal microglial activation, lowered the burden of Aβ in the hippocampus, attenuated apoptosis of hippocampal neurons, protected plasticity-related molecules, and improved memory and learning in 5XFAD mice. Mutated NBD peptide had no such protective effect, indicating the specificity of our finding. These results suggest that selective targeting of NF-κB activation by intranasal administration of NBD peptide may be of therapeutic benefit for AD patients. PMID:26401561

  4. Brief report: oxytocin enhances paternal sensitivity to a child with autism: a double-blind within-subject experiment with intranasally administered oxytocin.

    Science.gov (United States)

    Naber, Fabiënne B A; Poslawsky, Irina E; van Ijzendoorn, Marinus H; van Engeland, Herman; Bakermans-Kranenburg, Marian J

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is presented. Fathers with their typically developing toddler (n = 18), and fathers of toddlers diagnosed with ASD (n = 14), were observed in two play sessions of 15 min each with an intervening period of 1 week. In all fathers oxytocin elevated the quality of paternal sensitive play: fathers stimulated their child in a more optimal way, and they showed less hostility which suggests the positive effects of oxytocin on paternal sensitive play irrespective of clinical status of their child. PMID:22544470

  5. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    Science.gov (United States)

    2003-01-01

    submitting a licence application in Europe, a $US27.5 million payment for approval of a refrigerator-stable liquid formulation of FluMist and as much as $US50 million for licensing of FluMist internationally. In July 2003 MedImmune announced that it had received approximately $US28 million in milestone payments during Q2 of 2003 for the approval of FluMist. CSL Ltd of Australia will collaborate on the development, sale and distribution of MedImmune Vaccine's vaccine in Australia, New Zealand and certain countries in the South Pacific. MedImmune is to acquire vaccine research programmes in respiratory syncytial virus and cytomegalovirus from MedImmune Vaccines. The company's primary interest is in FluMist. In May 2002, MedImmune licensed exclusive rights to Crucell's proprietary human cell line PER.C6 for use in its influenza vaccine programmes. On 11 March 2002, American Home Products changed its name and the names of its subsidiaries Wyeth-Ayerst and Wyeth-Lederle to Wyeth. Wyeth's vaccines division is called Wyeth Vaccines. On 29 September 2000, Aviron announced that it had been awarded a $US2.7 million Challenge Grant from NIAID for development of vaccines against pandemic strains of influenza based on FluMist intranasal technology. The cold-adapted live influenza vaccine has been widely evaluated in the US and Japan since 1975 in clinical trials involving several thousand people. Aviron completed phase II clinical trials in adults in the US and phase III trials in US children aged 15-71 months. Additional phase III trials in adults and the elderly are ongoing. Aviron also commenced phase III trials to test the safety of its intranasal live vaccine in children with moderate to severe asthma. The vaccine is delivered using the AccuSpray nasal delivery system by Becton Dickinson, which will supply the system for FluMist through the 2001-2002 influenza season under an agreement with Aviron made in August 1998. On 7 March 2000, Aviron announced that Wyeth-Lederle Vaccines

  6. The diagnostic contribution of computed tomography in intranasal carcinoma with retrobulbar, oral and brain invasion in a canine: case report; Contribuicao da tomografia computadorizada no diagnostico de carcinoma intranasal com invasao retrobular, oral e cerebral em canino: relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Zardo, Karen Maciel, E-mail: kmz@bol.com.br; Belotta, Alexandra Frey; Babicsak, Viviam Rocco; Machado, Vania Maria de Vasconcelos [Universidade Estadual Paulista Julio de Mesquita Filho (FMVZ/UNESP), Botucatu, SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia. Dept. de Reproducao Animal e Radiologia Veterinaria; Zanoni, Diogo Souza; Costa, Denis Carvalho [Universidade Estadual Paulista Julio de Mesquita Filho (FMVZ/UNESP), Botucatu, SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia. Dept. de Clinica Veterinaria

    2012-07-01

    Intranasal tumors are uncommon and in most cases are malignant, aggressive and with low to moderate potential for metastasis. Clinical signs are usually caused by progressive obstruction of the upper airways. The test cytopathological also is a diagnosis method, but the definitive diagnosis is made by histopathological. Computed tomography (CT) is recommended to treatment planning. A poodle was attended at the veterinary hospital with a clinical history of epistaxis and nasal and ocular secretions, seizures and severe dyspnoea. The animal underwent to radiographic examination of the chest and skull as well as helical computed tomography of the nasal cavity and brain before and after the administration of intravenous contrast. The CT findings revealed an expansive bilateral nasal cavity neoformation, with involvement of the retrobulbar space, right frontal sinus, brain and oral cavity, suggesting a neoplastic or an infectious process. The CT examination allowed the material collection, directly from the mass, to cytological examination, providing the diagnosis of carcinoma. CT also allowed the determination of the unfavorable prognosis of the patient and the treatment planning which not included the surgical excision of the neoformation. Although CT was not conclusive in the diagnosis of carcinoma, it was essential to accurately define the extent of the lesion, to guide the collection of material directly from the tumor and to determine the prognosis of the animal, proving to be an extremely useful tool in cases of tumors intranasal in dogs. (author)

  7. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Anagnostou Evdokia

    2012-12-01

    effects were reported. Conclusions This pilot study suggests that there is therapeutic potential to daily administration of intranasal oxytocin in adults with ASD and that larger and longer studies are warranted. Trial registration NCT00490802

  8. Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department

    Science.gov (United States)

    Reynolds, Stacy L; Studnek, Jonathan R; Bryant, Kathleen; VanderHave, Kelly; Grossman, Eric; Moore, Charity G; Young, James; Hogg, Melanie; Runyon, Michael S

    2016-01-01

    Introduction Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage. Methods and analysis This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 μg/kg) for analgesia in 80 children aged 4–17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug. Ethics and dissemination This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial. Trial registration number NCT02521415. PMID:27609854

  9. Intranasally administered oxytocin affects how dogs (Canis familiaris) react to the threatening approach of their owner and an unfamiliar experimenter.

    Science.gov (United States)

    Hernádi, Anna; Kis, Anna; Kanizsár, Orsolya; Tóth, Katinka; Miklósi, Bernadett; Topál, József

    2015-10-01

    Fear and aggression are among the most prominent behavioural problems in dogs. Oxytocin has been shown to play a role in regulating social behaviours in humans including fear and aggression. As intranasal oxytocin has been found to have some analogous effects in dogs and humans, here we investigated the effect of oxytocin on dogs' behaviour in the Threatening Approach Test. Dogs, after having received intranasal administration of oxytocin (OT) or placebo (PL), showed the same reaction to an unfamiliar experimenter, but OT pretreated dogs showed a less friendly first reaction compared to the PL group when the owner was approaching. Individual differences in aggression (measured via questionnaire) also modulated dogs' first reaction. Moreover, subjects that received OT looked back more at the human (owner/experimenter) standing behind them during the threatening approach. These results suggest that oxytocin has an effect on dogs' response to the threatening cues of a human, but this effect is in interaction with other factors such as the identity of the approaching human and the 'baseline' aggression of the dogs.

  10. Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM?

    Directory of Open Access Journals (Sweden)

    Stefaan W. van Gool

    2013-08-01

    Full Text Available Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy of classic therapeutic tools. Local administration methods of therapeutic agents, such as convection enhanced delivery and intracerebral injections, are often associated with adverse events. The intranasal pathway has been proposed as a non-invasive alternative route to deliver therapeutics to the brain. This route will bypass the blood-brain barrier and limit systemic side effects. Upon presentation at the nasal cavity, pharmacological agents reach the brain via the olfactory and trigeminal nerves. Recently, formulations have been developed to further enhance this nose-to-brain transport, mainly with the use of nanoparticles. In this review, the focus will be on formulations of pharmacological agents, which increase the nasal permeation of hydrophilic agents to the brain, improve delivery at a constant and slow release rate, protect therapeutics from degradation along the pathway, increase mucoadhesion, and facilitate overall nasal transport. A mounting body of evidence is accumulating that the underexplored intranasal delivery route might represent a major breakthrough to combat glioblastoma.

  11. The diagnostic contribution of computed tomography in intranasal carcinoma with retrobulbar, oral and brain invasion in a canine: case report

    International Nuclear Information System (INIS)

    Intranasal tumors are uncommon and in most cases are malignant, aggressive and with low to moderate potential for metastasis. Clinical signs are usually caused by progressive obstruction of the upper airways. The test cytopathological also is a diagnosis method, but the definitive diagnosis is made by histopathological. Computed tomography (CT) is recommended to treatment planning. A poodle was attended at the veterinary hospital with a clinical history of epistaxis and nasal and ocular secretions, seizures and severe dyspnoea. The animal underwent to radiographic examination of the chest and skull as well as helical computed tomography of the nasal cavity and brain before and after the administration of intravenous contrast. The CT findings revealed an expansive bilateral nasal cavity neoformation, with involvement of the retrobulbar space, right frontal sinus, brain and oral cavity, suggesting a neoplastic or an infectious process. The CT examination allowed the material collection, directly from the mass, to cytological examination, providing the diagnosis of carcinoma. CT also allowed the determination of the unfavorable prognosis of the patient and the treatment planning which not included the surgical excision of the neoformation. Although CT was not conclusive in the diagnosis of carcinoma, it was essential to accurately define the extent of the lesion, to guide the collection of material directly from the tumor and to determine the prognosis of the animal, proving to be an extremely useful tool in cases of tumors intranasal in dogs. (author)

  12. Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium

    Science.gov (United States)

    Kupke, Alexandra; Wenisch, Sabine; Failing, Klaus; Herden, Christiane

    2016-01-01

    The olfactory epithelium (OE) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., Borna disease virus, equine herpesvirus 1 (EHV-1), hendra virus, influenza virus, rabies virus, vesicular stomatitis virus can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines, or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g., horses would help to underscore transferability of rodent models. Analysis of the complete noses of five adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein and doublecortin (DCX) expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen and tropomyosin receptor kinase A was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine types a and b were located differently within the nose and

  13. A prospective randomized comparative study of the effects of intranasal and transdermal 17 β-estradiol on postmenopausal symptoms and vaginal cytology

    Directory of Open Access Journals (Sweden)

    Odabasi A

    2007-01-01

    Full Text Available Context: Investigating the adverse effects of oral hormone replacement therapy (HRT, the clinical effectiveness of alternative combinations and route of administrations. Aim: To compare the effects of intranasal and transdermal 17β-estradiol combined with vaginal progesterone on vasomotor symptoms and vaginal cytology. Settings and Design: A 12-week, prospective, randomized comparative study was conducted between July 2005 and September 2006. Materials and Methods: Eighty postmenopausal women aged between 42-57 years, who had scores of ≥1.7 on the menopause rating scale-I (MRS-I items "1-6", were randomly assigned to receive intranasal (300 µg/day, n =40 or transdermal (50 µg/day, n =40 17β-estradiol continuously. All patients also received a vaginal progesterone gel twice weekly. Vasomotor symptoms were evaluated at weeks 0, 4, 8 and 12. Vaginal maturation index (VMI was evaluated at weeks 0 and 12 of the study. Statistical Analyses: The Mann-Whitney U and the Wilcoxon tests were used. P < 0.05 was regarded as significant. Results: Thirty-two women in the intranasal and 29 women in the transdermal group completed the study. The total score of the MRS, the sum-scores of Factor 1 "HOT FLUSHES" and Factor 2 "PSYCHE" significantly decreased in both groups at week 4. Factor 3 "ATROPHY" scores significantly decreased only in the transdermal group at week 12. The VMI showed no changes within and between the two groups at the end of the study. Conclusion: Intranasal and transdermal 17β-estradiol combined with vaginal progesterone gel as a continuous HRT caused a similar decrease in vasomotor symptoms but did not have any significant effect on VMI after 12 weeks of treatment in this study population.

  14. Formulation and kinetic modeling of curcumin loaded intranasal mucoadhesive microemulsion

    Directory of Open Access Journals (Sweden)

    B Mikesh Patel

    2012-01-01

    Full Text Available It is a challenge to develop the optimum dosage form of poorly water-soluble drugs and to target them due to limited bioavailability, intra and inter subject variability. In this investigation, mucoadhesive microemulsion of curcumin was developed by water titration method taking biocompatible components for intranasal delivery and was characterized. Nasal ciliotoxicity studies were carried out using excised sheep nasal mucosa. in vitro release studies of formulations and PDS were performed. Labrafil M 1944 CS based microemulsion was transparent, stable and nasal non-ciliotoxic having particle size 12.32±0.81nm (PdI=0.223 and from kinetic modeling, the release was found to be Fickian diffusion for mucoadhesive microemulsion.

  15. Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide.

    Science.gov (United States)

    Shelke, Santosh; Shahi, Sadhana; Jadhav, Kiran; Dhamecha, Dinesh; Tiwari, Roshan; Patil, Hemlata

    2016-06-01

    The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability. PMID:27091045

  16. Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide.

    Science.gov (United States)

    Shelke, Santosh; Shahi, Sadhana; Jadhav, Kiran; Dhamecha, Dinesh; Tiwari, Roshan; Patil, Hemlata

    2016-06-01

    The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability.

  17. Solid lipid nanoparticles of ondansetron HCl for intranasal delivery: development, optimization and evaluation.

    Science.gov (United States)

    Joshi, Ashwini S; Patel, Hitesh S; Belgamwar, Veena S; Agrawal, Anshuman; Tekade, Avinash R

    2012-09-01

    The present investigation deals with the development and statistical optimization of solid lipid nanoparticles (SLNs) of ondansetron HCl (OND) for intranasal (i.n.) delivery. SLNs were prepared using the solvent diffusion technique and a 2(3) factorial design. The concentrations of lipid, surfactant and cosurfactant were independent variables in this design, whereas, particle size and entrapment efficiency (EE) were dependent variables. The particle size of the SLNs was found to be 320-498 nm, and the EE was between 32.89 and 56.56 %. The influence of the lipid, surfactant and cosurfactant on the particle size and EE was studied. A histological study revealed no adverse response of SLNs on sheep nasal mucosa. Transmission electron microscopic analysis showed spherical shape particles. Differential scanning calorimetry and X-ray diffraction studies indicated that the drug was completely encapsulated in a lipid matrix. In vitro drug release studies carried out in phosphate buffer (pH 6.6) indicated that the drug transport was of Fickian type. Gamma scintigraphic imaging in rabbits after i.n. administration showed rapid localization of the drug in the brain. Hence, OND SLNs is a promising nasal delivery system for rapid and direct nose-to-brain delivery. PMID:22802103

  18. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease.

    Science.gov (United States)

    Danielyan, Lusine; Schäfer, Richard; von Ameln-Mayerhofer, Andreas; Bernhard, Felix; Verleysdonk, Stephan; Buadze, Marine; Lourhmati, Ali; Klopfer, Tim; Schaumann, Felix; Schmid, Barbara; Koehle, Christoph; Proksch, Barbara; Weissert, Robert; Reichardt, Holger M; van den Brandt, Jens; Buniatian, Gayane H; Schwab, Matthias; Gleiter, Christoph H; Frey, William H

    2011-02-01

    Safe and effective cell delivery remains one of the main challenges in cell-based therapy of neurodegenerative disorders. Graft survival, sufficient enrichment of therapeutic cells in the brain, and avoidance of their distribution throughout the peripheral organs are greatly influenced by the method of delivery. Here we demonstrate for the first time noninvasive intranasal (IN) delivery of mesenchymal stem cells (MSCs) to the brains of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. IN application (INA) of MSCs resulted in the appearance of cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10⁶ MSCs applied intranasally, 24% survived for at least 4.5 months in the brains of 6-OHDA rats as assessed by quantification of enhanced green fluorescent protein (EGFP) DNA. Quantification of proliferating cell nuclear antigen-positive EGFP-MSCs showed that 3% of applied MSCs were proliferative 4.5 months after application. INA of MSCs increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase in terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine, 5'-triphosphate (dUTP)-biotin nick end labeling (TUNEL) staining of these areas. INA of EGFP-labeled MSCs prevented any decrease in the dopamine level in the lesioned hemisphere, whereas the lesioned side of the control animals revealed significantly lower levels of dopamine 4.5 months after 6-OHDA treatment. Behavioral analyses revealed significant and substantial improvement of motor function of the Parkinsonian forepaw to up to 68% of the normal value 40-110 days after INA of 1 × 10⁶ cells. MSC-INA decreased the concentrations of inflammatory cytokines-interleukin-1β (IL-1β), IL-2, -6, -12, tumor necrosis factor (TNF), interferon-γ (IFN-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF)-in the lesioned side to their

  19. Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

    Directory of Open Access Journals (Sweden)

    David Longbottom

    Full Text Available BACKGROUND: Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus. METHODOLOGY/PRINCIPAL FINDINGS: Three groups of sheep (groups 1, 2 and 3 were experimentally infected with different doses of C. abortus (5×10(3, 5×10(5 and 5×10(7 inclusion forming units (IFU, respectively prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b or were inoculated subcutaneously on day 70 of gestation with 2×10(6 IFU C. abortus (group 5. Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium. CONCLUSIONS/SIGNIFICANCE: The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and

  20. Formulation and Characterization of Nanoemulsion Intranasal Adjuvants: Effects of Surfactant Composition on Mucoadhesion and Immunogenicity

    OpenAIRE

    Wong, Pamela T.; Wang, Su He; Ciotti, Susan; Makidon, Paul E.; Smith, Douglas M.; Fan, Yongyi; Schuler, Charles F.; Baker, James R.

    2013-01-01

    Development of effective intranasal vaccines is of great interest due to their potential to induce both mucosal and systemic immunity. Here we produced oil-in-water nanoemulsion (NE) formulations containing various cationic and nonionic surfactants for use as adjuvants for the intranasal delivery of vaccine antigens. NE induced immunogenicity and antigen delivery are believed to be facilitated through initial contact interactions between the NE droplet and mucosal surfaces which promote prolo...

  1. The Reinforcing and Subjective Effects of Intravenous and Intranasal Buprenorphine in Heroin Users

    OpenAIRE

    Jones, Jermaine D.; Madera, Gabriela; Comer, Sandra D.

    2014-01-01

    Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphi...

  2. Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route.

    Science.gov (United States)

    Mittal, Deepti; Md, Shadab; Hasan, Quamrul; Fazil, Mohammad; Ali, Asgar; Baboota, Sanjula; Ali, Javed

    2016-01-01

    The aim of the present study was to prepare and evaluate a rasagiline-loaded chitosan glutamate nanoparticles (RAS-CG-NPs) by ionic gelation of CG with tripolyphosphate anions (TPP). RAS-loaded CG-NPs were characterized for particle size, size distribution, encapsulation efficiency and in vitro drug release. The mean particles size, polydispersity index (PDI) and encapsulation efficiency was found to be 151.1 ± 10.31, 0.380 ± 0.01 and 96.43 ± 4.23, respectively. Biodistribution of RAS formulations in the brain and blood of mice following intranasal (i.n.) and intravenous (i.v.) administration was performed using HPLC analytical method. The drug concentrations in brain following the i.n. of CG-NPs were found to be significantly higher at all the time points compared to both drug (i.n.) and drug CG-NPs (i.v.). The Cmax (999.25 ng/ml) and AUC (2086.60 ng h/ml) of formulation CG-NPs (i.n) were found to be significantly higher than CG-NPs (i.v.) and RAS solution (i.n.). The direct transport percentage (DTP%) values of RAS-loaded CG-NPs (i.n.) as compared to drug solution (i.n.) increased from 66.27 ± 1.8 to 69.27 ± 2.1%. The results showed significant enhancement of bioavailability in brain, after administration of the RAS-loaded CG-NPs which could be a substantial achievement of direct nose to brain targeting in Parkinson's disease therapy.

  3. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2015-01-01

    An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (-2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non-invasive sampling of saliva and/or urine.

  4. Intranasal dopamine reduces in vivo [123I]FP-CIT binding to striatal dopamine transporter: correlation with behavioral changes and evidence for Pavlovian conditioned dopamine response

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    Maria A de Souza Silva

    2016-04-01

    Full Text Available Purpose: Dopamine (DA, which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA, nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor.Methods: Rats were administered intranasal application of 3 mg/kg IN-DA and vehicle (VEH, with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT two hours following administration of the radioligand. Results: 1 After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered dopamine had central action and increased DA levels comparable to that found previously with L-DOPA administration. 2 DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant

  5. Repeated intranasal oxytocin administration in early life dysregulates the HPA axis and alters social behavior

    Science.gov (United States)

    Aggression and social stress are major welfare concerns when regrouping captive animals, with detrimental effects on health. In contrast, positive social interactions can reduce the adverse effects of social stress in humans and other animal species. This reduction may be mediated by oxytocin (OT), ...

  6. Development Effects of Oxytocin in Piglets by Intranasal or Subcutaneous Administration

    Science.gov (United States)

    Oxytocin (OT) is implicated in the regulation of social behaviors and reactivity to various stressors. Previous studies have evidenced that the effects of early experience, including postnatal social interactions, on socio-behavioral development are partly mediated by plasticity in peptide systems o...

  7. Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine

    Science.gov (United States)

    In the U.S., despite available swine influenza virus (SIV) vaccines, multiple influenza subtypes as well as antigenic and genetic variants within subtypes continue to circulate in the swine population. One of the challenges to control and eliminate SIV is that the currently used inactivated influenz...

  8. Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism.

    Science.gov (United States)

    Cates, Elizabeth C; Fattouh, Ramzi; Wattie, Jennifer; Inman, Mark D; Goncharova, Susanna; Coyle, Anthony J; Gutierrez-Ramos, José-Carlos; Jordana, Manel

    2004-11-15

    It is now well established that passive exposure to inhaled OVA leads to a state of immunological tolerance. Therefore, to elicit allergic sensitization, researchers have been compelled to devise alternative strategies, such as the systemic delivery of OVA in the context of powerful adjuvants, which are alien to the way humans are exposed and sensitized to allergens. The objectives of these studies were to investigate immune-inflammatory responses to intranasal delivery of a purified house dust mite (HDM) extract and to evaluate the role of GM-CSF in this process. HDM was delivered to BALB/c mice daily for 10 days. After the last exposure, mice were killed, bronchoalveolar lavage was performed, and samples were obtained. Expression/production of Th2-associated molecules in the lymph nodes, lung, and spleen were evaluated by real-time quantitative PCR and ELISA, respectively. Using this exposure protocol, exposure to HDM alone generated Th2 sensitization based on the expression/production of Th2 effector molecules and airway eosinophilic inflammation. Flow cytometric analysis demonstrated expansion and activation of APCs in the lung and an influx of activated Th2 effector cells. Moreover, this inflammation was accompanied by airways hyper-responsiveness and a robust memory-driven immune response. Finally, administration of anti-GM-CSF-neutralizing Abs markedly reduced immune-inflammatory responses in both lung and spleen. Thus, intranasal delivery of HDM results in Th2 sensitization and airway eosinophilic inflammation that appear to be mediated, at least in part, by endogenous GM-CSF production. PMID:15528378

  9. Evaluating the immunogenicity of an intranasal vaccine against nicotine in mice using the Adjuvant Finlay Proteoliposome (AFPL1).

    Science.gov (United States)

    Fraleigh, Nya L; Boudreau, Justin; Bhardwaj, Nitin; Eng, Nelson F; Murad, Yanal; Lafrenie, Robert; Acevedo, Reinaldo; Oliva, Reynaldo; Diaz-Mitoma, Francisco; Le, Hoang-Thanh

    2016-08-01

    Tobacco smoking is recognized as a global pandemic resulting in 6 million deaths per year. Despite a variety of anti-smoking products available to aid with tobacco cessation, the majority of people who attempt to quit smoking relapse within 6 months due to the addictive nature of nicotine. An immunotherapy approach could offer a promising treatment option by inducing a potent selective antibody response against nicotine in order to block its distribution to the brain and its addictive effects in the central nervous system. Our nicotine vaccine candidate was administered intranasally using the Neisseria meningitidis serogroup B Adjuvant Finlay Proteoliposome 1 (AFPL1) as a part of the delivery system. This system was designed to generate a robust immune response by stimulating IL-1β production through Toll-like receptor 4 (TLR4), a potent mechanism for mucosal immunity. The vaccine induced high antibody titers in mice sera in addition to inducing mucosal antibodies. The efficacy of our vaccine was demonstrated using in vivo challenge experiments with radioactive [(3)H]-nicotine, followed by an analysis of nicotine distribution in the lung, liver, blood and brain. Our results were encouraging as the nicotine concentration in the brain tissue of mice vaccinated with our candidate vaccine was four times lower than in non-vaccinated controls; suggesting that the anti-nicotine antibodies were able to block nicotine from crossing the blood brain barrier. In summary, we have developed a novel nicotine vaccine for the treatment of tobacco addiction by intranasal administration and also demonstrated that the AFPL1 can be used as a potential adjuvant for this vaccine design.

  10. Evaluating the immunogenicity of an intranasal vaccine against nicotine in mice using the Adjuvant Finlay Proteoliposome (AFPL1).

    Science.gov (United States)

    Fraleigh, Nya L; Boudreau, Justin; Bhardwaj, Nitin; Eng, Nelson F; Murad, Yanal; Lafrenie, Robert; Acevedo, Reinaldo; Oliva, Reynaldo; Diaz-Mitoma, Francisco; Le, Hoang-Thanh

    2016-08-01

    Tobacco smoking is recognized as a global pandemic resulting in 6 million deaths per year. Despite a variety of anti-smoking products available to aid with tobacco cessation, the majority of people who attempt to quit smoking relapse within 6 months due to the addictive nature of nicotine. An immunotherapy approach could offer a promising treatment option by inducing a potent selective antibody response against nicotine in order to block its distribution to the brain and its addictive effects in the central nervous system. Our nicotine vaccine candidate was administered intranasally using the Neisseria meningitidis serogroup B Adjuvant Finlay Proteoliposome 1 (AFPL1) as a part of the delivery system. This system was designed to generate a robust immune response by stimulating IL-1β production through Toll-like receptor 4 (TLR4), a potent mechanism for mucosal immunity. The vaccine induced high antibody titers in mice sera in addition to inducing mucosal antibodies. The efficacy of our vaccine was demonstrated using in vivo challenge experiments with radioactive [(3)H]-nicotine, followed by an analysis of nicotine distribution in the lung, liver, blood and brain. Our results were encouraging as the nicotine concentration in the brain tissue of mice vaccinated with our candidate vaccine was four times lower than in non-vaccinated controls; suggesting that the anti-nicotine antibodies were able to block nicotine from crossing the blood brain barrier. In summary, we have developed a novel nicotine vaccine for the treatment of tobacco addiction by intranasal administration and also demonstrated that the AFPL1 can be used as a potential adjuvant for this vaccine design. PMID:27622215

  11. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

    Science.gov (United States)

    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. PMID:26278659

  12. Comparison of desmopressin (DDAVP tablet and intranasal spray in the treatment of central diabetes insipidus

    Directory of Open Access Journals (Sweden)

    "Bagher Larijani

    2005-07-01

    Full Text Available Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing, biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43% in tablet group and dyspnea (7% in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant, respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006. Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.

  13. Position on zinc delivery to olfactory nerves in intranasal insulin phase I-III clinical trials.

    Science.gov (United States)

    Hamidovic, A

    2015-11-01

    Zinc in pancreatic insulin is essential for processing and action of the peptide, while in commercial preparations zinc promotes hexameric structure and prevents aggregate formation. In 2002, for the first time, insulin was delivered to humans intranasally with resulting cerebrospinal fluid insulin increases, but steady peripheral insulin levels. The novel method of increasing brain insulin levels without changes in the periphery resulted in an expansion of brain insulin research in clinical trials. As pre-clinical research has shown that brain insulin modulates a number functions, including food cravings and eating behavior, learning and memory functions, stress and mood regulation; realization of beneficial effects of insulin in modulating these functions in clinical populations became a possibility with the new direct-to-brain insulin delivery methodology. However, zinc, being integral to insulin structure and function, is neurotoxic, and has resulted in adverse effects to human health. In the last century, intranasal zinc was given preventively during the time of polio outbreak, and in the 21st century intranasal zinc was widely used over the counter to prevent common cold. In both cases, patients experienced partial or complete loss of smell. This paper is the first one to analyze zinc salts and concentrations of those two epidemiological adversities and directly compare formulations distributed to the public with animal toxicity data. The information gained from animal and epidemiological data provides a foundation for the formation of opinion given in this paper regarding safety of intranasal zinc in emerging clinical trials with intranasal insulin.

  14. Intranasal T-LysYal® as adjunctive therapy for patients after functional endoscopic sinus surgery.

    Science.gov (United States)

    Gelardi, M; Taliente, S; Fiorella, M L; Quaranta, N; De Candia, N; Russo, C; Mola, P; Ciofalo, A; Zambetti, G; Cantone, E; Arnone, F; Macchi, A; Rosso, P; Ciprandi, G

    2016-01-01

    Functional Endoscopic Sinus Surgery (FESS) is a common day surgery technique for upper airway disorders. Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert reparative, anti-inflammatory and immune-modulating activities. Recently, a new intranasal HA formulation has been proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (RinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 83 patients (49 males and 34 females mean age 45.4±6.2 years) treated with FESS. All patients were treated with isotonic saline solution for 4 weeks, and a sub-group (active group) was also treated with intranasal T-LysYal®. Patients were visited at baseline, after treatment, and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells in comparison to isotonic solution. In conclusion, the present study demonstrates that intranasal T-LysYal® is able to significantly improve patients after FESS and its effect is long lasting. PMID:27049103

  15. Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

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    Lisa A Parr

    2014-09-01

    Full Text Available There are currently no drugs approved for the treatment of social deficits associated with autism spectrum disorders (ASD. One hypothesis for these deficits is that individuals with ASD lack the motivation to attend to social cues because those cues are not implicitly rewarding. Therefore, any drug that could enhance the rewarding quality of social stimuli could have a profound impact on the treatment of ASD, and other social disorders. Oxytocin (OT is a neuropeptide that has been effective in enhancing social cognition and social reward in humans. The present study examined the ability of OT to selectively enhance learning after social compared to nonsocial reward in rhesus monkeys, an important species for modeling the neurobiology of social behavior in humans. Monkeys were required to learn an implicit visual matching task after receiving either intranasal (IN OT or Placebo (saline. Correct trials were rewarded with the presentation of positive and negative social (play faces/threat faces or nonsocial (banana/cage locks stimuli, plus food. Incorrect trials were not rewarded. Results demonstrated a strong effect of socially-reinforced learning, monkeys’ performed significantly better when reinforced with social versus nonsocial stimuli. Additionally, socially-reinforced learning was significantly better and occurred faster after IN-OT compared to placebo treatment. Performance in the IN-OT, but not Placebo, condition was also significantly better when the reinforcement stimuli were emotionally positive compared to negative facial expressions. These data support the hypothesis that OT may function to enhance prosocial behavior in primates by increasing the rewarding quality of emotionally positive, social compared to emotionally negative or nonsocial images. These data also support the use of the rhesus monkey as a model for exploring the neurobiological basis of social behavior and its impairment.

  16. Intranasal delivery of plasma and platelet growth factors using PRGF-Endoret system enhances neurogenesis in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Eduardo Anitua

    Full Text Available Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimer's disease (AD induced by a combination of toxic amyloid-β peptide (Aβ and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret, an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1 mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU, doublecortin (DCX, and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD.

  17. Preventive Activity against Influenza (H1N1 Virus by Intranasally Delivered RNA-Hydrolyzing Antibody in Respiratory Epithelial Cells of Mice

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    Seungchan Cho

    2015-09-01

    Full Text Available The antiviral effect of a catalytic RNA-hydrolyzing antibody, 3D8 scFv, for intranasal administration against avian influenza virus (H1N1 was described. The recombinant 3D8 scFv protein prevented BALB/c mice against H1N1 influenza virus infection by degradation of the viral RNA genome through its intrinsic RNA-hydrolyzing activity. Intranasal administration of 3D8 scFv (50 μg/day for five days prior to infection demonstrated an antiviral activity (70% survival against H1N1 infection. The antiviral ability of 3D8 scFv to penetrate into epithelial cells from bronchial cavity via the respiratory mucosal layer was confirmed by immunohistochemistry, qRT-PCR, and histopathological examination. The antiviral activity of 3D8 scFv against H1N1 virus infection was not due to host immune cytokines or chemokines, but rather to direct antiviral RNA-hydrolyzing activity of 3D8 scFv against the viral RNA genome. Taken together, our results suggest that the RNase activity of 3D8 scFv, coupled with its ability to penetrate epithelial cells through the respiratory mucosal layer, directly prevents H1N1 virus infection in a mouse model system.

  18. A positive effect of intranasal insulin on spatial memory in rats with neonatal diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Oxana V. Chistyakova

    2011-12-01

    Full Text Available Type 2 diabetes mellitus (T2DM is associated with cognitive impairments. However, their causal factors and the approaches to be used in their treatment have not been fully clarified and further study is needed. The aim of this work was to study the effect of intranasal insulin (I-I on cognitive functions in rats with experimental T2DM. Neonatal rats (5 days old were treated with an intraperitoneal (i.p. administration of a single dose of streptozotocin (STZ (80 mg/kg i.p. which in adult animals leads to impairment of glucose tolerance and mild hyperglycemia, typical of T2DM. The insulin receptor binding in the synaptosomal and liver membranes was evaluated with [125I]-insulin, and the IRS2 expression in the brain was estimated by RT-PCR. Daily I-I (0.48 IU/day or placebo were delivered to diabetic and non-diabetic rats during a week before and the 39 days of cognition experiments. Spatial memory and learning were studied in a Morris water-maze (MWM test. The MWM test showed that, in the case of diabetic rats, the latent period for finding the platform (escape latency and the swimming path length were increased, and the number of annulus crossings decreased compared with control (P<0.05. I-I normalized cognitive functions in diabetic rats but had no effect on those of non-diabetic animals. Specific insulin binding in the liver of diabetic rats was decreased, indicating peripheral insulin resistance, but changed very little in the brain. In the hypothalamus of diabetic rats, but not in the cortex and the olfactory bulbs, the expression of IRS2 was reduced by 68% compared with control and was restored after I-I delivery. Rats with neonatal T2DM had cognitive deficit likely associated with impaired IRS2-mediated signaling pathways in the diabetic brain and eliminated by I-I treatment.

  19. Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Spray (Nasulin™) Administered to Healthy Male Volunteers:

    Science.gov (United States)

    Leary, Andrew C.; Dowling, Muiris; Cussen, Kathleen; O'Brien, Jackie; Stote, Robert M.

    2008-01-01

    Background The pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals proprietary intranasal (IN) insulin formulation (Nasulin™) were studied in healthy volunteers. Methods Thirteen fasting healthy male volunteers received five doses of medication (one dose of 4 international units [IU] subcutaneous (SC) regular insulin and four doses of 25 IU IN insulin) at least 48 h apart. Serum insulin, serum C-peptide, and plasma glucose were measured in the 4 h after dosing. Profiles were compared for IN insulin spray following administration into the dominant nostril (more open at time of dosing) and into the nondominant nostril (less open at time of dosing). Results The formulation was generally well tolerated. A rise in serum insulin levels accompanied by a decrease in plasma glucose was seen following all doses. For IN doses, peak insulin levels were generally attained in 10–20 min and remained elevated for approximately 40–50 min; the resultant effect on glucose peaked at 40 min and waned approximately 2 h postdosing. As reported in other studies, the interindividual response to insulin was variable. The comparative absorption of IN insulin relative to SC insulin was 12.0% (dominant nostril) or 15.4% (nondominant nostril) over 2 h. This increased somewhat if sneezers and volunteers with moderately blocked nostrils were removed from the analysis. Conclusions This IN formulation was generally well tolerated and relatively well absorbed. While both insulin data (maximal plasma concentration and area under the plasma concentration time curve) and glucose data (% fall) support a trend toward better absorption from the nondominant nostril, this did not reach statistical significance. Nasulin can be administered without reference to the nasal cycle. PMID:19885293

  20. Effects of intranasal phototherapy on nasal microbial flora in patients with allergic rhinitis.

    Directory of Open Access Journals (Sweden)

    Yavuz Selim Yıldırım

    2013-09-01

    Full Text Available The objective of this study was to investigate the effect of intranasal phototherapy on nasal microbial flora in patients with allergic rhinitis.This prospective, self-comparised, single blind study was performed on patients with a history of at least two years of moderate-to-severe perennial allergic rhinitis that was not controlled  by  anti-allergic drugs.  Thirty-one  perennial  allergic rhinitis  patients  were enrolled in this study. Before starting the test population on their intranasal phototherapy, the same trained person took a nasal culture from each subject by applying a sterile cotton swab  along  each  side  of  the  nostril  and  middle  meatus.  Each  intranasal  cavity was irradiated three times a week for two weeks with increasing doses of irradiated. At the end  of  the  intranasal phototherapy,  nasal cultures were again obtained  from  the  each nostril The study found that after intranasal phototherapy, the scores for total nasal symptoms decreased significantly but bacterial proliferation was not significantly different before and after phototherapy.We  have  shown  that  intranasal  phototherapy  does  not  change  the  aerobic  nasal microbial flora in patients with perennial allergic rhinitis.

  1. AN in vitro evaluation of a carmustine-loaded Nano-co-Plex for potential magnetic-targeted intranasal delivery to the brain.

    Science.gov (United States)

    Akilo, Olufemi D; Choonara, Yahya E; Strydom, André M; du Toit, Lisa C; Kumar, Pradeep; Modi, Girish; Pillay, Viness

    2016-03-16

    Targeted delivery of carmustine (BCNU), an efficient brain tumor therapeutic, has been challenged with bioavailability issues due to the Blood Brain Barrier (BBB). The currently effective delivery approach is by implants at the site of the tumor, but this is highly invasive. The intranasal route, which is non-invasive and bypasses the BBB, may be alternative route for delivering BCNU to the brain. In this work, polyvinyl alcohol/polyethyleneimine/fIuorecein isothiocyanate complex (Polyplex) coated iron-oxide nanoparticles (Magnetite) were synthesized employing co-precipitation, epoxidation and EDC/NHS coupling reactions. The Polyplex coated magnetite (Nano-co-Plex) was loaded with BCNU for potential magnetically targeted delivery to the brain following intranasal administration. The Nano-co-Plex was characterized employing Thermogravimetric analysis (TGA), Superconducting Quantum Interference Device (SQUID) magnetometry, Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X-ray Diffractometry (XRD), Transmission Electron Microscopy (TEM) and Zetasize analysis. Results revealed superparamagnetic hexagonally shaped "core-shell" nanoparticles with cell labeling attributes, of size ranging between 30-50 nm, and a zeta potential value of + 32 ± 2 mV. The Nano-co-Plex synthesized was found to possess high degree of crystallinity with 32% Polyplex coating. The loading and release studies indicated a time-dependent loading with maximum loading capacity of 176.82 μg BCNU/mg of the carrier and maximum release of 75.8% of the loaded BCNU. Cytotoxicity of the BCNU-loaded Nano-co-Plex displayed superiority over the conventional BCNU towards human glioblastoma (HG) cells. Cell studies revealed enhanced uptake and internalization of BCNU-loaded Nano-co-plex in HG cells in the presence of an external magnetic field. These Nano-co-Plexes may be ideal as an intranasal magnetic drug targeting device for BCNU delivery. PMID:26806465

  2. Poly(ethylene oxide/propylene oxide) copolymer thermo-reversible gelling system for the enhancement of intranasal zidovudine delivery to the brain.

    Science.gov (United States)

    Ved, Parag M; Kim, Kwonho

    2011-06-15

    The purpose of this study was to investigate the olfactory transfer of zidovudine (ZDV) after intranasal (IN) administration and to assess the effect of thermoreversible gelling system on its absorption and brain uptake. The nasal formulation was prepared by dissolving ZDV in pH 5.5 phosphate buffer solution comprising of 20% polyethylene oxide/propylene oxide (Poloxamer 407, PLX) as thermoreversible gelling agent and 0.1% n-tridecyl-β-D-maltoside (TDM) as permeation enhancer. This formulation exhibited a sufficient stability and an optimum gelation profile at 27-30 °C. The in vitro permeation studies across the freshly excised rabbit nasal mucosa showed a 53% increase in the permeability of ZDV from the formulation. For in vivo evaluation, the drug concentrations in the plasma, cerebrospinal fluid (CSF) and six different regions of the brain tissues, i.e. olfactory bulb (OB), olfactory tract (OT), anterior, middle and posterior segments of cerebrum (CB), and cerebellum (CL) were determined by LC/MS method following IV and IN administration in rabbits at a dose of 1mg/kg. The IN administration of Poloxamer 407 and TDM based formulation showed a systemic bioavailability of 29.4% while exhibiting a 4 times slower absorption process (t(max) = 20 min) than control solution (t(max) = 5 min). The CSF and brain ZDV levels achieved after IN administration of the gelling formulation were approximately 4.7-56 times greater than those attained after IV injection. The pharmacokinetic and brain distribution studies revealed that a polar antiviral compound, ZDV could preferentially transfer into the CSF and brain tissue via an alternative pathway, possibly olfactory route after intranasal administration.

  3. The Efficacy of Intranasal Desmopressin as an Adjuvant in the Acute Renal Colic Pain Management

    OpenAIRE

    Kambiz Masoumi; Ali Asgari Darian; Arash Forouzan; Hassan Barzegari; Fakher Rahim; Maryam Feli; Mehdi Fallah Bagher Sheidaii; Samaneh Porozan

    2014-01-01

    The aim of this study was to compare analgesic effect of intramuscular (IM) sodium diclofenac and intranasal desmopressin combination with IM sodium diclofenac alone in patients with acute renal colic. In this randomized double-blind clinical trial, all patients aged 18 to 55 years who were diagnosed as acute renal colic and met the inclusion and exclusion criteria were randomized into two groups to receive 40 μg intranasal desmopressin spray and 75 mg IM sodium diclofenac combination (Group ...

  4. Safety of Intranasal Fentanyl in the Out-of-Hospital Setting

    DEFF Research Database (Denmark)

    Karlsen, Anders P H; Pedersen, Danny M B; Trautner, Sven;

    2014-01-01

    : In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses...

  5. Early experience of radio frequency coblation in the management of intranasal and sinus tumors.

    Science.gov (United States)

    Syed, Mohammed Iqbal; Mennie, Joanna; Williams, Alun T

    2012-02-01

    The purpose of this study was to evaluate the safety and efficacy of the use of radiofrequency coblation for endoscopic resection of intranasal and sinus tumors. A review was conducted of 15 adult patients with intranasal and or sinus tumors endoscopically treated with radio frequency coblation between November 2008 and November 2010 at St. John's Hospital at Livingston, a tertiary referral center that covers otolaryngology services for the southeast of Scotland. Fifteen patients with intranasal and sinus tumors were treated with transnasal endoscopic resection using radiofrequency coblation. The tumors included inverted papilloma (seven), paraganglioma (one), glomangiopericytoma (one), capillary hemangioma (one), hemangiopericytoma (one), juvenile angiofibroma (one), juvenile ossifying fibroma (one), oncocytic adenoma (one), and transitional cell carcinoma (one). We found that radiofrequency coblation is a useful and safe tool associated with minimal blood loss (<200 mL to 600 mL) in the resection of these tumors, and the average operating time was 1.67 hours. Radio frequency is a rapidly evolving technique and in the future will have an increasing role to play in the endoscopic resection of intranasal and sinus tumors.

  6. Cortisol, but not intranasal insulin, affects the central processing of visual food cues

    NARCIS (Netherlands)

    D.S. Ferreira de Sá; A. Schulz; F.E. Streit; J.D. Turner; M.S. Oitzl; T.D. Blumenthal; H. Schächinger

    2014-01-01

    Stress glucocorticoids and insulin are important endocrine regulators of energy homeostasis, but little is known about their central interaction on the reward-related processing of food cues. According to a balanced group design, healthy food deprived men received either 40IU intranasal insulin (n=1

  7. Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers.

    OpenAIRE

    Higgins, P. G.; Phillpotts, R J; Scott, G. M.; Wallace, J; Bernhardt, L L; Tyrrell, D. A.

    1983-01-01

    In a double-blind, placebo-controlled study, self-administered intranasal human interferon alpha A produced by recombinant DNA technology was given both before and after virus challenge with a respiratory coronavirus. The incidence of colds, the severity of symptoms and signs, and virus replication were all reduced in subjects receiving interferon as compared with those given placebo.

  8. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, Elin T. G.; van Leeuwen, Janneke C.; Brand, Paul L. P.; Duiverman, Eric J.; de Jongh, Frans H. C.; Thio, Bernard J.; Driessen, Jean M. M.

    2012-01-01

    Rationale Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a double-blind,

  9. Comparative Study of Intranasal Midazolam and Intravenous Benzodiazepines in Control of Seizures in Children

    Directory of Open Access Journals (Sweden)

    Janki Panchal

    2013-02-01

    Full Text Available Background: Seizures are very common in pediatric patients. As duration of seizures impacts morbidity and mortality to child’s life, control of seizures should be achieved as early as possible, preferably at home. Rectal diazepam and intranasal midazolam are available methods for control of seizures and can be learnt by parents. Methods: We assessed safety and efficacy of intranasal midazolam for control of seizures and also compared its effect with other benzodiazepines given by intravenous route. Results: Among 84 patients, success rate of treatment with Midazolam (intranasal was 45.5% and success rate with Benzodiazepines (intravenous was 90%. The difference is statistically significant. In present study, average time recorded to give drug after arrival at hospital in IN Midazolam group was 0.379 min, where as it was 1.598 min in IV Benzodiazepine group. Average time for cessation of seizures after giving drug was 3.001 min in IN Midazolam group, where as it was 1.009 min in IV Benzodiazepine group. Conclusion: Intra-venous route for control of seizures is most effective compare to Inta-nasal Midazolam. However intranasal Midazolam can be use full when IV access is not available at home or during transport of patient to health care centre. [Natl J of Med Res 2013; 3(1.000: 30-33

  10. Intranasal LH-RH treatment of cryptorchidism. A clinical trial and 5 years follow-up

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Mauritzen, K; Skakkebaek, N E

    1987-01-01

    The effect of intranasal LH-RH on cryptorchidism was investigated in 45 prepubertal boys with 68 undescended testes. A daily dose of 1.2 mg LH-RH was given for 4 weeks. A total of 16 testes (24%) descended. Follow-up examination 5 years later showed that relapse had occurred in two cases. Fifty-t...

  11. Effect of an intranasal conrticosteroid on exercide induced bronchocostriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, E.T.; Leeuwen, J.C. van; Brand, P.L.; Duiverman, E.J.; Jongh, de F.H.C.; Thio, B.J.; Driessen, J.M.

    2012-01-01

    Rationale: Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a double-blin

  12. Preparation of lorazepam-loaded microemulsions for intranasal delivery and its pharmacokinetics.

    Science.gov (United States)

    Yao, J; Hou, L; Zhou, J P; Zhang, Z Q; Sun, L

    2009-10-01

    The purpose of this study was to develop a microemulsion system for intranasal delivery of lorazepam. The phase behavior and properties of microemulsions were characterized in a pseudo-ternary system composed of Cremophor EL 35/Transcutol P/Lauroglycol FCC or Labrafil M 1944CS/water, and intranasal absorption of lorazepam from microemulsions was investigated in rabbit. The microemulsions, comprising of FCC, Cremophor EL 35/Transcutol P (1.5:1) and water, were optimal for intranasal delivery of lorazepam. These systems had a higher solubilization capacity with the particle size of microemulsions at 0.38 mg/kg had the larger AUC(0-t), the longer half-life and the prolonged circulation time with the mean bioavailability of 80.84% for ME2 and 63.48% for ME8 as compared to the intramuscular injection at 0.16 mg/kg. These results indicate that microemulsions may bea promising approach for the intranasal delivery of lorazepam. PMID:19947165

  13. Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: preparation, optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging.

    Science.gov (United States)

    Salama, Alaa Hamed; Aburahma, Mona Hassan

    2016-09-01

    To circumvent the low and erratic absorption of orally administrated cinnarizine (CN), intranasal lyophilized gels containing unsaturated fatty acid liposomes (ufasomes) and encapsulating CN were prepared from oleic acid using a simple assembling strategy. The effects of varying drug concentration and cholesterol percentage on ufasomes size, polydispersity index and entrapment efficiency were investigated using 3(1)4(1) full factorial design. The optimized ufasomes that contained 14% cholesterol relative to oleic acid displayed spherical morphology with average size of 788 nm and entrapment efficiency of 80.49%. To overcome the colloidal instability of CN-loaded ufasomes dispersions and their short residence time in the nasal cavity, the ufasomes were incorporated into mucoadhesive hydrogels that were lyophilized into unit dosage forms for accurate dosing. Scanning electron micrographs of the lyophilized gel revealed that the included ufasomes were intact, non-aggregating and maintained their spherical morphology. Rheological characterization of reconstituted ufasomal lyophilized gel ensured ease of application. Furthermore, the gel induced minor histopathological alterations in sheeps' nasal mucosa. Ex-vivo confocal laser imaging confirmed the ability of ufasomes to penetrate deep through nasal mucosa layers. The results highlighted in the current work confirm the feasibility of using CN-loaded ufasomal gels for intranasal drug delivery.

  14. Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: preparation, optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging.

    Science.gov (United States)

    Salama, Alaa Hamed; Aburahma, Mona Hassan

    2016-09-01

    To circumvent the low and erratic absorption of orally administrated cinnarizine (CN), intranasal lyophilized gels containing unsaturated fatty acid liposomes (ufasomes) and encapsulating CN were prepared from oleic acid using a simple assembling strategy. The effects of varying drug concentration and cholesterol percentage on ufasomes size, polydispersity index and entrapment efficiency were investigated using 3(1)4(1) full factorial design. The optimized ufasomes that contained 14% cholesterol relative to oleic acid displayed spherical morphology with average size of 788 nm and entrapment efficiency of 80.49%. To overcome the colloidal instability of CN-loaded ufasomes dispersions and their short residence time in the nasal cavity, the ufasomes were incorporated into mucoadhesive hydrogels that were lyophilized into unit dosage forms for accurate dosing. Scanning electron micrographs of the lyophilized gel revealed that the included ufasomes were intact, non-aggregating and maintained their spherical morphology. Rheological characterization of reconstituted ufasomal lyophilized gel ensured ease of application. Furthermore, the gel induced minor histopathological alterations in sheeps' nasal mucosa. Ex-vivo confocal laser imaging confirmed the ability of ufasomes to penetrate deep through nasal mucosa layers. The results highlighted in the current work confirm the feasibility of using CN-loaded ufasomal gels for intranasal drug delivery. PMID:25996631

  15. Use of flagellin and cholera toxin as adjuvants in intranasal vaccination of mice to enhance protective immune responses against uropathogenic Escherichia coli antigens.

    Science.gov (United States)

    Asadi Karam, Mohammad Reza; Habibi, Mehri; Bouzari, Saeid

    2016-09-01

    Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) are among the most common infections in human. Antibiotics are common therapy for UTIs, but increase in antibiotic resistance will complicate future treatment of the infections, making the development of an efficacious UTI vaccine more urgent. In this study, we have evaluated intranasally the efficacy of FliC and FimH antigens of UPEC in different vaccine formulations with and without cholera toxin (CT) adjuvant. Immunization of mice with FliC in fusion form or admixed with FimH elicited higher levels of serum, mucosal and cell-mediated responses than FimH alone. Furthermore, the use of CT in synergism with FliC resulted in the stimulation of a mixed Th1 and Th2 responses against FimH and FliC as antigen and maintained the antibody responses for at least 24 weeks following the last vaccine dose. Of the vaccine preparations, Fusion, Fusion + CT, and FimH admixed with FliC and CT showed the best protection against UPEC. These data indicated that intranasal administration of a FliC and CT adjuvant-based vaccine has the potential to provide protective responses against UPEC strains.

  16. A dose-response evaluation of inactivated influenza vaccine given intranasally and intramuscularly to healthy young adults.

    Science.gov (United States)

    Atmar, Robert L; Keitel, Wendy A; Cate, Thomas R; Munoz, Flor M; Ruben, Fred; Couch, Robert B

    2007-07-20

    Epidemic influenza occurs annually throughout the world and is accompanied by excess morbidity and mortality. Increasing the antigen content and topical administration of vaccine are two strategies being explored to improve the immune responses to trivalent inactivated influenza vaccine (TIV). We conducted a randomized, double-blind, placebo-controlled trial to compare the immunogenicity and reactogenicity of intramuscular (IM), intranasal (IN), or combined IM and IN administration of a contemporary US vaccine formulation at escalating dosage levels in young healthy adults. Two hundred forty three healthy adults between the ages of 18 and 45 years received 15, 30, or 60mcg of trivalent inactivated influenza vaccine by either IN, IM or both routes, 120mcg of vaccine IM, or placebo IN and IM. All dosages and routes of vaccine administration were well-tolerated. A bad taste and mild nasal discomfort were more likely to be reported when influenza vaccine was administered IN, while arm tenderness was more common after IM administration. Significant increases in geometric mean serum antibody titers in both HAI and Nt assays were seen in all of the groups receiving influenza vaccine for all test antigens (Por=32 were higher following delivery of the study vaccines by an IM route than by the IN route, but significant increases in serum antibody were seen after IN vaccination. Nasal IgA antibody responses were more common when vaccine was administered IN; and, when the IN dosage was increased, the primary benefit from IN vaccine over IM vaccine appeared to be greater induction of nasal secretory antibody.

  17. Intranasal steroids: managing allergic rhinitis and tailoring treatment to patient preference.

    Science.gov (United States)

    Meltzer, Eli O

    2005-01-01

    Allergic rhinitis (AR) can have a significant impact on patient quality of life (QoL), affecting learning ability and work productivity. Both the consequences of the impairment and the costs of treatment are associated with a large economic burden. The management of AR includes allergen avoidance, pharmacotherapy, and immunotherapy. Current pharmacotherapy options are oral and intranasal antihistamines, intranasal corticosteroids (INS), intranasal chromones, oral and intranasal decongestants, oral and intranasal anticholinergic agents, and antileukotrienes. A number of guidelines recommend INS as first-line treatment for persistent and moderate-to-severe AR. Although both patient and physician concern over the long-term safety of oral systemic steroids has previously prevented widespread use of INS, it is important to note that they have a superior risk/benefit ratio compared with other monotherapies. Indeed, the limited systemic bioavailability of INS agents, when used at recommended doses, has resulted in very low rates of systemic adverse effects, as shown by a lack of either hypothalamic-pituitary-adrenal axis or growth suppression. Large, controlled clinical studies have shown comparable efficacy and safety among the newer INS; therefore, clinicians may need to consider other factors, such as good patient compliance, when selecting an appropriate INS agent for a patient. In addition, patients often prefer one agent over another, and compliance may be improved by selecting the preferred agent. The development of two new questionnaires, the Clinical Practice Patient Preference Questionnaire and the Clinical Trial Patient Preference Questionnaire, may prove useful in selecting the optimal treatment regimen for patients. PMID:16541967

  18. Intranasal Dopamine Reduces In Vivo [123I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response

    Science.gov (United States)

    de Souza Silva, Maria A.; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P.; Sadile, Adolfo G.; Beu, Markus; Müller, H.-W.; Nikolaus, Susanne

    2016-01-01

    Purpose: Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor. Methods: Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. Results: (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. Conclusions: The results: (a

  19. An Evaluation of Intranasal Sufentanil and Dexmedetomidine for Pediatric Dental Sedation

    Directory of Open Access Journals (Sweden)

    James M. Hitt

    2014-03-01

    Full Text Available Conscious or moderate sedation is routinely used to facilitate the dental care of the pre- or un-cooperative child. Dexmedetomidine (DEX has little respiratory depressant effect, possibly making it a safer option when used as an adjunct to either opioids or benzodiazepines. Unlike intranasal (IN midazolam, IN application of DEX and sufentanil (SUF does not appear to cause much discomfort. Further, although DEX lacks respiratory depressive effects, it is an α2-agonist that can cause hypotension and bradycardia when given in high doses or during prolonged periods of administration. The aim of this feasibility study was to prospectively assess IN DEX/SUF as a potential sedation regimen for pediatric dental procedures. After IRB approval and informed consent, children (aged 3–7 years; n = 20 from our dental clinic were recruited. All patients received 2 μg/kg (max 40 μg of IN DEX 45 min before the procedure, followed 30 min later by 1 μg/kg (max 20 μg of IN SUF. An independent observer rated the effects of sedation using the Ohio State University Behavior Rating Scale (OSUBRS and University of Michigan Sedation Scale (UMSS. The dentist and the parent also assessed the efficacy of sedation. Dental procedures were well tolerated and none were aborted. The mean OSUBRS procedure score was 2.1, the UMSS procedure score was 1.6, and all scores returned to baseline after the procedure. The average dentist rated quality of sedation was 7.6 across the 20 subjects. After discharge, parents reported one child with prolonged drowsiness and one child who vomited at home. The use of IN DEX supplemented with IN SUF provided both an effective and tolerable form of moderate sedation. Although onset and recovery are slower than with oral (PO midazolam and transmucosal fentanyl, the quality of the sedation may be better with less risk of respiratory depression. Results from this preliminary study showed no major complications from IN delivery of these agents.

  20. Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra Envenomation

    Directory of Open Access Journals (Sweden)

    Matthew R. Lewin

    2014-01-01

    Full Text Available Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice. Methods. Mice received intraperitoneal injections of Naja naja venom 2.5 to 10 times the estimated LD50 and then received 5 μL neostigmine (0.5 mg/mL or 5 μL normal saline by nasal administration. Animals were observed up to 12 hours and survivors were euthanized. Results. 100% of control mice died. Untreated mice injected with 2.5× LD50 Naja naja died at average 193 minutes after injection, while 10 of 15 (67% of treated mice survived and were behaviorally normal by 6 hours (P<0.02. In the 5× LD50 group, survival was prolonged from 45 minutes to 196 minutes (P=0.01 and for 10× LD50 mice, survival increased from 30 to 175 minutes (P<0.02. Conclusion. This pilot suggests that intranasal drugs can improve survival and is the first direct demonstration that such an approach is plausible, suggesting means by which treatment could be initiated before reaching the hospital. Further investigation of this approach to neurotoxic and other types of envenomation is warranted.

  1. Transient facial nerve paralysis (Bell's palsy following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin.

    Directory of Open Access Journals (Sweden)

    David J M Lewis

    Full Text Available BACKGROUND: An association was previously established between facial nerve paralysis (Bell's palsy and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT adjuvant. The individual component(s responsible for paralysis were not identified, and the vaccine was withdrawn. METHODOLOGY/PRINCIPAL FINDINGS: Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63, underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63. CONCLUSIONS/SIGNIFICANCE: While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes.

  2. Immune adjuvant effect of V. cholerae O1 derived Proteoliposome coadministered by intranasal route with Vi polysaccharide from Salmonella Typhi.

    Science.gov (United States)

    Acevedo, Reinaldo; Callicó, Adriana; Aranguren, Yisabel; Zayas, Caridad; Valdés, Yolanda; Pérez, Oliver; García, Luis; Ferro, Valerie A; Pérez, José Luis

    2013-01-01

    The proteoliposome derived from Vibrio cholerae O1 (PLc) is a nanoscaled structure obtained by a detergent extraction process. Intranasal (i.n) administration of PLc was immunogenic at mucosal and systemic level vs. V. cholerae; however the adjuvant potential of this structure for non-cholera antigens has not been proven yet. The aim of this work was to evaluate the effect of coadministering PLc with the Vi polysaccharide antigen (Poli Vi) of S. Typhi by the i.n route. The results showed that Poli Vi coadministered with PLc (PLc+Poli Vi) induce a higher IgA response in saliva (p0.05) to that induced in a group of mice immunised by the parenteral route with the Cuban anti-typhoid vaccine vax-TyVi, although this vaccine did not induce a mucosal response. In conclusion, this work demonstrates that PLc can be used as a mucosal adjuvant to potentiate the immune response against a polysaccharide antigen like Poli Vi.

  3. Morning or evening administration of nasal calcitonin?

    DEFF Research Database (Denmark)

    Schlemmer, A; Ravn, Pernille; Hassager, C;

    1997-01-01

    The purpose of this study was to examine the effect of intranasal salmon calcitonin (sCT) administration (200 IE), given either in the morning (8:00) or evening (21:00), on the known circadian variation in biochemical markers of bone turnover. An open, placebo-controlled, randomized, crossover......). Serum osteocalcin (sOC) was measured by radioimmunoassay (RIA). The first 24 h study was performed without intervention. Prior to this control study the participants were randomized to either morning (8:00) or evening (21:00) sCT (200 IE). sCT administrations were given 4-5 days prior to and during the...... in late afternoon. Both morning and evening administration of sCT significantly decreased the urinary excretion of CrossLaps/Cr approximately 3-6 h after administration with a subsequent rebound effect. sOC did not exhibit a significant circadian variation and was not affected by the calcitonin. The...

  4. Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis

    Directory of Open Access Journals (Sweden)

    Yasuyuki Noyama

    2016-07-01

    Conclusions: These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation.

  5. ANESTHETICS EFFECTS OF INTRANASAL OR INTRAMUSCULAR ASSOCIATION OF MIDAZOLAM AND RACEMIC OR S+ KETAMINE IN BUDGERIGARS (Melopsittacus undulatus)

    OpenAIRE

    Gustavo Aléssio Trevisan; Everton Leonardi da Silva; Anderson Luiz de Carvalho; Rafael Messias Luiz

    2016-01-01

    Intranasal anesthesia in birds is considered a safe, simple and efficient technique. The aim of this study was compare the anesthetic effects of midazolam (5 mg.kg-1) with racemic (R) or S+ (S) ketamine (15 mg.kg-1), administered intranasally (IN) or intramuscularly (IM) in budgerigars (Melopsittacus undulatus). Eight budgerigars were used in a crossover design with four treatments: INR, INS, IMR and IMS. Onset time, dorsal recumbency time duration, total anesthesia time, total recovery time,...

  6. Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis: effect of instillation volume and form of anesthesia.

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    Mark A Miller

    Full Text Available Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane vs. parenteral (ketamine/xylazine anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique.

  7. The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT).

    Science.gov (United States)

    Cardoso, Christopher; Ellenbogen, Mark A; Linnen, Anne-Marie

    2014-02-01

    Evidence suggests that intranasal oxytocin enhances the perception of emotion in facial expressions during standard emotion identification tasks. However, it is not clear whether this effect is desirable in people who do not show deficits in emotion perception. That is, a heightened perception of emotion in faces could lead to "oversensitivity" to the emotions of others in nonclinical participants. The goal of this study was to assess the effects of intranasal oxytocin on emotion perception using ecologically valid social and nonsocial visual tasks. Eighty-two participants (42 women) self-administered a 24 IU dose of intranasal oxytocin or a placebo in a double-blind, randomized experiment and then completed the perceiving and understanding emotion components of the Mayer-Salovey-Caruso Emotional Intelligence Test. In this test, emotion identification accuracy is based on agreement with a normative sample. As expected, participants administered intranasal oxytocin rated emotion in facial stimuli as expressing greater emotional intensity than those given a placebo. Consequently, accurate identification of emotion in faces, based on agreement with a normative sample, was impaired in the oxytocin group relative to placebo. No such effect was observed for tests using nonsocial stimuli. The results are consistent with the hypothesis that intranasal oxytocin enhances the salience of social stimuli in the environment, but not nonsocial stimuli. The present findings support a growing literature showing that the effects of intranasal oxytocin on social cognition can be negative under certain circumstances, in this case promoting "oversensitivity" to emotion in faces in healthy people.

  8. Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine

    Science.gov (United States)

    Tasaniyananda, Natt; Chaisri, Urai; Tungtrongchitr, Anchalee; Chaicumpa, Wanpen; Sookrung, Nitat

    2016-01-01

    Cats (Felis domesticus) are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen) in comparison with the vaccine made of crude cat hair extract (cCE). BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L)-entrapped native Fel d 1 (L-nFD1), L-cCE), or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions) towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35) and Treg (up-regulation of IL-10 and TGF-β). In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients. PMID:26954254

  9. Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine.

    Directory of Open Access Journals (Sweden)

    Natt Tasaniyananda

    Full Text Available Cats (Felis domesticus are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen in comparison with the vaccine made of crude cat hair extract (cCE. BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L-entrapped native Fel d 1 (L-nFD1, L-cCE, or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35 and Treg (up-regulation of IL-10 and TGF-β. In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients.

  10. Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: An open trial.

    OpenAIRE

    Scantamburlo, Gabrielle; Hansenne, Michel; Geenen, Vincent; Legros, Jean-Jacques; Ansseau, Marc

    2015-01-01

    The aim of this open trial was to assess the antidepressant/anxiolytic effects of oxytocin used as an adjunct to antidepressant in treatment-resistant depression. Fourteen patients, who have not responded to 40mg of escitalopram, received intranasal synthetic oxytocin during 4 weeks, in association with antidepressant. This is the first open trial study suggesting OT in association with escitalopram significantly reduced scores on Hamilton Depression Rating Scale. Peer reviewed

  11. INTRANASAL DELIVERY OF NERVE GROWTH FACTOR TO PROTECT THE CENTRAL NERVOUS SYSTEM AGAINST ACUTE CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    Hong-mei Zhao; Xin-feng Liu; Xiao-wei Mao; Chun-fu Chen

    2004-01-01

    Objective To confirmed reliability and feasibility of intranasal nerve growth factor (NGF) bypassing the blood-brain barrier and its potential neuroprotective effects on acute cerebral ischemia.Methods (1) To assay NGF concentrations in different brain regions after middle cerebral artery occlusion (MCAO).Rats were randomly divided into intranasal (IN) NGF, intravenous (Ⅳ) NGF, and untreated group (n =4). The concentrations of NGF of different brain regions in the three groups after MCAO were measured by ELISA. (2) To observe neuroprotective action of NGF on focal cerebral ischemic damage. Rats were randomly assigned to 4 groups: IN vehicle, IN NGF,Ⅳ vehicle, Ⅳ NGF (n = 8). Treatment was initiated 30 minutes after onset of MCAO and given again 24 hours later. Three neurologic behavioral tests were performed 24 and 48 hours following onset of MCAO. Corrected infarct volumes were determined 48 hours after onset of MCAO.Results The olfactory bulb in IN NGF group obtained the highest concentration (3252 pg/g) of NGF among all regions, followed by the hippocumpus. The NGF concentrations in the olfactory bulb and hippocampus in IN NGF group were markedly higher than that in Ⅳ NGF and control groups. The infarct volume in IN NGF group was markedly reduced by 38.8% compared with IN vehicle group. IN NGF group vestibulum function markedly improved compared with IN vehicle group at 24 and 48 hours after onset of MCAO (P24h = 0.02 and P48h = 0.04, respectively).Conclusion Intranasal NGF could pass through the blood-brain barrier, reach the central nervous system, reduce infarct volume, and improve neurologic function in rats following MCAO. Intranasal delivery of NGF may be a promising treatment for stroke.

  12. Effects of recombinant IL-17F intranasal inoculation against Streptococcus pneumoniae infection in a murine model.

    Science.gov (United States)

    Chen, Ling; Guo, Sheng; Wu, Liangxia; Hao, Chunli; Xu, Wanting; Zhang, Jianhua

    2015-01-01

    Interleukin-17F (IL-17F) is an important member of IL-17 cytokine family, which plays important roles in host defense against microbial infections. Streptococcus pneumoniae is a common pathogen associated with several invasive and noninvasive pneumococcal diseases, and mucosal immune response plays crucial roles in defenses against pneumococcal infection. Thus, intranasal inoculation may be an alternative approach against pneumococci. In this study, BALB/c mice were intranasally inoculated with recombinant IL-17F (rIL-17F) prior to S. pneumoniae (American Type Culture Collection 6303, serotype 3) infection. As compared with the control group, numbers of total leukocyte, neutrophil, and macrophage in lungs were significantly increased in mice inoculated with rIL-17F. The levels of macrophage inflammatory protein 1α (MIP-1α), MIP-2β, and interferon γ were significantly increased in bronchoalveolar lavage fluid and culture supernatant of splenocytes from mice inoculated with rIL-17F. rIL-17F inoculation also significantly elevated β-defensin-2 expression in lung tissues. Furthermore, compared with S. pneumoniae infection group, rIL-17F inoculation prior to infection significantly reduced S. pneumoniae colonization in lungs. These findings demonstrated that rIL-17F intranasal inoculation strengthened host defense against pneumococci, which may be developed to prevent pneumococcal infection. PMID:25196250

  13. Intranasal Delivery of Camptothecin-Loaded Tat-Modified Nanomicells for Treatment of Intracranial Brain Tumors

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    Yuuki Takashima

    2012-10-01

    Full Text Available The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials. In this study, we evaluated a nose-to-brain delivery system for brain tumor therapy. We nasally administered the anti-tumor drug camptothecin (CPT in solution and in methoxy poly(ethylene glycol (MPEG/poly(e-caprolactone (PCL amphiphilic block copolymers (MPEG-PCL and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG-PCL-Tat didn’t show any cytotoxicity, even at high concentrations (2 mmol/mL. CPT-loaded MPEG-PCL-Tat micelles significantly prolonged the median survival of rats. These results indicate that intranasal delivery of anti-cancer drugs with cell penetrating peptide-modified nanomicelles might be an effective therapy for brain tumors.

  14. Administration of bleomycin via the oropharyngeal aspiration route leads to sustained lung fibrosis in mice and rats as quantified by UTE-MRI and histology.

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    Christine Egger

    Full Text Available Pulmonary fibrosis can be experimentally induced in small rodents by bleomycin. The antibiotic is usually administered via the intratracheal or intranasal routes. In the present study, we investigated the oropharyngeal aspiration of bleomycin as an alternative route for the induction of lung fibrosis in rats and mice. The development of lung injury was followed in vivo by ultrashort echo time magnetic resonance imaging (UTE-MRI and by post-mortem analyses (histology of collagen, hydroxyproline determination, and qRT-PCR. In C57BL/6 mice, oropharyngeal aspiration of bleomycin led to more prominent lung fibrosis as compared to intranasal administration. Consequently, the oropharyngeal aspiration route allowed a dose reduction of bleomycin and, therewith, a model refinement. Moreover, the distribution of collagen after oropharyngeal aspiration of bleomycin was more homogenous than after intranasal administration: for the oropharyngeal aspiration route, fibrotic areas appeared all over the lung lobes, while for the intranasal route fibrotic lesions appeared mainly around the largest superior airways. Thus, oropharyngeal aspiration of bleomycin induced morphological changes that were more comparable to the human disease than the intranasal administration route did. Oropharyngeal aspiration of bleomycin led to a homogeneous fibrotic injury also in rat lungs. The present data suggest oropharyngeal aspiration of bleomycin as a less invasive means to induce homogeneous and sustained fibrosis in the lungs of mice and rats.

  15. Intranasal Delivery of Group B Meningococcal Native Outer Membrane Vesicle Vaccine Induces Local Mucosal and Serum Bactericidal Antibody Responses in Rabbits

    OpenAIRE

    Shoemaker, David R.; Saunders, Nancy B.; Brandt, Brenda L.; Moran, E. Ellen; LaClair, Andrew D.; Zollinger, Wendell D.

    2005-01-01

    We have previously shown that intranasal immunization of mice with meningococcal native outer membrane vesicles (NOMV) induces both a good local mucosal antibody response and a good systemic bactericidal antibody response. However, in the intranasal mouse model, some of the NOMV entered the lung and caused an acute granulocytic response. We therefore developed an alternate animal model using the rabbit. This model reduces the probability of lung involvement and more closely mimics intranasal ...

  16. Effects of Oxytocin Administration on the Response of Piglets to Weaning

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    Jean-Loup Rault

    2015-07-01

    Full Text Available Weaning is often an abrupt and stressful process. We studied the effects of administering oxytocin, subcutaneously or intranasally, on the ability of pigs to cope with weaning. On a commercial farm 144, 30 day-old pigs from 24 litters were used. On the day of weaning, one male and one female in each litter were administered one of three treatments: intranasal oxytocin (24 International Unit, subcutaneous oxytocin (10 International Unit per kg of body weight, or handled as a control. The pigs were placed in one of eight weaner pens, split by sex and with an equal representation of treatments. Data included body weight and growth, physiology (neutrophil:lymphocyte ratio, plasma cortisol, C-reactive protein and Tumor Necrosis Factor-α concentrations, and behavior (feeding, drinking, social behavior. Both oxytocin treatments tended to result in higher levels of mild aggression within groups (p = 0.08, specifically between oxytocin-administered and control pigs (subcutaneous to control p = 0.03; intranasal to control p = 0.10. Subcutaneously-administered pigs tended to frequent the feeder more often than intranasally-administered pigs (p < 0.10, with the latter having slightly lower body weight 38 days post-weaning (p = 0.03. However, acute oxytocin administration did not result in any noticeable physiological changes 4 or 28 h post-weaning. Hence, the use of a single administration of oxytocin prior to weaning in pigs is not recommended, at least not in the conditions studied here.

  17. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease.

    Science.gov (United States)

    Danielyan, Lusine; Beer-Hammer, Sandra; Stolzing, Alexandra; Schäfer, Richard; Siegel, Georg; Fabian, Claire; Kahle, Philipp; Biedermann, Tilo; Lourhmati, Ali; Buadze, Marine; Novakovic, Ana; Proksch, Barbara; Gleiter, Christoph H; Frey, William H; Schwab, Matthias

    2014-01-01

    administrations) to achieve functional improvement in these mouse models with intranasal microglia/macrophages and MSCs. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

  18. Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs

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    Sreerupa Challa

    2011-01-01

    Full Text Available Peptides corresponding to the foot-and-mouth disease virus VP1 G-H loop are capable of inducing neutralizing antibodies in some species but are considered relatively poor immunogens, especially at mucosal surfaces. However, intranasal administration of antigens along with the appropriate delivery vehicle/adjuvant has been shown to induce mucosal immune responses, and bacterial enterotoxins have long been known to be effective in this regard. In the current study, two different carrier/adjuvant approaches were used to augment mucosal immunity to the FMDV O1 BFS G-H loop epitope, in which the G-H loop was genetically coupled to the E. coli LT-B subunit and coexpressed with the LTA2 fragment (LTA2B-GH, or the nontoxic pseudomonas exotoxin A (ntPE was fused to LTA2B-GH at LT-A2 to enhance receptor targeting. Only guinea pigs that were inoculated intranasally with ntPE-LTA2B-GH and LTA2B-GH induced significant anti-G-H loop IgA antibodies in nasal washes at weeks 4 and 6 when compared to ovalbumin or G-H loop immunized animals. These were also the only groups that exhibited G-H loop-specific antigen-secreting cells in the nasal mucosa. These data demonstrate that fusion of nonreplicating antigens to LTA2B and ntPE-LTA2B has the potential to be used as carriers/adjuvants to induce mucosal immune responses against infectious diseases.

  19. Team research methods for studying intranasal heroin use and its HIV risks.

    Science.gov (United States)

    Ouellet, L J; Wiebel, W W; Jimenez, A D

    1995-01-01

    qualitative methods were combined to a degree uncommon in social science research. While many of these research groups have since disbanded, COIP was fortunate enough to remain in operation. The authors have described how they assembled a field research team composed of COIP members that combined ethnographers with selected indigenous staff to address a particular problem--new heroin use and its implications for HIV/AIDS. The goals the researchers set for the study would have been impossible for a single ethnographer or for a survey research team acting alone: to discern potential trends in new heroin use (though researchers were limited to studying mostly poor people); to develop fairly deep understandings regarding the study's central concerns (e.g., factors likely to influence the decision to inject heroin); and to quickly and economically collect data that were useful and valid. The authors note that all members of the research team had a host of other responsibilities; thus, this study was conducted as a sort of side job, that is, researchers had to fit it in when time and circumstances allowed. Altogether, the team field research method as applied to new heroin use in Chicago has enabled the research team to quickly and economically generate data that can be used to inform public policy on this issue (Ouellet et al. 1993; Ouellet et al., submitted). The authors believe that they can make a reasonably strong case for the following: New heroin use deserves greater study--the prevalence and incidence of use are probably sufficient to form a new cohort of potentially longtime users. New users are most likely to be found where major heroin street drug markets operate. Among youth there is a need for education about heroin--current users often report being surprised by heroin's addictiveness. Intranasal use is the predominant form of heroin administration among young, new users, and there is strong peer pressure against injection. Experimentation with injection, how PMID

  20. Intranasal inoculation of white-tailed deer (Odocoileus virginianus with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay.

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    Tracy A Nichols

    Full Text Available Chronic wasting disease (CWD, the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte, lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.

  1. Ancillary therapy of intranasal T-LysYal® for patients with allergic, non-allergic, and mixed rhinitis.

    Science.gov (United States)

    Gelardi, M; Taliente, S; Fiorella, M L; Quaranta, N; Ciancio, G; Russo, C; Mola, P; Ciofalo, A; Zambetti, G; Caruso Armone, A; Cantone, E; Ciprandi, G

    2016-01-01

    Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction. Non-allergic rhinitis (NAR) is characterized by a non-IgE-mediated pathogenesis. Frequently, patients have the two disorders associated: such as mixed rhinitis (MR). Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert anti-inflammatory and immune-modulating activities. Recently, an intranasal HA formulation was proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (rinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 89 patients (48 males and 41 females, mean age 36.3±7.1 years) with AR, NAR, and MR. Patients were treated with intranasal T-LysYal® or isotonic saline solution as adjunctive therapy to nasal corticosteroid and oral antihistamine for 4 weeks. Patients were visited at baseline, after treatment and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells. In conclusion, the present study demonstrates that intranasal T-LysYal® is able, as ancillary therapy, to significantly improve patients with AR, NAR, and MR, and its effect is long lasting. PMID:27049100

  2. Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988)

    International Nuclear Information System (INIS)

    Objective: To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Design: Retrospective study. Animals: Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Procedure: Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Results: Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Clinical Implications: Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia

  3. Optimal time for intranasal splint removal after septoplasty: a prospective clinical study.

    Science.gov (United States)

    Ozdogan, Fatih; Ozel, Halil Erdem; Esen, Erkan; Yuce, Turgut; Eyisarac, Saban; Genc, Selahattin; Selcuk, Adin

    2016-10-01

    To investigate the effect of intranasal splint removal time on patient comfort and possible complications after septoplasty. One hundred and nine patients who had septoplasty operations were included in this study. The patients were divided into three groups. In the 1st group (n = 36), splints were removed on the 3rd day after septoplasty; in the 2nd group (n = 36), splints were removed on the 5th day; and in the 3rd group (n = 37), splints were removed on the 7th day. Pain and nasal fullness were evaluated with visual analog scale. Synechia, perforation, hematoma, infection and hemorrhage were recorded after the removal of the splints (postoperative 1, 8 and 24 weeks). For the 1st, 2nd, and 3rd groups, respectively, pain score was 1.96, 2.67, and 2.67; and nasal fullness score was 6.23, 6.04, and 5.48. Nasal synechia was detected in two patients in the 1st group and in one patient in the 2nd group. Early hemorrhage was detected in two patients in the 1st group and one patient in the 3rd group. Infection, septal perforation and hematoma were detected in three patients in the 1st group. There was no difference in hemorrhage, hematoma, synechia and perforation rates between the three groups. There are various opinions in the literature about the ideal removal time of intranasal tampons after septoplasty, but there is no consensus on this topic. Our study shows that removal time of intranasal splints has no effect on patient comfort or possible complications. PMID:27015667

  4. Management of nasal aspergillosis in a dog with a single, noninvasive intranasal infusion of clotrimazole

    International Nuclear Information System (INIS)

    An 11-year-old, spayed female keeshond was presented for unilateral epistaxis and serous nasal discharge of four weeks duration. Initial nasal radiographs, rhinoscopy, and histopathology suggested severe, destructive lymphoplasmacytic rhinitis. The patient deteriorated while receiving an anti-inflammatory dose of prednisone. A computed tomographic scan of the nose demonstrated a soft-tissue density in both the right nasal cavity and frontal sinus. Samples for histopathology obtained at surgery were diagnostic for nasal aspergillosis. All clinical signs resolved with a single, noninvasive infusion of intranasal clotrimazole and a four-week course of oral itraconazole

  5. Locus coeruleus response to single-prolonged stress and early intervention with intranasal neuropeptide Y.

    Science.gov (United States)

    Sabban, Esther L; Laukova, Marcela; Alaluf, Lishay G; Olsson, Emelie; Serova, Lidia I

    2015-12-01

    Dysregulation of the central noradrenergic system is a core feature of post-traumatic stress disorder (PTSD). Here, we examined molecular changes in locus coeruleus (LC) triggered by single-prolonged stress (SPS) PTSD model at a time when behavioral symptoms are manifested, and the effect of early intervention with intranasal neuropeptide Y (NPY). Immediately following SPS stressors, male SD rats were administered intranasal NPY (SPS/NPY) or vehicle (SPS/V). Seven days later, TH protein, but not mRNA, was elevated in LC only of the SPS/V group. Although 90% of TH positive cells expressed GR, its levels were unaltered. Compared to unstressed controls, LC of SPS/V, but not SPS/NPY, expressed less Y2 receptor mRNA with more CRHR1 mRNA in subset of animals, and elevated corticotropin-releasing hormone (CRH) in central nucleus of amygdala. Following testing for anxiety on elevated plus maze (EPM), there were significantly increased TH, DBH and NPY mRNAs in LC of SPS-treated, but not previously unstressed animals. Their levels highly correlated with each other but not with behavioral features on EPM. Thus, SPS triggers long-term noradrenergic activation and higher sensitivity to mild stressors, perhaps mediated by the up-regulation influence of amygdalar CRH input and down-regulation of Y2R presynaptic inhibition in LC. Results also demonstrate the therapeutic potential of early intervention with intranasal NPY for traumatic stress-elicited noradrenergic impairments. Single-prolonged stress (SPS)-triggered long-term changes in the locus coeruleus/norepinephrine (LC/NE) system with increased tyrosine hydroxylase (TH) protein and CRH receptor 1(CRHR1) mRNA and lower neuropeptide Y receptor 2 (Y2R) mRNA levels as well as elevated corticotropin-releasing hormone (CRH) in the central nucleus of amygdala (CeA) that were prevented by early intervention with intranasal neuropeptide Y (NPY). SPS treatment led to increased sensitivity of LC to mild stress of elevated plus maze

  6. Locus coeruleus response to single-prolonged stress and early intervention with intranasal neuropeptide Y.

    Science.gov (United States)

    Sabban, Esther L; Laukova, Marcela; Alaluf, Lishay G; Olsson, Emelie; Serova, Lidia I

    2015-12-01

    Dysregulation of the central noradrenergic system is a core feature of post-traumatic stress disorder (PTSD). Here, we examined molecular changes in locus coeruleus (LC) triggered by single-prolonged stress (SPS) PTSD model at a time when behavioral symptoms are manifested, and the effect of early intervention with intranasal neuropeptide Y (NPY). Immediately following SPS stressors, male SD rats were administered intranasal NPY (SPS/NPY) or vehicle (SPS/V). Seven days later, TH protein, but not mRNA, was elevated in LC only of the SPS/V group. Although 90% of TH positive cells expressed GR, its levels were unaltered. Compared to unstressed controls, LC of SPS/V, but not SPS/NPY, expressed less Y2 receptor mRNA with more CRHR1 mRNA in subset of animals, and elevated corticotropin-releasing hormone (CRH) in central nucleus of amygdala. Following testing for anxiety on elevated plus maze (EPM), there were significantly increased TH, DBH and NPY mRNAs in LC of SPS-treated, but not previously unstressed animals. Their levels highly correlated with each other but not with behavioral features on EPM. Thus, SPS triggers long-term noradrenergic activation and higher sensitivity to mild stressors, perhaps mediated by the up-regulation influence of amygdalar CRH input and down-regulation of Y2R presynaptic inhibition in LC. Results also demonstrate the therapeutic potential of early intervention with intranasal NPY for traumatic stress-elicited noradrenergic impairments. Single-prolonged stress (SPS)-triggered long-term changes in the locus coeruleus/norepinephrine (LC/NE) system with increased tyrosine hydroxylase (TH) protein and CRH receptor 1(CRHR1) mRNA and lower neuropeptide Y receptor 2 (Y2R) mRNA levels as well as elevated corticotropin-releasing hormone (CRH) in the central nucleus of amygdala (CeA) that were prevented by early intervention with intranasal neuropeptide Y (NPY). SPS treatment led to increased sensitivity of LC to mild stress of elevated plus maze

  7. Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: Role of docosahexaenoic acid.

    Science.gov (United States)

    Shinde, Rajshree L; Bharkad, Gopal P; Devarajan, Padma V

    2015-10-01

    Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection are reported. MEs prepared by simple solution exhibited a globule size 95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (P<0.05) suggested the role of DHA in aiding nose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10ng/mL) DHA ME in vitro on Taenia solium cysts was confirmed by complete ALP inhibition and disintegration of cysts at 96h. Considering that the brain concentration at 24h was 1400±160.1ng/g (ABZ-SO) and 120±35.2ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery.

  8. Pharmacokinetics of Intranasal Scopolamine Gel Formation During Antiorthostatic Bedrest - A Microgravity Analog

    Science.gov (United States)

    Lakshmi, Putcha; Singh, R. P.; Crady, V. A.; Derendorf, H.

    2011-01-01

    Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  9. Treatment of renal colic by desmopressin intranasal spray and diclofenac sodium.

    Science.gov (United States)

    el-Sherif, A E; Salem, M; Yahia, H; al-Sharkawy, W A; al-Sayrafi, M

    1995-05-01

    The vasopressin analogue, 1-desamino-8-arginine vasopressin (desmopressin), is a potent antidiuretic without the pressor effects of vasopressin. A total of 18 patients with acute renal colic due to stone disease received 40 microgramsf1p4mopressin intranasal spray with encouraging results. There was a significant decrease in the colic pain intensity from an initial mean visual analogue score of 67 +/- 17 mm. to 39 +/- 36 mm. within 30 minutes (p renal colic is uncertain. At the peripheral level, desmopressin may alleviate the acute renal colic through its potent antidiuretic effect or by relaxing the renal pelvic and ureteral smooth muscles. The central analgesic effect of desmopressin by stimulating the release of the hypothalamic beta-endorphin is proposed. We conclude that intranasal desmopressin spray can be used successfully in the treatment of renal colic. It may also replace prostaglandin synthetase inhibitors in treating renal colic with the advantage of avoiding the potential side effects. Further studies are needed to investigate whether the combination of desmopressin with analgesics or spasmolytic drugs offers competitive results compared with those achieved by prostaglandin synthetase inhibitors in the treatment of renal colic. PMID:7714949

  10. Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes.

    Science.gov (United States)

    Every, Alison L; Kramer, David R; Mannering, Stuart I; Lew, Andrew M; Harrison, Leonard C

    2006-04-15

    Insulin, an autoantigen in type 1 diabetes, when administered mucosally to diabetes-prone NOD mice induces regulatory T cells (T(reg)) that protect against diabetes. Compared with protein, Ag encoded as DNA has potential advantages as a therapeutic agent. We found that intranasal vaccination of NOD mice with plasmid DNA encoding mouse proinsulin II-induced CD4+ T(reg) that suppressed diabetes development, both after adoptive cotransfer with "diabetogenic" spleen cells and after transfer into NOD mice given cyclophosphamide to accelerate diabetes onset. In contrast to prototypic CD4+ CD25+ T(reg), CD4+ T(reg) induced by proinsulin DNA were both CD25+ and CD25- and not defined by markers such as glucocorticoid-induced TNFR-related protein (GITR), CD103, or Foxp3. Intriguingly, despite induction of T(reg) and reduced islet inflammation, diabetes incidence in proinsulin DNA-treated mice was unchanged. However, diabetes was prevented when DNA vaccination was performed under the cover of CD40 ligand blockade, known to prevent priming of CTL by mucosal Ag. Thus, intranasal vaccination with proinsulin DNA has therapeutic potential to prevent diabetes, as demonstrated by induction of protective T(reg), but further modifications are required to improve its efficacy, which could be compromised by concomitant induction of pathogenic immunity. PMID:16585551

  11. Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations

    Institute of Scientific and Technical Information of China (English)

    Jing-yi ZHAO; Yang LU; Shou-ying DU; Xiao SONG; Jie BAI; Yue WANG

    2012-01-01

    Borneol,a monoterpenoid alcohol,is used widely,particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine.In order to understand the blood and brain pharmacokinetics after intravenous,intranasal,or oral administration and to investigate the superiority and feasibility of intranasal administration,a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol.Blood samples and brain were collected from mice at 1,3,5,10,20,30,60,90,and 120 min after intravenous,intranasal,or oral administration of borneol at a dosage of 30.0 mg/kg.Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane.The pharmacokinetic parameters were calculated by the software of Kinetica.The calibration curves were linear in the range of 0.11-84.24 μg/ml and 0.16-63.18 μg/g for borneol in plasma and brain,respectively.The methodological and extraction recoveries were both in the range of 85%-115%.The intra-day and inter-day variabilities for plasma and brain samples were ≤5.00% relative standard deviation (RSD).The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%.The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%.The GC-FID method developed could be applied to determination and pharmacokinetic study.The borneol from injection was distributed and metabolized fast without absorption process.The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability.Nasal administration of borneol was quickly absorbed into the blood and brain,was easy to use and had a greater safety than infection,which makes it worthy of further development as an administration route for encephalopathy treatment.

  12. Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    2016-03-01

    Full Text Available Immunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV and human papillomaviruses (HPV. The kinetics and mechanisms of regulation of vaccine-induced adaptive T cell-mediated immune responses in FRT are less well defined. We present here evidence for intranasal delivery of the model antigen ovalbumin (OVA along with alpha-galactosylceramide adjuvant as a protein vaccine to induce significantly higher levels of antigen-specific effector and memory CD8+ T cells in the FRT, relative to other systemic and mucosal tissues. Antibody blocking of the CXCR3 receptor significantly reduced antigen-specific CD8+ T cells subsequent to intranasal delivery of the protein vaccine suggesting an important role for the CXCR3 chemokine-receptor signaling for T cell trafficking. Further, intranasal vaccination with an adenoviral vector expressing OVA or HIV-1 envelope was as effective as intramuscular vaccination for generating OVA- or ENV-specific immunity in the FRT. These results support the application of the needle-free intranasal route as a practical approach to delivering protein as well as DNA/virus vector-based vaccines for efficient induction of effector and memory T cell immunity in the FRT.

  13. Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in Murine Type I Diabetic Encephalopathy

    Science.gov (United States)

    Francis, George J.; Martinez, Jose A.; Liu, Wei Q.; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I.; Glazner, Gordon; Hanson, Leah R.; Frey, William H., II; Toth, Cory

    2008-01-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential…

  14. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units. This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation and low to moderate doses (103 to 106 plaque forming units of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common influenza

  15. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection

    Science.gov (United States)

    Marriott, Anthony C.; Dennis, Mike; Kane, Jennifer A.; Gooch, Karen E.; Hatch, Graham; Sharpe, Sally; Prevosto, Claudia; Leeming, Gail; Zekeng, Elsa-Gayle; Staples, Karl J.; Hall, Graham; Ryan, Kathryn A.; Bate, Simon; Moyo, Nathifa; Whittaker, Catherine J.; Hallis, Bassam; Silman, Nigel J.; Lalvani, Ajit; Wilkinson, Tom M.; Hiscox, Julian A.; Stewart, James P.; Carroll, Miles W.

    2016-01-01

    Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections. PMID

  16. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

    Science.gov (United States)

    Marriott, Anthony C; Dennis, Mike; Kane, Jennifer A; Gooch, Karen E; Hatch, Graham; Sharpe, Sally; Prevosto, Claudia; Leeming, Gail; Zekeng, Elsa-Gayle; Staples, Karl J; Hall, Graham; Ryan, Kathryn A; Bate, Simon; Moyo, Nathifa; Whittaker, Catherine J; Hallis, Bassam; Silman, Nigel J; Lalvani, Ajit; Wilkinson, Tom M; Hiscox, Julian A; Stewart, James P; Carroll, Miles W

    2016-01-01

    Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections. PMID

  17. Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection against Naegleria fowleri Meningoencephalitis

    Science.gov (United States)

    Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A.; López-Revilla, Rubén; Reséndiz-Albor, Aldo A.; Moreno-Fierros, Leticia

    2004-01-01

    Cry1Ac protoxin has potent mucosal and systemic adjuvant effects on antibody responses to proteins or polysaccharides. In this work, we examined whether Cry1Ac increased protective immunity against fatal Naegleria fowleri infection in mice, which resembles human primary amoebic meningoencephalitis. Higher immunoglobulin G (IgG) than IgA anti-N. fowleri responses were elicited in the serum and tracheopulmonary fluids of mice immunized by the intranasal or intraperitoneal route with N. fowleri lysates either alone or with Cry1Ac or cholera toxin. Superior protection against a lethal challenge with 5 × 104 live N. fowleri trophozoites was achieved for immunization by the intranasal route. Intranasal immunization of N. fowleri lysates coadministered with Cry1Ac increased survival to 100%; interestingly, immunization with Cry1Ac alone conferred similar protection to that achieved with amoebal lysates alone (60%). When mice intranasally immunized with Cry1Ac plus lysates were challenged with amoebae, both IgG and IgA mucosal responses were rapidly increased, but only the increased IgG response persisted until day 60 in surviving mice. The brief rise in the level of specific mucosal IgA does not exclude the role that this isotype may play in the early defense against this parasite, since higher IgA responses were detected in nasal fluids of mice intranasally immunized with lysates plus either Cry1Ac or cholera toxin, which, indeed, were the treatments that provided the major protection levels. In contrast, serum antibody responses do not seem to be related to the protection level achieved. Both acquired and innate immune systems seem to play a role in host defense against N. fowleri infection, but further studies are required to elucidate the mechanisms involved in protective effects conferred by Cry1Ac, which may be a valuable tool to improve mucosal vaccines. PMID:15271892

  18. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

    Directory of Open Access Journals (Sweden)

    Mohapatra Shyam S

    2006-08-01

    Full Text Available Abstract Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in

  19. Pharmacokinetics of Intranasal Scopolamine Gel Formulation During Antiorthostatic Bed Rest, a Microgravity Analog

    Science.gov (United States)

    Singh, Rajendra P.; Daniels, Vernie R.; Crady, Camille J.; Derendorf, H.; Putcha, L.

    2011-01-01

    Statement of Purpose, Innovation or Hypothesis: Space Motion sickness (SMS) is a long-standing problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is frequently used for the treatment of motion sickness (MS), and is available as transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability, thus allowing precise and reduced dosing in addition to offering rescue and treatment options. An intranasal gel dosage formulation of scopolamine (INSCOP) was developed and pharmacokinetics (PK) and bioavailability were determined in clinical trials with human subjects under IND guidelines.Description of Methods and Materials: The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostaticbed rest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 mg and 0.4 mg doses of INSCOP during AMB and ABR in a 4-way crossover design.Data and Results: Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose, Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration-versus-time curve (AUC) during ABR after the 0.4 mg dose.Interpretation, Conclusion or Significance: The difference in AUC and Cls at the higher (0.4 mg) but not the lower dose (0.2 mg) during ABR suggests that ABR may affect metabolism and/or clearance of INSCOP at higher doses . These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  20. Protection of inactive intranasal ántrax vaccine to Bacillus anthracis infection

    Directory of Open Access Journals (Sweden)

    Adin Priadi

    2010-06-01

    Full Text Available Ánthrax is an endemic zoonotic disease distributed in many parts of Indonesia. Although vaccination program has been implemented in many areas, cases are still frequently reported. Farmers are reluctant to vaccinate their livestock since spore vaccine used in the field often cause side effects and death of the animals. To overcome this problem, an inactive vaccine composes of Bacillus anthracis toxins, cell wall and capsule subunits was developed. B. anthracis Sterne strain (34F2 was selected to produce toxins and cell walls. Local Bacillus anthracis isolated from Citaringgul was used to produce capsule as the Polymerase Chain Reaction (PCR revealed that this isolate poses cap gene encoding for capsule. Two vaccines compose of 15 μg toxoid, 30 μg of capsule, 15 μg of cell wall and 30 μg toxoid, 60 μg of capsule, 15 μg of cell walls were designated as vaccine I and vaccine II respectively. For each experiment, 10 mice were nasally immunized by placing 5 μl of vaccine into each nare 3 times at 2-week intervals. A group of 10 mice were unvaccinated and used as control. Blood was collected fortnightly to monitor antibody responses. All mice were challenged with 2 x 105 B. anthracis Sterne spores injected subcutaneously two weeks after the last vaccination. Two weeks after vaccination of antibodies to B. anthracis toxin, capsule and cell wall were detected in dot-blot assay. Mice that were immunised intranasally with chitosan adjuvanted vaccine developed high IgG responses in sera as detected by ELISA, and the response was dose dependent. Vaccine II gave better response than vaccine I. Vaccine I and II protected mice from challenge at a rate of 60 and 80% respectively. This results showed that intranasal B. anthracis vaccine composes of toxin, capsule and cell wall with chitosan as an adjuvant gave a good protection against B. anthracis Sterne spores challenge in mice.

  1. Administrating Solr

    CERN Document Server

    Mohan, Surendra

    2013-01-01

    A fast-paced, example-based guide to learning how to administrate, monitor, and optimize Apache Solr.""Administrating Solr"" is for developers and Solr administrators who have a basic knowledge of Solr and who are looking for ways to keep their Solr server healthy and well maintained. A basic working knowledge of Apache Lucene is recommended, but this is not mandatory.

  2. Intranasal application of Epstein-Barr virus/lipoplex to abrogate eosinophillia in murine model of allergic rhinitis

    Institute of Scientific and Technical Information of China (English)

    HAN De-min; ZHOU Bing; WANG Tong; WANG Xiang-dong; FAN Er-zhong

    2006-01-01

    Background Currently anti-inflammatory therapy with steroids for allergic rhinitis need long-term repeated administration, although it is effective. Gene therapy is being suggested to substitute it. The aim of this study was to investigate nonviral vector mediated exogenous gene expression in COS-7 cells in vitro and the effect of intranasal mouse interleukin (mIL)-12 transgene expression on allergen induced eosinophil infiltration of nasal mucosa in a murine model of allergic rhinitis.Methods In vitro COS-7 cells were infected with Epstein-Barr virus (EBV)/lipoplex. The expression of IL-12 p70 in cell culture supernatant was examined by enzyme-linked immunosorbent assay (ELISA). In mice with ovalbumin (OVA) induced allergic rhinitis, EBV/lipoplex was administered by nasal drops before OVA challenge once a day from day 1 to day 10. The expression of IL-12 mRNA and protein, the change of eosinophil count in nasal mucosa and serum total IgE were measured 24 hours after the last challenge.Results EBV/lipoplex could effectively transfect COS-7 cells. The expression of IL-12 p70 in cell culture supernatant was significantly more than in blank control. IL-12 via EBV plasmid vector transduction could be overexpressed in vivo. In pGEG.mIL-12 treated models, the nasal mucosa revealed a high level of widespread mIL-12 transduction by immunohistochemistry and in situ hybridization. Histological evaluation revealed marked suppression of eosinophil infiltration in nasal mucosa. The eosinophil count in allergic rhinitis group [(26.5±9.8)/high-power field (HPF)] was significantly increased over control group [(0.40±0.52)/HPF](F=56.94, P<0.01), while the count in IL-12 gene therapy group [(4.60±2.63)/HPF] was significantly less than that of allergic group (F=56.9, P<0.01). Serum total IgE between in gene therapy mice [(88.83±6.71) ng/ml]and allergic rhinitis mice [(103.1 ± 5.7) ng/ml] showed a significant difference (F=1216, P<0.05).Conclusions Nonviral EBV plasmid

  3. Administrative Circulars

    CERN Multimedia

    Département des Ressources humaines

    2004-01-01

    Administrative Circular N° 2 (Rev. 2) - May 2004 Guidelines and procedures concerning recruitment and probation period of staff members This circular has been revised. It cancels and replaces Administrative Circular N° 2 (Rev. 1) - March 2000. Administrative Circular N° 9 (Rev. 3) - May 2004 Staff members contracts This circular has been revised. It cancels and replaces Administrative Circular N° 9 (Rev. 2) - March 2000. Administrative Circular N° 26 (Rev. 4) - May 2004 Procedure governing the career evolution of staff members This circular has also been revised. It Administrative Circulars Administrative Circular N° 26 (Rev. 3) - December 2001 and brings up to date the French version (Rev. 4) published on the HR Department Web site in January 2004. Operational Circular N° 7 - May 2004 Work from home This circular has been drawn up. Operational Circular N° 8 - May 2004 Dealing with alcohol-related problems...

  4. Subcutaneous Allergic Sensitization to Protease Allergen Is Dependent on Mast Cells but Not IL-33: Distinct Mechanisms between Subcutaneous and Intranasal Routes.

    Science.gov (United States)

    Kamijo, Seiji; Suzuki, Mayu; Hara, Mutsuko; Shimura, Sakiko; Ochi, Hirono; Maruyama, Natsuko; Matsuda, Akira; Saito, Hirohisa; Nakae, Susumu; Suto, Hajime; Ichikawa, Saori; Ikeda, Shigaku; Ogawa, Hideoki; Okumura, Ko; Takai, Toshiro

    2016-05-01

    Protease activity of papain, a plant-derived occupational allergen homologous to mite major allergens, is essential to IgE/IgG1 production and lung eosinophilia induced by intranasal papain administration in mice, and IL-33 contributes to these responses. In this work, we investigate skin and Ab responses induced by s.c. papain administration into ear lobes and responses induced by subsequent airway challenge with papain. Subcutaneous papain injection induced swelling associated with increased epidermal thickness, dermal inflammation, serum IgE/IgG1 responses, and Th2 cytokine production in draining lymph node cells restimulated in vitro. These responses were markedly less upon s.c. administration of protease inhibitor-treated papain. Results obtained by using mast cell-deficient mice and reconstitution of tissue mast cells suggested the contribution of mast cells to papain-specific IgE/IgG1 responses and eosinophil infiltration. The responses were equivalent between wild-type and IL-33(-/-) mice. After the subsequent airway challenge, the s.c. presensitized wild-type mice showed more severe lung eosinophilia than those without the presensitization. The presensitized IL-33(-/-) mice showed modest lung eosinophilia, which was absent without the presensitization, but its severity and IgE boost by the airway challenge were markedly less than the presensitized wild-type mice, in which protease activity of inhaled papain contributed to the responses. The results suggest that mechanisms for the protease-dependent sensitization differ between skin and airway and that cooperation of mast cell-dependent, IL-33-independent initial sensitization via skin and protease-induced, IL-33-mediated mechanism in re-exposure via airway to protease allergens maximizes the magnitude of the transition from skin inflammation to asthma in natural history of progression of allergic diseases. PMID:27001956

  5. Safety and immunogenicity of an intranasal Sendai virus-based human parainfluenza virus type 1 vaccine in 3- to 6-year-old children.

    Science.gov (United States)

    Adderson, Elisabeth; Branum, Kristen; Sealy, Robert E; Jones, Bart G; Surman, Sherri L; Penkert, Rhiannon; Freiden, Pamela; Slobod, Karen S; Gaur, Aditya H; Hayden, Randall T; Allison, Kim; Howlett, Nanna; Utech, Jill; Allay, Jim; Knight, James; Sleep, Susan; Meagher, Michael M; Russell, Charles J; Portner, Allen; Hurwitz, Julia L

    2015-03-01

    Human parainfluenza virus type 1 (hPIV-1) is the most common cause of laryngotracheobronchitis (croup), resulting in tens of thousands of hospitalizations each year in the United States alone. No licensed vaccine is yet available. We have developed murine PIV-1 (Sendai virus [SeV]) as a live Jennerian vaccine for hPIV-1. Here, we describe vaccine testing in healthy 3- to 6-year-old hPIV-1-seropositive children in a dose escalation study. One dose of the vaccine (5 × 10(5), 5 × 10(6), or 5 × 10(7) 50% egg infectious doses) was delivered by the intranasal route to each study participant. The vaccine was well tolerated by all the study participants. There was no sign of vaccine virus replication in the airway in any participant. Most children exhibited an increase in antibody binding and neutralizing responses toward hPIV-1 within 4 weeks from the time of vaccination. In several children, antibody responses remained above incoming levels for at least 6 months after vaccination. Data suggest that SeV may provide a benefit to 3- to 6-year-old children, even when vaccine recipients have preexisting cross-reactive antibodies due to previous exposures to hPIV-1. Results encourage the testing of SeV administration in young seronegative children to protect against the serious respiratory tract diseases caused by hPIV-1 infections.

  6. Assessing the Subjective and Physiological Effects of Intranasally Administered Crushed Extended-Release Morphine Formulations with and without a Sequestered Naltrexone Core in Recreational Opioid Users

    Directory of Open Access Journals (Sweden)

    Beatrice Setnik

    2013-01-01

    Full Text Available OBJECTIVE: To evaluate the pharmacodynamic (PD effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN capsules compared with controlled-release morphine sulfate (MS and placebo when crushed and administered intranasally.

  7. Intranasal Immunization of Guinea Pigs with an Immunodominant Foot-and-Mouth Disease Virus Peptide Conjugate Induces Mucosal and Humoral Antibodies and Protection against Challenge†

    OpenAIRE

    Fischer, D.; Rood, D.; Barrette, R. W.; Zuwallack, A.; Kramer, E.; Brown, F.; Silbart, L. K.

    2003-01-01

    Guinea pigs immunized intranasally with a keyhole limpet hemocyanin-linked peptide, corresponding to the prominent G-H loop of the VP1 protein of foot-and-mouth disease virus, raised substantial levels of antipeptide and virus-neutralizing antibodies in sera and of peptide-specific secretory immunoglobulin A in nasal secretions. In groups of animals immunized intranasally without adjuvant, 86 percent were fully protected upon challenge with homotypic virus. Surprisingly, animals given the pep...

  8. Intranasal Immune Challenge Induces Sex-Dependent Depressive-Like Behavior and Cytokine Expression in the Brain

    OpenAIRE

    Tonelli, Leonardo H.; Holmes, Andrew; Teodor T. Postolache

    2007-01-01

    The association between activation of the immune system and mood disorders has been reported by several studies. However, the mechanisms by which the immune system affects mood are only partially understood. In the present study, we detected depressive-like behavior in a rat animal model which involves the induction of inflammation in the nasal cavities by intranasal (i.n.) instillation of bacterial lipopolysaccharides (LPS). Female rats showed depressive-like behavior as evidenced by the for...

  9. The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test

    OpenAIRE

    Christopher Cardoso; Ellenbogen, Mark A.; Anne-Marie Linnen; Ridha Joober

    2012-01-01

    Background : There is increasing evidence that oxytocin promotes empathy in humans. However, research on oxytocin and emotion recognition, a fundamental component of empathy, has yielded inconsistent results. Part of the problem is that studies have focused on limited, and varying, categories of emotional stimuli. Therefore, we investigated the effect of intranasal oxytocin on the identification of seven basic emotions (happiness, sadness, fear, excitement, surprise, disgust, and anger) using...

  10. Formulation, High Throughput In Vitro Screening and In Vivo Functional Characterization of Nanoemulsion-Based Intranasal Vaccine Adjuvants

    OpenAIRE

    Pamela T. Wong; Leroueil, Pascale R.; Smith, Douglas M.; Ciotti, Susan; Bielinska, Anna U.; Janczak, Katarzyna W.; Mullen, Catherine H.; Groom, Jeffrey V.; Taylor, Erin M; Passmore, Crystal; Makidon, Paul E.; O’Konek, Jessica J.; Myc, Andrzej; Hamouda, Tarek; Baker, James R.

    2015-01-01

    Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate ...

  11. Limited evidence for intranasal fentanyl in the emergency department and the prehospital setting--a systematic review

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Dahl, Jørgen Berg

    2013-01-01

    The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim...... of this systematic review was to evaluate the current evidence for the use of IN fentanyl in the emergency department (ED) and prehospital setting....

  12. Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis

    OpenAIRE

    Yasuyuki Noyama; Mitsuhiro Okano; Tazuko Fujiwara; Shin Kariya; Sei-ichiro Makihara; Takenori Haruna; Kengo Kanai; Takaya Higaki; Kazunori Nishizaki

    2016-01-01

    Background: Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. Methods: We designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outsi...

  13. One-year evaluation of combined treatment with an intranasal corticosteroid and montelukast for chronic rhinosinusitis associated with asthma

    International Nuclear Information System (INIS)

    Chronic rhinosinusitis associated with asthma is often difficult to treat effectively with intranasal corticosteroids alone. Thus, the aim of this study was to evaluate the effectiveness of combination treatment with an intranasal corticosteroid and a leukotriene-receptor antagonist (montelukast) in reducing the size of nasal polyps. The subjects of this study were 20 patients with chronic rhinosinusitis associated with adult-onset asthma, which was being treated with inhaled corticosteroids. All patients were treated with intranasal fluticasone propionate, 200 μg/day, and montelukast, 10 mg/day, for 1 year. The size of nasal polyps and the score of sinus shadows were assessed with nasal endoscopy and computed tomography (CT), respectively, before and after treatment. The peripheral blood eosinophil counts were also evaluated before and after treatment. Nasal polyps were significantly smaller after both 6 months (p<0.01) and 12 months of treatment (p<0.01) than before treatment. The decrease in the shadow score was statistically significant after both 6 months (p<0.01) and 12 months of treatment (p<0.01). Significant reductions in peripheral blood eosinophil counts were also seen after both 6 months (p<0.05) and 12 months of treatment (p<0.01). A significant correlation was found between the rate of change in the peripheral blood eosinophil count and that in the CT score after both 6 months (r=0.578, p=0.012) and 12 months (r=0.625, p=0.007). Combined treatment with intranasal fluticasone propionate and montelukast, for at least 1 year, is effective for chronic rhinosinusitis associated with adult-onset asthma. (author)

  14. Administrative Ecology

    Science.gov (United States)

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  15. One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT(ZCI) protects animals against pathogenic viral challenge.

    Science.gov (United States)

    Yu, Wenbo; Fang, Qing; Zhu, Weijun; Wang, Haibo; Tien, Po; Zhang, Linqi; Chen, Zhiwei

    2010-02-25

    To combat variola virus in bioterrorist attacks, it is desirable to develop a noninvasive vaccine. Based on the vaccinia Tiantan (VTT) strain, which was historically used to eradicate the smallpox in China, we generated a modified VTT (MVTT(ZCI)) by removing the hemagglutinin gene and an 11,944bp genomic region from HindIII fragment C2L to F3L. MVTT(ZCI) was characterized for its host cell range in vitro and preclinical safety and efficacy profiles in mice. Despite replication-competency in some cell lines, unlike VTT, MVTT(ZCI) did not cause death after intracranial injection or body weight loss after intranasal inoculation. MVTT(ZCI) did not replicate in mouse brain and was safe in immunodeficient mice. MVTT(ZCI) induced neutralizing antibodies via the intranasal route of immunization. One time intranasal immunization protected animals from the challenge of the pathogenic vaccinia WR strain. This study established proof-of-concept that the attenuated replicating MVTT(ZCI) may serve as a safe noninvasive smallpox vaccine candidate.

  16. Allogeneic cartilage used for skull base plasty in children with primary intranasal encephalomeningocele associated with cerebrospinal fluid rhinorrhea.

    Science.gov (United States)

    Parízek, J; Mĕrićka, P; Nĕmecek, S; Nĕmecková, J; Zemánková, M; Sercl, M; Häringová, M

    1996-03-01

    Three children with primary intranasal encephalomeningocele associated with cerebrospinal fluid rhinorrhea were operated on at the Department of Neurosurgery, Hradec Králové. In two children, aged 4 and 9.5 years, freeze-dried allogeneic costal cartilage was glued into the skull base defect. This plugging was covered up with deep frozen allogeneic fascia lata. In the third child, an only 1-year-old boy, after transection of the neck of the encephalomeningocele freeze-dried allogeneic dura mater was glued on extradurally and deep-frozen allogeneic fascia lata applied intradurally. The cerebrospinal fluid rhinorrhea ceased immediately after surgery. Spontaneous atrophy of the intranasal portion of the encephalomeningocele was demonstrated respectively 11, 1, and 7 years postoperatively on computed tomography. To evaluate cartilage healing histologically, the extracted allogeneic cartilage used for orbital roof plasty after 4 months was examined. The extent of spotty regressions represented about 7% of the tissue volume. It is stressed that, once diagnosed, intranasal encephalomeningocele associated with cerebrospinal fluid rhinorrhea should be operated on for prevention of meningitis as soon as possible. PMID:8697455

  17. Treatment of singultus following craniocerebral injury Intranasal cavity drip infusion versus Intramuscular injection of aminazine

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Craniocerebral injury always accompanies with singultus, while frequent singultus may cause increased intracranial pressure. Simultaneously, respiratory alkalosis and cerebral hypoxia induced by respiratory disorder may aggravate craniocerebral injury.OBJECTIVE: To observe the therapeutic effects of intranasal cavity drip infusion of aminazine and intramuscular injection on singultus following craniocerebral injury.DESIGN: Contrast observation.SETTING: Department ofNeurosurgery, Xi'an Aerospace General Hospital.PARTICIPANTS: A total of 102 patients with singultus following craniocerebral injury were selected from the Department of Neurosurgery, Xi'an Aerospace General Hospital from June 2001 to June 2006. Patients with craniocerebral injury were diagnosed with CT examination and randomly divided into nasal cavity medication group (n =62) and intramuscular injection group (n =40). There were 44 males and 18 females in the nasal cavity medication group and their mean age was (33±4) years; while, there were 26 males and 14 females in the intramuscular injection group and their mean age was (29±4) years. All patients and their relatives provided the confirmed consent.METHODS: Patients in the nasal cavity medication group were slowly dripped aminazine solution into bilateral nasal cavity with the dosage of 12.5 mg (0.5 mL). Patients who had no obvious effect or had mild improvement received the treatment once every 6 hours. The treatment was stopped if symptoms were also observed after the fifth medication. In addition, patients in the intramuscular injection group received intramuscular injection of 50 mg aminazine. Patients who had no obvious effect or had mild improvement received the treatment once every 6 hours. The treatment was changed if symptoms were also observed after the fifth medication.MAIN OUTCOME MEASURES: Therapeutic effects of different medications in the two groups.RESULTS: All 102 patients were involved in the final analysis. Effective

  18. Development and Evaluation of a Novel Intranasal Spray for the Delivery of Amantadine.

    Science.gov (United States)

    Lungare, Shital; Bowen, James; Badhan, Raj

    2016-03-01

    The aim of this study was to develop and characterize an intranasal delivery system for amantadine hydrochloride (AMT). Optimal formulations consisted of a thermosensitive polymer Pluronic® 127 and either carboxymethyl cellulose or chitosan which demonstrated gel transition at nasal cavity temperatures (34 ± 1°C). Rheologically, the loss tangent (Tan δ) confirmed a 3-stage gelation phenomena at 34 ± 1°C and non-Newtonian behavior. Storage of optimized formulation carboxymethyl cellulose and optimal formulation chitosan at 4°C for 8 weeks resulted in repeatable release profiles at 34°C when sampled, with a Fickian mechanism earlier on but moving toward anomalous transport by week 8. Polymers (Pluronic® 127, carboxymethyl cellulose, and chitosan) demonstrated no significant cellular toxicity to human nasal epithelial cells up to 4 mg/mL and up to 1 mM for AMT (IC50: 4.5 ± 0.05 mM). Optimized formulation carboxymethyl cellulose and optimal formulation chitosan demonstrated slower release across an in vitro human nasal airway model (43%-44% vs 79 ± 4.58% for AMT). Using a human nasal cast model, deposition into the olfactory regions (potential nose-to-brain) was demonstrated on nozzle insertion (5 mm), whereas tilting of the head forward (15°) resulted in greater deposition in the bulk of the nasal cavity. PMID:26886345

  19. Intranasal immunization against dental caries with a Streptococcus mutans-enriched fimbrial preparation.

    Science.gov (United States)

    Fontana, M; Dunipace, A J; Stookey, G K; Gregory, R L

    1999-05-01

    Streptococcus mutans has been identified as the major etiological agent of human dental caries. The first step in the initiation of infection by this pathogenic bacterium is its attachment (i.e., through bacterial surface proteins such as glucosyltransferases, P1, glucan-binding proteins, and fimbriae) to a suitable receptor. It is hypothesized that a mucosal vaccine against a combination of S. mutans surface proteins would protect against dental caries by inducing specific salivary immunoglobulin A (IgA) antibodies which may reduce bacterial pathogenesis and adhesion to the tooth surface by affecting several adhesins simultaneously. Conventional Sprague-Dawley rats, infected with S. mutans at 18 to 20 days of age, were intranasally immunized with a mixture of S. mutans surface proteins, enriched for fimbriae and conjugated with cholera toxin B subunit (CTB) plus free cholera toxin (CT) at 13, 15, 22, 29, and 36 days of age (group A). Control rats were either not immunized (group B) or immunized with adjuvant alone (CTB and CT [group C]). At the termination of the study (when rats were 46 days of age), immunized animals (group A) had significantly (P dental caries.

  20. Intranasal immunization with nontypeable Haemophilus influenzae outer membrane vesicles induces cross-protective immunity in mice.

    Directory of Open Access Journals (Sweden)

    Sandro Roier

    Full Text Available Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act as a commensal and a pathogen of the respiratory tract. Especially nontypeable H. influenzae (NTHi is a major threat to public health and is responsible for several infectious diseases in humans, such as pneumonia, sinusitis, and otitis media. Additionally, NTHi strains are highly associated with exacerbations in patients suffering from chronic obstructive pulmonary disease. Currently, there is no licensed vaccine against NTHi commercially available. Thus, this study investigated the utilization of outer membrane vesicles (OMVs as a potential vaccine candidate against NTHi infections. We analyzed the immunogenic and protective properties of OMVs derived from various NTHi strains by means of nasopharyngeal immunization and colonization studies with BALB/c mice. The results presented herein demonstrate that an intranasal immunization with NTHi OMVs results in a robust and complex humoral and mucosal immune response. Immunoprecipitation revealed the most important immunogenic proteins, such as the heme utilization protein, protective surface antigen D15, heme binding protein A, and the outer membrane proteins P1, P2, P5 and P6. The induced immune response conferred not only protection against colonization with a homologous NTHi strain, which served as an OMV donor for the immunization mixtures, but also against a heterologous NTHi strain, whose OMVs were not part of the immunization mixtures. These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections.

  1. Comparison of traditional intranasal and aerosol inhalation inoculation of mice with influenza A viruses.

    Science.gov (United States)

    Belser, Jessica A; Gustin, Kortney M; Katz, Jacqueline M; Maines, Taronna R; Tumpey, Terrence M

    2015-07-01

    Intranasal instillation of virus in a liquid suspension (IN) is the most frequently employed method to inoculate small mammalian models with influenza virus, but does not reflect a natural route of exposure. In contrast, inoculation via aerosol inhalation (AR) more closely resembles human exposure to influenza virus. Studies in mice have yielded conflicting results regarding virulence induced by virus inoculated by these routes, and have not controlled for potential strain-specific differences, or examined contemporary influenza viruses and avian viruses with pandemic potential. We used a whole-body AR inoculation method to compare infectivity and disease progression of a highly pathogenic H5N1, a low pathogenic H7N9, and a 2009 H1N1 virus with traditional IN inoculation in the mouse model. Generally comparable levels of morbidity and mortality were observed with all viruses examined using either inoculation route, indicating that both IN and AR delivery are appropriate for murine studies investigating influenza virus pathogenicity. PMID:25771498

  2. Administrative Reform

    OpenAIRE

    Beh, LooSee

    2007-01-01

    This paper seeks to develop an understanding of the issues that public administrators should strive to provide in ethical practices and governance thus allowing distinctive administrative and social traditions that each country possess to flourish. Significant changes and continuities in the realm of government in contemporary China and Malaysia will be drawn upon. Recent developments have brought a sense of urgency in contrast to complacency with the status quo. This paper reviews pertinent ...

  3. Offentlig administration

    DEFF Research Database (Denmark)

    Nielsen, Elof Nellemann; Rehr, Preben René

    En undervisningsbog der henvender sig til administrationsbacheloruddannelsen. Kapitlerne er inddelt efter modulerne på uddannelsen og indeholder derfor elementer af administration, forvaltning, økonomistyring, innovation, samfundsvidenskabelige metoder og politisk styrede organisationer.......En undervisningsbog der henvender sig til administrationsbacheloruddannelsen. Kapitlerne er inddelt efter modulerne på uddannelsen og indeholder derfor elementer af administration, forvaltning, økonomistyring, innovation, samfundsvidenskabelige metoder og politisk styrede organisationer....

  4. SAT administrator

    International Nuclear Information System (INIS)

    SAT Administrator is the Information System for Nuclear Power Plant Personnel Training Program Design. It supports the design of training programs in the following phases: job analysis; task analysis; competency analysis; task competency association; definition of learning objectives to competencies; training program design; definition of test items. The general structure of the database and management software supports application of the SAT Administrator in any nuclear power installation

  5. Effects of Oxytocin Administration on the Response of Piglets to Weaning

    Science.gov (United States)

    Rault, Jean-Loup; Dunshea, Frank R.; Pluske, John R.

    2015-01-01

    Simple Summary Weaning is a stressful milestone for domestic animals. It is often performed at an early age and as an abrupt change in comparison to the transitional period seen in feral or wild animals. Oxytocin, a hormone associated with attachment, could improve the response of piglets to weaning. Piglets were either given oxytocin intranasally, subcutaneously, or handled as controls. Oxytocin had no effect on the physiological response to weaning. However, oxytocin increased the frequency of mild aggressive social behaviors between OT-administered and control pigs. Hence, the use of a single administration of oxytocin prior to weaning in pigs is not recommended. Abstract Weaning is often an abrupt and stressful process. We studied the effects of administering oxytocin, subcutaneously or intranasally, on the ability of pigs to cope with weaning. On a commercial farm 144, 30 day-old pigs from 24 litters were used. On the day of weaning, one male and one female in each litter were administered one of three treatments: intranasal oxytocin (24 International Unit), subcutaneous oxytocin (10 International Unit per kg of body weight), or handled as a control. The pigs were placed in one of eight weaner pens, split by sex and with an equal representation of treatments. Data included body weight and growth, physiology (neutrophil:lymphocyte ratio, plasma cortisol, C-reactive protein and Tumor Necrosis Factor-α concentrations), and behavior (feeding, drinking, social behavior). Both oxytocin treatments tended to result in higher levels of mild aggression within groups (p = 0.08), specifically between oxytocin-administered and control pigs (subcutaneous to control p = 0.03; intranasal to control p = 0.10). Subcutaneously-administered pigs tended to frequent the feeder more often than intranasally-administered pigs (p < 0.10), with the latter having slightly lower body weight 38 days post-weaning (p = 0.03). However, acute oxytocin administration did not result in any

  6. Administrative Reform

    DEFF Research Database (Denmark)

    Plum, Maja

    Through the example of a Danish reform of educational plans in early childhood education, the paper critically addresses administrative educational reforms promoting accountability, visibility and documentation. Drawing on Foucaultian perspectives, the relation between knowledge and governing...... of administrative technology, tracing how the humanistic values of education embed and are embedded within ‘the professional nursery teacher' as an object and subject of administrative practice. Rather than undermining the humanistic potential of education, it is argued that the technology of accounting......, implied in the reform, is analysed as a technology of accounting. A technology producing ‘the professional nursery teacher' as a reflective daily researcher, who outlives her pedagogical desire as an analytical care of the optimisation of ‘the learning child'. Thus, the paper analyses the micro physics...

  7. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice.

    Directory of Open Access Journals (Sweden)

    Shana P C Barroso

    Full Text Available Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling. Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus.

  8. Database Administrator

    Science.gov (United States)

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  9. Administrative IT

    Science.gov (United States)

    Grayson, Katherine, Ed.

    2006-01-01

    When it comes to Administrative IT solutions and processes, best practices range across the spectrum. Enterprise resource planning (ERP), student information systems (SIS), and tech support are prominent and continuing areas of focus. But widespread change can also be accomplished via the implementation of campuswide document imaging and sharing,…

  10. Preclinical evaluation of a replication-deficient intranasal DeltaNS1 H5N1 influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Julia Romanova

    Full Text Available BACKGROUND: We developed a novel intranasal influenza vaccine approach that is based on the construction of replication-deficient vaccine viruses that lack the entire NS1 gene (DeltaNS1 virus. We previously showed that these viruses undergo abortive replication in the respiratory tract of animals. The local release of type I interferons and other cytokines and chemokines in the upper respiratory tract may have a "self-adjuvant effect", in turn increasing vaccine immunogenicity. As a result, DeltaNS1 viruses elicit strong B- and T- cell mediated immune responses. METHODOLOGY/PRINCIPAL FINDINGS: We applied this technology to the development of a pandemic H5N1 vaccine candidate. The vaccine virus was constructed by reverse genetics in Vero cells, as a 5:3 reassortant, encoding four proteins HA, NA, M1, and M2 of the A/Vietnam/1203/04 virus while the remaining genes were derived from IVR-116. The HA cleavage site was modified in a trypsin dependent manner, serving as the second attenuation factor in addition to the deleted NS1 gene. The vaccine candidate was able to grow in the Vero cells that were cultivated in a serum free medium to titers exceeding 8 log(10 TCID(50/ml. The vaccine virus was replication deficient in interferon competent cells and did not lead to viral shedding in the vaccinated animals. The studies performed in three animal models confirmed the safety and immunogenicity of the vaccine. Intranasal immunization protected ferrets and mice from being infected with influenza H5 viruses of different clades. In a primate model (Macaca mulatta, one dose of vaccine delivered intranasally was sufficient for the induction of antibodies against homologous A/Vietnam/1203/04 and heterologous A/Indonesia/5/05 H5N1 strains. CONCLUSION/SIGNIFICANCE: Our findings show that intranasal immunization with the replication deficient H5N1 DeltaNS1 vaccine candidate is sufficient to induce a protective immune response against H5N1 viruses. This approach

  11. Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang Bing; Feng Weiyue, E-mail: fengwy@mail.ihep.ac.cn; Zhu Motao; Wang Yun; Wang Meng [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Gu Yiqun [Maternity Hospital of Haidian District (China); Ouyang Hong; Wang Huajian; Li Ming; Zhao Yuliang, E-mail: zhaoyuliang@mail.ihep.ac.cn; Chai Zhifang [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Wang Haifang [Peking University, College of Chemistry and Molecular Engineering (China)

    2009-01-15

    Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe{sub 2}O{sub 3} nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 {mu}g) intranasal exposure of nano- and submicron-sized Fe{sub 2}O{sub 3} particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe{sub 2}O{sub 3} particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe{sub 2}O{sub 3} particle treatment (p < 0.05). The nano-sized Fe{sub 2}O{sub 3} generally induced greater alteration and more significant dose-effect response than the submicron-sized particle did. Some slight perturbation of monoamine neurotransmitters were found in the hippocampus after exposure to the two sizes of Fe{sub 2}O{sub 3} particle. The TEM image showed that some ultrastructural alterations in nerve cells, including neurodendron degeneration, membranous structure disruption and lysosome increase in the olfactory bulb, slight dilation in the rough endoplasmic reticulum and lysosome increase in the hippocampus were induced by the nano-sized Fe{sub 2}O{sub 3} treatment. In contrast, in the submicron-sized Fe{sub 2}O{sub 3} treated mice, slightly swollen mitochondria and some vacuoles were observed in the olfactory bulb and hippocampus, respectively. These results indicate that intranasal exposure of Fe{sub 2}O{sub 3} nanoparticles could induce more severe oxidative stress and nerve cell damage in the brain than the

  12. Adjuvant requirement for successful immunization with recombinant derivatives of Plasmodium vivax merozoite surface protein-1 delivered via the intranasal route

    Directory of Open Access Journals (Sweden)

    Daniel Y Bargieri

    2007-06-01

    Full Text Available Recently, we generated two bacterial recombinant proteins expressing 89 amino acids of the C-terminal domain of the Plasmodium vivax merozoite surface protein-1 and the hexa-histidine tag (His6MSP1(19. One of these recombinant proteins contained also the amino acid sequence of the universal pan allelic T-cell epitope (His6MSP1(19-PADRE. In the present study, we evaluated the immunogenic properties of these antigens when administered via the intra-nasal route in the presence of distinct adjuvant formulations. We found that C57BL/6 mice immunized with either recombinant proteins in the presence of the adjuvants cholera toxin (CT or the Escherichia coli heat labile toxin (LT developed high and long lasting titers of specific serum antibodies. The induced immune responses reached maximum levels after three immunizing doses with a prevailing IgG1 subclass response. In contrast, mice immunized by intranasal route with His6MSP1(19-PADRE in the presence of the synthetic oligonucleotides adjuvant CpG ODN 1826 developed lower antibody titers but when combined to CT, CpG addition resulted in enhanced IgG responses characterized by lower IgG1 levels. Considering the limitations of antigens formulations that can be used in humans, mucosal adjuvants can be a reliable alternative for the development of new strategies of immunization using recombinant proteins of P. vivax.

  13. Pain modulation by intranasal oxytocin and emotional picture viewing — a randomized double-blind fMRI study

    Science.gov (United States)

    Zunhammer, Matthias; Geis, Sandra; Busch, Volker; Eichhammer, Peter; Greenlee, Mark W.

    2016-01-01

    The hormone oxytocin has been hypothesized to influence the emotional dimension of pain. This randomized, placebo-controlled, double-blind, crossover study explored whether intranasal oxytocin and emotional context can affect heat pain perception in 30 healthy male volunteers. After receiving 36 IU oxytocin or placebo, participants underwent functional Magnetic Resonance Imaging (fMRI) during which noxious and non-noxious thermode heat stimuli were applied. Simultaneously, scenes from the International Affective Pictures System (IAPS) with positive, neutral, and negative emotional valence were shown. Heat intensity and unpleasantness ratings were obtained. The activity of whole-brain correlates of heat processing was quantified via multi-voxel pattern analysis. We observed no appreciable main effects of oxytocin on ratings or neural pain correlates. Effects of emotional picture valence on ratings were smaller than reported in previous studies. Nevertheless, oxytocin was found to significantly enhance the influence of picture valence on unpleasantness ratings at noxious heat levels. No corresponding changes in whole-brain correlates of heat intensity processing were found. Our study provides evidence that intranasal oxytocin increases the effects of emotional context on the subjective unpleasantness of experimental heat pain. Future studies are needed to determine whether this effect can be utilized in clinical settings. PMID:27546446

  14. Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study.

    Science.gov (United States)

    Zunhammer, Matthias; Geis, Sandra; Busch, Volker; Eichhammer, Peter; Greenlee, Mark W

    2016-01-01

    The hormone oxytocin has been hypothesized to influence the emotional dimension of pain. This randomized, placebo-controlled, double-blind, crossover study explored whether intranasal oxytocin and emotional context can affect heat pain perception in 30 healthy male volunteers. After receiving 36 IU oxytocin or placebo, participants underwent functional Magnetic Resonance Imaging (fMRI) during which noxious and non-noxious thermode heat stimuli were applied. Simultaneously, scenes from the International Affective Pictures System (IAPS) with positive, neutral, and negative emotional valence were shown. Heat intensity and unpleasantness ratings were obtained. The activity of whole-brain correlates of heat processing was quantified via multi-voxel pattern analysis. We observed no appreciable main effects of oxytocin on ratings or neural pain correlates. Effects of emotional picture valence on ratings were smaller than reported in previous studies. Nevertheless, oxytocin was found to significantly enhance the influence of picture valence on unpleasantness ratings at noxious heat levels. No corresponding changes in whole-brain correlates of heat intensity processing were found. Our study provides evidence that intranasal oxytocin increases the effects of emotional context on the subjective unpleasantness of experimental heat pain. Future studies are needed to determine whether this effect can be utilized in clinical settings. PMID:27546446

  15. Intramuscular priming and intranasal boosting induce strong genital immunity through secretory IgA in minipigs infected with Chlamydia trachomatis

    Directory of Open Access Journals (Sweden)

    Emma eLorenzen

    2015-12-01

    Full Text Available International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. Intramuscular priming immunizations with CAF01 induced a significant cell-mediated IFN-ɣ and IL-17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC, we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggest that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general.

  16. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    Science.gov (United States)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah; Erneholm, Karin; Olsen, Anja Weinreich; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter

    2015-01-01

    International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general. PMID:26734002

  17. Intranasal "painless" human Nerve Growth Factor [corrected] slows amyloid neurodegeneration and prevents memory deficits in App X PS1 mice.

    Directory of Open Access Journals (Sweden)

    Simona Capsoni

    Full Text Available Nerve Growth Factor (NGF is being considered as a therapeutic candidate for Alzheimer's disease (AD treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V, which would allow increasing the dose of NGF without triggering pain. We show that "painless" hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8, hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of "painless" hNGF variants as a new generation of therapeutics for neurodegenerative diseases.

  18. Administrative decisions

    International Nuclear Information System (INIS)

    This article reviews relevant administrative decisions that have been taken in various countries during the last semester of 1999 and the first one of 2000. In Argentina, an inter-ministerial commission has been settled to examine the prospects of completing the construction of the Atucha-2 unit. In Sweden, an agreement has been signed between Sydkraft, Vattenfall and the Swedish government on a compensation plan for the early shutdown of the Barsebaeck unit 1. In Switzerland, the government of the canton of Bern has rejected a constitutional initiative requesting the shutdown of the Muehleberg nuclear power plant. (A.C.)

  19. 右美托咪定滴鼻对小儿七氟烷麻醉术前焦虑和术后躁动的影响%Effects of intranasal dexmedetomidine as premedication on preoperative anxiety and emergence delirium after sevoflurane anesthesia in children

    Institute of Scientific and Technical Information of China (English)

    高燕春; 谢言虎; 柴小青; 侯冠峰; 方才

    2012-01-01

    目的 观察右美托咪定(DM)滴鼻对小儿术前焦虑和术后躁动的影响.方法 将60例1-4岁疝气手术小儿随机均分为三组.七氟烷麻醉诱导前30 min,Ⅱ、Ⅲ组分别予以DM 0.5μg/kg和1μg/g滴鼻,Ⅰ组滴生理盐水0.4ml对照.连续监测BP、HR、SpO2、PET CO2.观察患儿入室的镇静情绪评分、诱导时间、麻醉时间、苏醒时间、不良反应及术后患儿的躁动评分.结果 Ⅲ组患儿术前镇静满意率明显高于Ⅰ组和Ⅱ组(45% vs.10%和15%)(P<0.05).与Ⅰ组、Ⅱ组比较,Ⅲ组躁动评分和诱导时间明显降低(P<0.01).三组间苏醒时间差异无统计学意义(P>0.05).结论 诱导前应用DM 1 μg/kg滴鼻可有效改善小儿术前焦虑情绪,缩短七氟烷麻醉诱导时间,降低苏醒期躁动的发生率,且不延长苏醒时间.%Objective To observe the effects of intranasal dexmedetomidine ( DM ) as premedication on preoperative anxiety and emergence delirium after sevoflurane anesthesia in children. Methods Sixty of 1-4 year-old children undergoing hernia surgery under sevoflurane anesthesia were equally randomized into tree groups of A(intranasal DM 0. 5 fig/kg) .B( intranasal DM 1 μg/kg) and C (intranasal normal saline 0. 4 ml). Sevoflurane anesthesia was induced at 30 minutes after intranasal administration. BP, HR and Sp()z were monitored during the operation. The sadation scores, the times for induction,anesthesia and awaken, adverse reactions, agitation scores were recorded. Results The satisfaction rate for preanesthesia sedation was significantly higher in group B than that in groups of A and C(45% vs. \\0% and 15%)(P0. 05). Conclusion Intranasal DM 1 fig/kg as premedication is effective for reducing anxiety and the incidence of emergence delirium without delaying the awakening time.

  20. ADMINISTRATIVE CIRCULARS

    CERN Multimedia

    Division des ressources humaines

    2000-01-01

    N° 2 (Rev. 1) - March 2000Guidelines and procedures concerning recruitment and probation period of staff membersN° 9 (Rev. 2) - March 2000Staff members contractsN° 16 (Rev. 2) - January 2000TrainingN° 30 (Rev. 1) - January 2000Indemnities and reimbursements upon taking up appointment and termination of contractN° 32 - February 2000Principles and procedures governing complaints of harassmentThese circular have been amended (No 2, N° 9, N° 16 and N° 30) or drawn up (N° 32).Copies are available in the Divisional Secretariats.Note:\tAdministrative and operational circulars, as well as the lists of those in force, are available for consultation in the server SRV4_Home in the Appletalk zone NOVELL (as GUEST or using your Novell username and password), volume PE Division Data Disk.The Word files are available in the folder COM, folder Public, folder ADM.CIRC.docHuman Resources DivisionTel. 74128

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

    Directory of Open Access Journals (Sweden)

    Lakshmi Jayaraman

    2013-01-01

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

  2. Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8⁺ T Lymphocytes in the Female Reproductive Tract.

    Science.gov (United States)

    Singh, Shailbala; Schluns, Kimberly S; Yang, Guojun; Anthony, Scott M; Barry, Michael A; Sastry, K Jagannadha

    2016-03-17

    Immunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT) can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV) and human papillomaviruses (HPV). The kinetics and mechanisms of regulation of vaccine-induced adaptive T cell-mediated immune responses in FRT are less well defined. We present here evidence for intranasal delivery of the model antigen ovalbumin (OVA) along with alpha-galactosylceramide adjuvant as a protein vaccine to induce significantly higher levels of antigen-specific effector and memory CD8⁺ T cells in the FRT, relative to other systemic and mucosal tissues. Antibody blocking of the CXCR3 receptor significantly reduced antigen-specific CD8⁺ T cells subsequent to intranasal delivery of the protein vaccine suggesting an important role for the CXCR3 chemokine-receptor signaling for T cell trafficking. Further, intranasal vaccination with an adenoviral vector expressing OVA or HIV-1 envelope was as effective as intramuscular vaccination for generating OVA- or ENV-specific immunity in the FRT. These results support the application of the needle-free intranasal route as a practical approach to delivering protein as well as DNA/virus vector-based vaccines for efficient induction of effector and memory T cell immunity in the FRT.

  3. Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in 3-week-old calves experimentally challenged with BRSV

    NARCIS (Netherlands)

    Vangeel, I.; Antonis, A.F.G.; Fluess, M.; Peters, A.R.; Harmeyer, S.S.

    2007-01-01

    Two experimental bovine respiratory syncytial virus (BRSV) challenge studies were undertaken to evaluate the efficacy of a single intranasal dose of a bivalent modified live vaccine containing BRSV in 3-week-old calves. In the first study, vaccine efficacy was evaluated in colostrum deprived (matern

  4. Sedative and Analgesic Effects of Intranasal Dexmedetomidine in Mandibular Third Molar Extraction%鼻腔喷雾右美托咪定在下颌第三磨牙拔除术中的应用

    Institute of Scientific and Technical Information of China (English)

    顾春梅; 仲元萍; 黄兰柱; 史艳红

    2014-01-01

    目的:探讨鼻腔喷雾右美托咪定在下颌第三磨牙拔除术中的临床应用价值。方法:30例需拔除下颌第三磨牙的患者随机分为右美托咪定组(DEX组)和对照组(C组),每组15例。DEX组鼻腔喷雾1.5μg/kg右美托咪定,C组鼻腔喷雾生理盐水,30 min 以后实施局部麻醉,拔出下颌第三磨牙。每10 min 记录患者的收缩压(SBP)、心率(HR)、血氧饱和度(SpO2),评估患者的改良OAA/S评分,同时记录注射局麻药时的VAS评分。结果:DEX组的SBP和HR在鼻腔喷雾给药后的30~60 min出现一定程度下降,与C组比较,差异有统计学意义(P0.05)。结论:鼻腔喷雾右美托咪定1.5μg/kg,能够有效、安全且便捷地应用于健康成人下颌第三磨牙拔除术中的镇静,缓解患者的焦虑情绪。%Objective: To evaluate the effect of atomized dexmedetomidine for sedation in patients undergoing mandibular third molar removal. Methods: Thirty patients underwent mandibular third molar removal were randomly assigned into 2 groups:group DEX, nasal spray with 1.5 μg/kg atomized dexmedetomidine;group C, nasal spray with normal saline. Local anaesthesia was injected 30 min after nasal spray. During the process of extraction, SBP, HR and SpO 2 were recorded at every 10 min period. Sedation status was measured at every 10 min with a modified Observer's Assessment of Alertness/Sedation (OAA/S) scale. Pain from local anaesthesia infiltration was rated on a scale from 0 to 10. Results: Group DEX patients displayed decreased SBP and HR at 30-60 min after intranasal dexmedetomidine, which were significantly different from group C(P<0.05). Sedation values in group DEX were significantly different from group C at 20-60 min after intranasal drug administration (P<0.05). No significant differences were observed between the groups in terms of the pain score during LA injection. Conclusion: Intranasal administration of 1.5 μg/kg atomized

  5. Comparison of pathogenicities of H7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques.

    Science.gov (United States)

    Shichinohe, Shintaro; Itoh, Yasushi; Nakayama, Misako; Ozaki, Hiroichi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-06-01

    The outbreak of H7N9 low pathogenic avian influenza viruses in China has attracted attention to H7 influenza virus infection in humans. Since we have shown that the pathogenicity of H1N1 and H5N1 influenza viruses in macaques was almost the same as that in humans, we compared the pathogenicities of H7 avian influenza viruses in cynomolgus macaques via intranasal and conjunctival inoculation, which mimics natural infection in humans. H7N9 virus, as well as H7N7 highly pathogenic avian influenza virus, showed more efficient replication and higher pathogenicity in macaques than did H7N1 and H7N3 highly pathogenic avian influenza viruses. These results are different from pathogenicity in chickens as reported previously. Therefore, our results obtained in macaques help to estimate the pathogenicity of H7 avian influenza viruses in humans. PMID:26994587

  6. Heterosubtypic antiviral activity of hemagglutinin-specific antibodies induced by intranasal immunization with inactivated influenza viruses in mice.

    Directory of Open Access Journals (Sweden)

    Mieko Muramatsu

    Full Text Available Influenza A virus subtypes are classified on the basis of the antigenicity of their envelope glycoproteins, hemagglutinin (HA; H1-H17 and neuraminidase. Since HA-specific neutralizing antibodies are predominantly specific for a single HA subtype, the contribution of antibodies to the heterosubtypic immunity is not fully understood. In this study, mice were immunized intranasally or subcutaneously with viruses having the H1, H3, H5, H7, H9, or H13 HA subtype, and cross-reactivities of induced IgG and IgA antibodies to recombinant HAs of the H1-H16 subtypes were analyzed. We found that both subcutaneous and intranasal immunizations induced antibody responses to multiple HAs of different subtypes, whereas IgA was not detected remarkably in mice immunized subcutaneously. Using serum, nasal wash, and trachea-lung wash samples of H9 virus-immunized mice, neutralizing activities of cross-reactive antibodies were then evaluated by plaque-reduction assays. As expected, no heterosubtypic neutralizing activity was detected by a standard neutralization test in which viruses were mixed with antibodies prior to inoculation into cultured cells. Interestingly, however, a remarkable reduction of plaque formation and extracellular release of the H12 virus, which was bound by the H9-induced cross-reactive antibodies, was observed when infected cells were subsequently cultured with the samples containing HA-specific cross-reactive IgA. This heterosubtypic plaque reduction was interfered when the samples were pretreated with anti-mouse IgA polyclonal serum. These results suggest that the majority of HA-specific cross-reactive IgG and IgA antibodies produced by immunization do not block cellular entry of viruses, but cross-reactive IgA may have the potential to inhibit viral egress from infected cells and thus to play a role in heterosubtypic immunity against influenza A viruses.

  7. Construction and preliminary immunobiological characterization of a novel, non-reverting, intranasal live attenuated whooping cough vaccine candidate.

    Science.gov (United States)

    Cornford-Nairns, Renee; Daggard, Grant; Mukkur, Trilochan

    2012-06-01

    We describe the construction and immunobiological properties of a novel whooping cough vaccine candidate, in which the aroQ gene, encoding 3-dehydroquinase, was deleted by insertional inactivation using the kanamycin resistance gene cassette and allelic exchange using a Bordetella suicide vector. The aroQ B. pertussis mutant required supplementation of media to grow but failed to grow on an unsupplemented medium. The aroQ B. pertussis mutant was undetectable in the trachea and lungs of mice at days 6 and 12 post-infection, respectively. Antigen-specific antibody isotypes IgG1 and IgG2a, were produced, and cell-mediated immunity [CMI], using interleukin-2 and interferon-gamma as indirect indicators, was induced in mice vaccinated with the aroQ B. pertussis vaccine candidate, which were substantially enhanced upon second exposure to virulent B. pertussis. Interleukin- 12 was also produced in the aroQ B. pertussis-vaccinated mice. On the other hand, neither IgG2a nor CMI-indicator cytokines were produced in DTaP-vaccinated mice, although the CMI-indicator cytokines became detectable post-challenge with virulent B. pertussis. Intranasal immunization with one dose of the aroQ B. pertussis mutant protected vaccinated mice against an intranasal challenge infection, with no pathogen being detected in the lungs of immunized mice by day 7 post-challenge. B. pertussis aroQ thus constitutes a safe, non-reverting, metabolite-deficient vaccine candidate that induces both humoral and cellmediated immune responses with potential for use as a single-dose vaccine in adolescents and adults, in the first instance, with a view to disrupting the transmission cycle of whooping cough to infants and the community.

  8. ROLE OF HOSPITAL ADMINISTRATION

    OpenAIRE

    UDAYSINH R. MANEPATIL

    2013-01-01

    Hospital administration is the management of the hospital as a business. The administration is made up of medical and health services managers (sometimes called health care executives and health care administrators) and assistant administrators. Administrations range in size and the duties of the administrator depends on the size of the administration.

  9. EFEITOS ANESTÉSICOS DA ADMINISTRAÇÃO INTRANASAL OU INTRAMUSCULAR DA ASSOCIAÇÃO DE MIDAZOLAM E CETAMINA RACÊMICA OU S+ EM PERIQUITO AUSTRALIANO (Melopsittacus undulatus)

    OpenAIRE

    Gustavo Aléssio Trevisan; Everton Leonardi da Silva; Anderson Luiz de Carvalho; Rafael Messias Luiz

    2016-01-01

    Intranasal anesthesia in birds is considered a safe, simple and efficient technique. The aim of this study was compare the anesthetic effects of midazolam (5 mg.kg-1) with racemic (R) or S+ (S) ketamine (15 mg.kg-1), administered intranasally (IN) or intramuscularly (IM) in budgerigars (Melopsittacus undulatus). Eight budgerigars were used in a crossover design with four treatments: INR, INS, IMR and IMS. Onset time, dorsal recumbency time duration, total anesthesia time, total recovery time,...

  10. Administrative Appeals and ADR in Danish Administrative Law

    DEFF Research Database (Denmark)

    Conradsen, Inger Marie; Gøtze, Michael

    2014-01-01

    Administrative Appeals, review, administrative tribunals, ombudsman, alternative dispute resolution......Administrative Appeals, review, administrative tribunals, ombudsman, alternative dispute resolution...

  11. Intranasal Delivery of Cationic PLGA Nano/Microparticles- Loaded FMDV DNA Vaccine Encoding IL-6 Elicited Protective Immunity against FMDV Challenge

    OpenAIRE

    Gang Wang; Li Pan; Yongguang Zhang; Yonglu Wang; Zhongwang Zhang; Jianliang Lü; Peng Zhou; Yuzhen Fang; Shoutian Jiang

    2011-01-01

    Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV) and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide)) nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing m...

  12. Chimeric flagellin expressed by Salmonella typhimurium induces an ESAT-6-specific Th 1-type immune response and CTL effects following intranasal immunization

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Liu Liu; Ke Wen; Jinlin Huang; Shizhong Geng; Junsong Shen; Zhiming Pan; Xinan Jiao

    2011-01-01

    The flagellin component FliC of Salmonella typhimurium is capable of activating the innate immune system via specific interactions with TLR5 and can also act as a carrier of foreign antigen to elicit antigen-specific immune responses.Thus,we constructed an attenuated Salmonella strain SL5928(fliC/esat) expressing chimeric flagellin that contained the ESAT-6 antigen coding sequence of Mycobacterium tuberculosis inserted into the highly variable region of the Salmonella flagellin coding gene fliCi.The chimeric flagellin functioned normally,as demonstrated using a flagella swarming assay and electron microscopy.To analyze the effects of chimeric flagellin,the cell-mediated immune response and cytotoxic T lymphocyte (CTL) effects specific for ESAT-6antigen were tested after intranasal immunization of mice with flagellated Salmonella SL5928(fliC/esat).The results showed that SL5928(fliC/esat) intranasal immunization can strongly elicit an ESAT-6-specific T helper (Th) 1-type immune response in mucosal lymphoid tissues,such as nasopharynx-associated lymph nodes,lung and Peyer's patches,and a Th 1/Th2 response was elicited in spleen and mesenteric lymph nodes.Furthermore,intranasal immunization of SL5928(fliC/esat) produced efficient CTL effects,as demonstrated using a 5-and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) assay.Thus,our study revealed that Salmonella flagellin acts as a carrier for foreign antigen and triggers strong Th 1 and CTL responses during intranasal immunization.Chimeric flagellin is potentially an effective strategy for the development of novel vaccines against tuberculosis in humans and animals.

  13. Intranasal application of immuno-regulatory molecules: a method to investigate strategies for local cancer immuno-therapies in the lung

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Sarah Reppert, Katerina Andreev, Sandra Wittmann & Susetta Finotto ### Abstract Lung cancer is one of the most frequently occurring cancer types. Successful lung cancer therapies in patients require preliminary investigations of promising therapeutic reagents in animal models. This protocol describes a method to induce lung tumours in mice and to deliver an immunoregulatory molecule directly to the lung by intranasal application. Here we describe the usage of murine ce...

  14. Intranasal Delivery of Cell-Penetrating anti-NF-κB Peptides (Tat-NBD) Alleviates Infection-Sensitized Hypoxic-Ischemic Brain Injury

    OpenAIRE

    Yang, Dianer; Sun, Yu-Yo; Lin, Xiaoyi; Baumann, Jessica M.; Dunn, R. Scott; Lindquist, Diana M.; Kuan, Chia-Yi

    2013-01-01

    Perinatal infection aggravates neonatal hypoxic-ischemic (HI) brain injury and may interfere with therapeutic hypothermia. While the NF-κB signaling pathway has been implicated in microglia activation in infection-sensitized HI, the current therapeutic strategies rely on systemic intervention, which could impair neonatal immunity and increase the risk of severe infection. To devise a brain-targeted anti-NF-κB strategy, we examined the effects of intranasal delivery of tat-NBD peptides in two ...

  15. Effect of Intranasal or Aerosol Challenge on Airway Inflammation in a Murine Asthma Model%滴鼻和雾化两种不同激发方式对小鼠支气管哮喘模型气道炎症的影响

    Institute of Scientific and Technical Information of China (English)

    程胜; 陈辉龙; 王正云; 王爱利; 谢敏; 曹勇; 谢俊刚; 熊维宁; 徐永健

    2014-01-01

    .The concentrations of IL-4 and IL-13 in the supernatant of BALF were determined by ELISA and the histological changes in the lung by hematoxylin and eosin (HE) staining.Results The total leukocytes were highest in the intranasal group.The number of eosinophils and neutrophils in the intranasal group were higher than that in the aerosol group and normal group (P< 0.05).The levels of IL-4 and IL-13 were significantly increased in the supernatant of BALF in the intranasal group when compared with the aerosol group and normal group (P<0.05).The levels of IL-4 and IL-13 in the aerosol group were higher than those in the normal group (P<0.05).The lung tissue inflammation presented destruction of epithelial cells ,hyperplasia of goblet cells and infiltration of large numbers of inflammatory cells (predominantly eosinophils and lymphocytes ).It was most obvious in the intranasal group and no obvious inflammation was observed in the normal group.Conclusion Asthmatic models can be established successfully by both of intranasal and aerosol challenge and the in-tranasal administration triggers more serious airway inflammation and higher cytokines expression than aerosol challenge ,provi-ding better choice for the study of asthma.

  16. Levofloxacin rescues mice from lethal intra-nasal infections with virulent Francisella tularensis and induces immunity and production of protective antibody.

    Science.gov (United States)

    Klimpel, Gary R; Eaves-Pyles, Tonyia; Moen, Scott T; Taormina, Joanna; Peterson, Johnny W; Chopra, Ashok K; Niesel, David W; Carness, Paige; Haithcoat, Judith L; Kirtley, Michelle; Nasr, Abdelhakim Ben

    2008-12-01

    The ability to protect mice against respiratory infections with virulent Francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. In this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with F. tularensis SCHU S4. We show that mice infected with a lethal dose of SCHU S4, via an intra-nasal challenge, could be protected with levofloxacin treatment. This protection was evident even when levofloxacin treatment was delayed 72h post-infection. At early time points after levofloxacin treatment, significant numbers of bacteria could be recovered from the lungs and spleens of mice, which was followed by a dramatic disappearance of bacteria from these tissues. Mice successfully treated with levofloxacin were later shown to be almost completely resistant to re-challenge with SCHU S4 by the intra-nasal route. Serum antibody appeared to play an important role in this immunity. Normal mice, when given sera from animals protected by levofloxacin treatment, were solidly protected from a lethal intra-nasal challenge with SCHU S4. The protective antiserum contained high titers of SCHU S4-specific IgG2a, indicating that a strong Th1 response was induced following levofloxacin treatment. Thus, this study describes a potentially valuable animal model for furthering our understanding of respiratory tularemia and provides suggestive evidence that antibody can protect against respiratory infections with virulent F. tularensis. PMID:18930100

  17. Senior Administrators Should Have Administrative Contracts.

    Science.gov (United States)

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  18. Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict

    Science.gov (United States)

    Nater, Urs M.; Schaer, Marcel; La Marca, Roberto; Bodenmann, Guy; Ehlert, Ulrike; Heinrichs, Markus

    2013-01-01

    Unhappy couple relationships are associated with impaired individual health, an effect thought to be mediated through ongoing couple conflicts. Little is known, however, about the underlying mechanisms regulating psychobiological stress, and particularly autonomic nervous system (ANS) reactivity, during negative couple interaction. In this study, we tested the effects of the neuropeptide oxytocin on ANS reactivity during couple conflict in a standardized laboratory paradigm. In a double-blind, placebo-controlled design, 47 heterosexual couples (total n = 94) received oxytocin or placebo intranasally prior to instructed couple conflict. Participants’ behavior was videotaped and salivary alpha-amylase (sAA), a measure of sympathetic activity, and emotional arousal were repeatedly measured during the experiment. Oxytocin significantly reduced sAA during couple conflict in women, whereas men showed increases in sAA levels (sex × group interaction: B = −49.36, t = −2.68, P = 0.009). In men, these increases were related to augmented emotional arousal (r = 0.286, P = 0.028) and more positive behavior (r = 0.291, P = 0.026), whereas there was no such association in women. Our results imply sex-specific effects of oxytocin on sympathetic activity, to negative couple interaction, with the neuropeptide reducing sAA responses and emotional arousal in women while increasing them in men. PMID:22842905

  19. Mucosal Antibodies Induced by Intranasal but Not Intramuscular Immunization Block Norovirus GII.4 Virus-Like Particle Receptor Binding.

    Science.gov (United States)

    Tamminen, Kirsi; Malm, Maria; Vesikari, Timo; Blazevic, Vesna

    2016-06-01

    Noroviruses (NoVs) account for the majority of diagnosed cases of viral acute gastroenteritis worldwide. Virus-like particle (VLP)-based vaccines against NoV are currently under development. Serum antibodies that block the binding of NoV VLPs to histo-blood group antigens, the putative receptors for NoV, correlate with protection against NoV infection. The role of functional mucosal antibodies in protection is largely unknown, even though the intestinal mucosa is the entry port for NoV. Balb/c mice were immunized intramuscularly (IM) or intranasally (IN) with NoV GII.4 VLPs, and systemic and mucosal blocking antibody responses were studied. IN immunization elicited NoV-specific serum and mucosal IgG and IgA antibodies, whereas IM immunized animals completely lacked IgA. Both immunization routes induced similar blocking activity in serum but only IN route generated blocking antibodies in mucosa. The level of IgA in the mucosal (nasal) lavages strongly correlated (r = 0.841) with the blocking activity, suggesting that IgA, but not IgG, is the major NoV blocking antibody on mucosal surfaces. The results indicate that only mucosal immunization route induces the development of functional anti-NoV IgA on mucosal surface. PMID:27135874

  20. Randomized, Double-Blind, and Placebo-Controlled Clinic Report of Intranasal Low-Intensity Laser Therapy on Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Timon Cheng-Yi Liu

    2012-01-01

    Full Text Available The intranasal low intensity GaInP/AlGaInP diode 650 nm laser therapy (ILGLT might improve blood lipid and hemorheologic behavior of patients in view of its previous research, but it should be further supported by a randomized, double-blind, and placebo-controlled clinical study. In this paper, 90 patients with coronary heart disease or cerebral infarction were randomly divided into two groups, 60 in the treatment group and 30 in the control group, and were blindly treated with ILGLT at 8.38 and 0 mW/cm2 for 30 min each time once a day ten days each session for two sessions between which there were three days for rest, respectively. Fasting blood lipid such as total cholesterol and low/high-density lipoprotein cholesterol and hemorheologic behavior such as blood viscosity, plasma viscosity, redox viscosity and red blood cell aggregation were assessed before the first treatment and after the two sessions and were found to be significantly improved by ILGLT. It was concluded that ILGLT may improve blood lipid and hemorheologic behavior of patients with coronary heart disease or cerebral infarction.

  1. Administrative Data Repository (ADR)

    Data.gov (United States)

    Department of Veterans Affairs — The Administrative Data Repository (ADR) was established to provide support for the administrative data elements relative to multiple categories of a person entity...

  2. EPA Administrative Enforcement Dockets

    Data.gov (United States)

    U.S. Environmental Protection Agency — The EPA Administrative Enforcement Dockets database contains the electronic dockets for administrative penalty cases filed by EPA Regions and Headquarters. Visitors...

  3. Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation.

    Science.gov (United States)

    Pallagi, Edina; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

    2015-08-01

    Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software(®)) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development.

  4. Organization/Administration.

    Science.gov (United States)

    Chaffee, Ellen Earle

    Patterns that emerged from reviewing 26 syllabi for courses on organization and administration in higher education are discussed, and six sample syllabi are presented. The syllabi focused more on organization than administration. Of the 26 syllabi, 19 dealt with organization and administration generally; 5 with administration in a specific…

  5. Formulation, high throughput in vitro screening and in vivo functional characterization of nanoemulsion-based intranasal vaccine adjuvants.

    Directory of Open Access Journals (Sweden)

    Pamela T Wong

    Full Text Available Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate formulations consisting of oil-in-water nanoemulsions that contain various cationic and nonionic surfactants. To facilitate adjuvant development we first evaluated this library in a series of high-throughput, in vitro assays for activities associated with innate and adaptive immune activation in vivo. These in vitro assays screened for the ability of the adjuvant to bind to mucin, induce cytotoxicity, facilitate antigen uptake in epithelial and dendritic cells, and activate cellular pathways. We then sought to determine how these parameters related to adjuvant activity in vivo. While the in vitro assays alone were not enough to predict the in vivo adjuvant activity completely, several interesting relationships were found with immune responses in mice. Furthermore, by varying the physicochemical properties of the surfactant components (charge, surfactant polar head size and hydrophobicity and the surfactant blend ratio of the formulations, the strength and type of the immune response generated (TH1, TH2, TH17 could be modulated. These findings suggest the possibility of using high-throughput screens to aid in the design of custom adjuvants with unique immunological profiles to match specific mucosal vaccine applications.

  6. Intranasal delivery of paroxetine nanoemulsion via the olfactory region for the management of depression: formulation, behavioural and biochemical estimation

    Science.gov (United States)

    Pandey, Yogendra Raj; Kumar, Shobhit; Gupta, Bijay Kumar; Ali, Javed; Baboota, Sanjula

    2016-01-01

    Paroxetine is a selective serotonin reuptake inhibitor (SSRI) and is used for the treatment of depression and anxiety problems, but suffers from the drawback of poor oral bioavailability (less than 50%) due to its extensive first pass metabolism. The objective of the present study was to develop a paroxetine loaded nanoemulsion (o/w type) for direct nose-to-brain delivery. Nanoemulsions were prepared by the spontaneous emulsification technique using Capmul MCM, Solutol HS 15 and propylene glycol as oil phase, surfactant and co-surfactant, respectively, for delivery of drug directly to the brain through the nasal route for better management of depression. Formulations were studied for droplet size, polydispersity index (PDI), percentage transmittance, refractive index, viscosity, zeta potential, surface morphology and in vitro permeation study. TEM images of optimized formulation showed spherical droplets with a mean diameter of 58.47 ± 3.02 nm, PDI of 0.339 ± 0.007 and zeta potential values of -33 mV. The formulation showed good results for transmittance (100.60 ± 0.577%), refractive index (1.412 ± 0.003) and viscosity (40.85 ± 6.40 cP). Permeation studies revealed a 2.57-fold enhancement in permeation as compared to the paroxetine suspension. Behavioural studies such as the forced swimming test and locomotor activity test were done on Wistar rats to study the antidepressant effect of the optimized formulation. Treatment of depressed rats with paroxetine nanoemulsion (administered intranasally) significantly improved the behavioural activities in comparison to paroxetine suspension (orally administered). Biochemical estimation results revealed that the prepared nanoemulsion was effective in enhancing the depressed levels of glutathione and decreasing the elevated levels of TBARS.

  7. ORGANIZATION OF PUBLIC ADMINISTRATION

    OpenAIRE

    Mrkša, Jožica

    2012-01-01

    In the thesis titled Organization of Public Administration I concentrated in the review of national and foreign literature. My decision for this topic is based on the personal interest and relevance of the topic in this particular period of time. The purpose of my work was to present the public administration in general, with focus in public administration of Slovenia. At first, the theoretical background of public administration is presented, with following topics addressed: public administr...

  8. Gelatin nanoparticles for use as a vaccine adjuvant in intranasal immunizations

    Science.gov (United States)

    Washington, Tara D.

    Vaccine adjuvants are used to increase the immune response in the delivery of subunit antigens. Currently the only FDA approved adjuvants are aluminum based and must be delivered parenterally. Nasal mucoadhesive vaccine administration can decrease cost, increase efficiency and increase patient compliance. The purpose of this study was to develop a mucoadhesive gelatin nanoparticle >500 nm in diameter that can be used to encapsulate a model protein antigen. The particles were prepared by nanoprecipitation of a gelatin solution with acetone. Thiol groups were incubated with gelatin to increase mucoadhesivness at 20, 40, and 80 mg per 1 gram of gelatin. The thiolation chemistry was characterized using UV-Vis and x-ray photoelectron spectroscopy (XPS). The total amount of sulfur present in the gelatin was determined to be 7.48, 30.53, and 46.75 mmol/gram respectively. However XPS analysis revealed that there was no substantial difference between surface sulfur content of the unmodified gelatin nanoparticles and the gelatin nanoparticles modified with 80 mg of iminothiolane. Particle size, charge and morphology were determined using laser light diffraction, atomic force microscopy microscopy and electron microscopy. The average diameter of the unmodified gelatin was 171 nm. The average diameter of the thiolated gelatin nanoparticles was 275 nm. The polydispersity index was approximately 0.61 +/- 0 .04 for all nanoparticles. The zeta (zeta) potential of the unmodified gelatin nanoparticles was -21.5 +/- 2.0 mV and the zeta-potential of the modified gelatin nanoparticles was -25.2 +/- 1.5, -27.3 +/- 0.8, and -28.6 +/- 3.0 mV for the 20, 40, and 80 thiolated gelatin nanoparticles. Particle encapsulation efficiency (EE) and release kinetics were conducted using fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) as a model antigen. The EE of the nanoparticles increased from 35.0% (unmodified gelatin) to 82.5% (highest modified gelatin). Particles encapsulated with

  9. Efeitos sedativos da associação de Cetamina e Midazolam administrados pela via intranasal ou intramuscular em papagaio (Amazona aestiva e Amazona vinacea

    Directory of Open Access Journals (Sweden)

    Eduarda H. Bitencourt

    2013-09-01

    Full Text Available A falta de protocolos de sedação seguros para uso em papagaios na literatura demonstra a necessidade de conhecer os anestésicos que são eficazes nestes animais. Devido a pouca massa muscular desta espécie, notou-se a necessidade de estudar outra via de administração, menos invasiva e dolorosa ao animal, como a via intranasal. O objetivo deste estudo foi avaliar os efeitos sedativos e a viabilidade da administração intranasal, em comparação à via intramuscular, de 15mg/kg de Cetamina e 1mg/kg de Midazolam. Foram utilizados 14 papagaios das espécies Amazona aestiva e Amazona vinacea, de ambos os sexos, adultos, peso médio de 388,5±29,1g. Os animais foram distribuídos aleatoriamente em dois grupos: intramuscular (IM, n=7 e intranasal (IN, n=7. No grupo intramuscular, a administração dos anestésicos foi realizada nos músculos peitorais, utilizando seringas de insulina e no grupo intranasal, com auxílio de uma micropipeta. Avaliou-se o período de latência, tempo de duração, qualidade de sedação, e o tempo de recuperação total. A média para o período de latência no grupo IM foi de 6,13±2,02 minutos e no grupo IN de 4,84±2,37 minutos. Já para o tempo de duração da sedação no grupo IM a média foi de 35,81±29,56 e no grupo IN de 24,52±14,83 minutos. Ambas as vias promoveram sedação adequada, pois a média do escore da qualidade de sedação obtida pelo grupo IM foi 2±1,5 e pelo grupo IN 1,28±1,1. O tempo de recuperação total no grupo IM foi de 27,04±11,69 e no grupo IN de 17,67±11,64 minutos. Apesar do grupo IN ter apresentado os menores tempos de período de latência, duração e de recuperação total e ter obtido melhor escore na qualidade de sedação, não houve diferença estatística significativa entre os grupos. Os resultados obtidos neste estudo indicam que a administração de 15 mg/kg de cetamina e 1mg/kg de midazolam pela via intranasal ou intramuscular em papagaios (Amazona aestiva e

  10. Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.

    Science.gov (United States)

    Krishnan, Vyjayanthi; Andersen, Bo H; Shoemaker, Christine; Sivko, Gloria S; Tordoff, Kevin P; Stark, Gregory V; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew; Roberts, M Scot

    2015-04-01

    AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. PMID:25673303

  11. Allergen-specific regulation of allergic rhinitis in mice by intranasal exposure to IgG1 monoclonal antibody Fab fragments against pathogenic allergen.

    Science.gov (United States)

    Matsuoka, Daiko; Mizutani, Nobuaki; Sae-Wong, Chutha; Yoshino, Shin

    2014-09-01

    Fab fragments (Fabs) have the ability to bind to specific antigens but lack the Fc portion for binding to receptors on immune and inflammatory cells that play a critical role in allergic diseases. In the present study, we investigated whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) inhibited allergic rhinitis in mice. BALB/c mice sensitized by intraperitoneal injections of ovalbumin (OVA) plus alum on days 0 and 14 were intranasally challenged with OVA on days 28-30, and 35. Fabs prepared by the digestion of an anti-OVA IgG1 mAb (O1-10) with papain were also intranasally administered 15min before each OVA challenge. The results showed that treatment with O1-10 Fabs significantly suppressed the sneezing frequency, associated with decrease of OVA-specific IgE in the serum and infiltration by mast cells in the nasal mucosa seen following the fourth antigenic challenge; additionally, the level of mouse mast cell protease-1, a marker of mast cell activation, in serum was decreased. Furthermore, infiltration of eosinophils and goblet cell hyperplasia in the nasal mucosa at the fourth challenge were inhibited by treatment with O1-10 Fabs. In conclusion, these results suggest that intranasal exposure to Fabs of a pathogenic antigen-specific IgG1 mAb may be effective in regulating allergic rhinitis through allergen capture by Fabs in the nasal mucosa before the interaction of the intact antibody and allergen.

  12. Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy.

    Science.gov (United States)

    Carvalho, Flávia Chiva; Campos, Michel Leandro; Peccinini, Rosângela Gonçalves; Gremião, Maria Palmira Daflon

    2013-05-01

    The purpose of this study was to develop a mucoadhesive stimuli-sensitive drug delivery system for nasal administration of zidovudine (AZT). The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior. Flow rheology measurements showed that the formulation composed of PPG-5-CETETH-20, oleic acid and water (55, 30, 15% w/w), denominated P, has Newtonian flow behavior. Polarized light microscopy (PLM) revealed that formulation P is isotropic, whereas its 1:1 (w/w) dilution with artificial nasal mucus (ANM) changed the system to an anisotropic lamellar phase (PD). Oscillatory frequency sweep analysis showed that PD has a high storage modulus (G') at nasal temperatures. Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion. Ex vivo permeation studies across porcine nasal mucosa exhibited an 18-fold rise in the permeability of AZT from the formulation. The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms. Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG-5-CETETH-20, oleic acid, and water formulation could form a mucoadhesive matrix in contact with nasal mucus that promoted nasal absorption of the AZT. For an in vivo assessment, the plasma concentrations of AZT in rats were determined by HPLC method following intravenous and intranasal administration of AZT-loaded P formulation (PA) and AZT solution, respectively, at a dose of 8mg/kg. The intranasal administration of PA resulted in a fast absorption process (Tmax=6.7min). Therefore, a liquid crystal precursor formulation administered by the nasal route might represent a promising novel tool for the systemic delivery of AZT and other antiretroviral drugs. In the present study, the uptake of AZT absorption in the nasal mucosa was

  13. Protection against Chlamydia promoted by a subunit vaccine (CTH1 compared with a primary intranasal infection in a mouse genital challenge model.

    Directory of Open Access Journals (Sweden)

    Anja Weinreich Olsen

    Full Text Available BACKGROUND: The chlamydial proteins CT443 (OmcB and CT521 (rl16 have previously been identified as human B and/or T cell targets during a chlamydial infection in humans. Here we compare the protective effector mechanism promoted by a fusion protein composed of CT521 and CT443 (CTH1 with a primary intranasal Chlamydia muridarum infection known to provide high levels of protection against a genital chlamydial challenge. METHODOLOGY/PRINCIPAL FINDINGS: The fusion protein CTH1, adjuvanted with a strong Th1 inducing cationic adjuvant (CAF01, significantly reduced the bacterial shedding compared to a control group in both a C. trachomatis Serovar D and C. muridarum challenge model. The CTH1/CAF01 vaccine was found to induce polyfunctional T cells consisting of TNFalpha/IL-2 and TNFalpha/IL-2/IFN-gamma positive cells and high titers of CTH1 specific IgG2a and IgG1. By depletion experiments the protection in the C. muridarum challenge model was demonstrated to be mediated solely by CD4(+ T cells. In comparison, an intranasal infection with C. muridarum induced a T cell response that consisted predominantly of TNFalpha/IFN-gamma co-expressing effector CD4(+ T cells and an antibody response consisting of C. muridarum specific IgG1, IgG2a but also IgA. This response was associated with a high level of protection against challenge-a protection that was only partially dependent on CD4(+ T cells. Furthermore, whereas the antibody response induced by intranasal infection was strongly reactive against the native antigens displayed in the chlamydial elementary body, only low levels of antibodies against this preparation were found after CTH1/CAF01 immunization. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that CTH1 vaccination promotes a CD4(+ T cell dependent protective response but compared with intranasal C. muridarum infection lacks a CD4 independent protective mechanism for complete protection.

  14. Transportation Security Administration

    Science.gov (United States)

    ... content Official website of the Department of Homeland Security Transportation Security Administration A - Z Index What Can I Bring? Search form Apples Main menu Administrator Travel Security Screening Special Procedures TSA Pre✓® Passenger Support Travel ...

  15. Cloudera administration handbook

    CERN Document Server

    Menon, Rohit

    2014-01-01

    An easy-to-follow Apache Hadoop administrator's guide filled with practical screenshots and explanations for each step and configuration. This book is great for administrators interested in setting up and managing a large Hadoop cluster. If you are an administrator, or want to be an administrator, and you are ready to build and maintain a production-level cluster running CDH5, then this book is for you.

  16. Understanding land administration systems

    OpenAIRE

    P. Williamson, Ian; Enemark, Stig; Wallace, Judy; Rajabifard, Abbas

    2008-01-01

    This paper introduces basic land administration theory and highlights four key concepts that are fundamental to understanding modern land administration systems - firstly the land management paradigm and its influence on the land administration framework, secondly the role that the cadastre plays in contributing to sustainable development, thirdly the changing nature of ownership and the role of land markets, and lastly a land management vision that promotes land administration in support of ...

  17. Refinement for administrative policies

    OpenAIRE

    Dekker, M.A.C.; Etalle, S.

    2007-01-01

    Flexibility of management is an important requisite for access control systems as it allows users to adapt the access control system in accordance with practical requirements. This paper builds on earlier work where we defined administrative policies for a general class of RBAC models. We present a formal definition of administrative refinnement and we show that there is an ordering for administrative privileges which yields administrative refinements of policies. We argue (by giving an examp...

  18. Low pH gel intranasal sprays inactivate influenza viruses in vitro and protect ferrets against influenza infection

    Directory of Open Access Journals (Sweden)

    Lambkin-Williams Robert

    2007-05-01

    Full Text Available Abstract Background Developing strategies for controlling the severity of pandemic influenza is a global public health priority. In the event of a pandemic there may be a place for inexpensive, readily available, effective adjunctive therapies to support containment strategies such as prescription antivirals, vaccines, quarantine and restrictions on travel. Inactivation of virus in the intranasal environment is one possible approach. The work described here investigated the sensitivity of influenza viruses to low pH, and the activity of low pH nasal sprays on the course of an influenza infection in the ferret model. Methods Inactivation of influenza A and avian reassortment influenza was determined using in vitro solutions tests. Low pH nasal sprays were tested using the ferret model with an influenza A Sydney/5/97 challenge. Clinical measures were shed virus, weight loss and body temperature. Results The virus inactivation studies showed that influenza viruses are rapidly inactivated by contact with acid buffered solutions at pH 3.5. The titre of influenza A Sydney/5/97 [H3N2] was reduced by at least 3 log cycles with one minute contact with buffers based on simple acid mixtures such as L-pyroglutamic acid, succinic acid, citric acid and ascorbic acid. A pH 3.5 nasal gel composition containing pyroglutamic acid, succinic acid and zinc acetate reduced titres of influenza A Hong Kong/8/68 [H3N2] by 6 log cycles, and avian reassortment influenza A/Washington/897/80 X A Mallard/New York/6750/78 [H3N2] by 5 log cycles, with 1 min contact. Two ferret challenge studies, with influenza A Sydney/5/97, demonstrated a reduction in the severity of the disease with early application of low pH nasal sprays versus a saline control. In the first study there was decreased weight loss in the treatment groups. In the second study there were reductions in virus shedding and weight loss, most notably when a gelling agent was added to the low pH formulation

  19. Intranasal “painless” Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice

    Science.gov (United States)

    Capsoni, Simona; Marinelli, Sara; Ceci, Marcello; Vignone, Domenico; Amato, Gianluca; Malerba, Francesca; Paoletti, Francesca; Meli, Giovanni; Viegi, Alessandro; Pavone, Flaminia; Cattaneo, Antonino

    2012-01-01

    Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that “painless” hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of “painless” hNGF variants as a new generation of therapeutics for neurodegenerative diseases. PMID:22666365

  20. Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

    Directory of Open Access Journals (Sweden)

    Pan L

    2014-12-01

    Full Text Available Li Pan,1,2 Zhongwang Zhang,1,2 Jianliang Lv,1,2 Peng Zhou,1,2 Wenfa Hu,1,2 Yuzhen Fang,1,2 Haotai Chen,1,2 Xinsheng Liu,1,2 Junjun Shao,1,2 Furong Zhao,1,2 Yaozhong Ding,1,2 Tong Lin,1,2 Huiyun Chang,1,2 Jie Zhang,1,2 Yongguang Zhang,1,2 Yonglu Wang1,2 1State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS, Lanzhou, Gansu, People’s Republic of China; 2Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China Abstract: The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD. In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1 chitosan-coated poly(lactic-co-glycolic acid (PLGA loaded with plasmid DNA (Chi-PLGA-DNA and (2 chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV (Chi-Tre-Inactivated. Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (IgA (sIgA antibodies in nasal washes were initially detected at 4 days postvaccination (dpv with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with

  1. Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study.

    Science.gov (United States)

    Madane, Rohini G; Mahajan, Hitendra S

    2016-05-01

    Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as a carrier for curcumin (CRM). The CRM-loaded NLC developed as a particle with the size of 146.8 nm, a polydispersity index of 0.18, an entrapment efficiency (EE) of 90.86%, and the zeta potential (ZP) of -21.4 mV. Besides, the increased cytotoxicity of CRM-NLC than that of CRM to astrocytoma-glioblastoma cell line (U373MG) in the cancer cell lines was observed. Results of biodistribution studies showed higher drug concentration in brain after intranasal administration of NLCs than PDS. The results of the study also suggest that CRM-NLC is a promising drug delivery system for brain cancer therapy. PMID:25367836

  2. Personality Traits and Administrators

    OpenAIRE

    Anitha V

    2008-01-01

    Administration is the art of getting tasks done by utilizing the resources and coordinating the people. Administrators give trigger to the administration by coordinating, and directing all parts of an organization by managing the tangible and intangible resources of the organization. The qualities of leadership are therefore a critical determinant of organizational success. The theories of leadership (Trait to Transformational leadership theory) have strived to look into the aspects that make...

  3. Veterans Administration Databases

    Science.gov (United States)

    The Veterans Administration Information Resource Center provides database and informatics experts, customer service, expert advice, information products, and web technology to VA researchers and others.

  4. Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Zhou Xing

    Full Text Available BACKGROUND: Recombinant adenovirus-vectored (Ad tuberculosis (TB vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. METHODS AND FINDINGS: Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n, AdAg85A intramuscularly (i.m, BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb. At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. CONCLUSIONS: Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.

  5. Effects of nasal administration or subcutaneous injection of testosterone/testosterone propionate on expression efficacy of c-Fos in rat brain%经鼻及皮下给予睾丸酮/丙酸睾丸酮对大鼠相关脑区c-Fos表达效能的影响

    Institute of Scientific and Technical Information of China (English)

    张国梁; 牛小龙; 康云霄; 薛岩; 方卉; 石葛明

    2013-01-01

    Objective:To explore the efficacy of intranasal administration or subcutaneous injection of testosterone (T) / testosterone propionate (TP) on different brain regions in rats. Methods:Radioimmunoassay was used to detect testosterone concentration in cerebrospinal fluid and in serum after intranasal administration of TP. Immunohistochemistry was used to detect the expression of c-Fos protein in different brain regions. Results:Testosterone in cerebrospinal fluid and in serum was decreased in gonadectomized (GDX) rats compared to the normal control rats. Subcutaneous injection of TP in GDX rats only increased testosterone in serum. Testosterone in cerebrospinal fluid and in serum was increased after intranasal administration of TP in GDX rats and in the normal control rats. Testosterone in cerebrospinal fluid of GDX rats after intranasal administration of TP was higher than that in GDX rats after subcutaneous injection of TP, however testosterone in serum of GDX rats after intranasal administration of TP was lower than that in GDX rats after subcutaneous injection of TP. After intranasal administration of TP or T, the number of c-Fos-immunoreactive cells and the c-Fos immunoreactive intensity were increased in more brain regions. However, after subcutaneous injection of TP, the number of c-Fos-immunoreactive cells and the c-Fos immunoreactive intensity were increased only in a few brain regions. Conclusion:Intranasal administration of TP or T could induce the expression of c-Fos and activate more brain regions. That can provide a new therapy method for some central nervous system diseases.%目的:探讨经鼻和皮下给予睾丸酮(T)或丙酸睾丸酮(TP)对大鼠中枢神经系统相关脑区激活的效能.方法:利用放射免疫分析法检测大鼠经鼻滴注给予TP后脑脊液和血清睾丸酮浓度的变化;以免疫组织化学观察大鼠各脑区cFos的表达.结果:放射免疫结果显示去势组大鼠脑脊液和血清中睾丸酮含量比正

  6. CDS - Database Administrator's Guide

    Science.gov (United States)

    Day, J. P.

    This guide aims to instruct the CDS database administrator in: o The CDS file system. o The CDS index files. o The procedure for assimilating a new CDS tape into the database. It is assumed that the administrator has read SUN/79.

  7. Webmin administrator's cookbook

    CERN Document Server

    Karzynski, Michal

    2014-01-01

    Written in a cookbook format with practical recipes this book helps you to perform various administrative tasks using Webmin and enables you to perform common jobs more efficiently.This book is perfect for System administrators who want to learn more advanced concepts of Webmin and how it can help to set up a server for development, testing or deployment.

  8. Understanding land administration systems

    DEFF Research Database (Denmark)

    P. Williamson, Ian; Enemark, Stig; Wallace, Judy;

    2008-01-01

    This paper introduces basic land administration theory and highlights four key concepts that are fundamental to understanding modern land administration systems. Readers may recall the first part of the paper in October issue of Coordinates. Here is the concluding part that focuses on the changing...... role of ownership and the role of land markets. Udgivelsesdato: November...

  9. Oral administration of taxanes

    NARCIS (Netherlands)

    Malingré, M.M.

    2002-01-01

    Oral treatment with cytotoxic agents is to be preferred as this administration route is convenient to patients, reduces administration costs and facilitates the use of more chronic treatment regimens. For the taxanes paclitaxel and docetaxel, however, low oral bioavailability has limited development

  10. Administration for Student Development.

    Science.gov (United States)

    Bergen, J. J., Ed.

    This collection of papers focuses on school administration and its relation to students. It is contended that toay's student matures earlier; has higher expectations; is more affluent; is more isolated from adults; is more critical and outspoken; and, therefore, must be heard by teachers and administrators. A related document is EA 001578.…

  11. The School Personnel Administrator.

    Science.gov (United States)

    Knox, Rodney F.

    This paper provides an overview of the development of the school-personnel administrator role. It first describes the influence of the science-management and human-relations movements and the behavioral sciences on personnel administration and human resource management. It next discusses the role of the personnel-performance-appraisal system and…

  12. Postmodern Public Administration

    DEFF Research Database (Denmark)

    Bogason, Peter

    2005-01-01

    Discussion of the trends towards more uses of postmodern analysis within the discipline of public administration, particularly in the USA......Discussion of the trends towards more uses of postmodern analysis within the discipline of public administration, particularly in the USA...

  13. Centos system administration essentials

    CERN Document Server

    Mallett, Andrew

    2014-01-01

    If you are a Linux administrator who is looking to gain knowledge that differentiates yourself from the crowd, then this is the book for you. Beginners who have a keen interest to learn more about Linux administration will also progress quickly with this resourceful learning guide.

  14. Administration and Jurisdictional Policy

    Directory of Open Access Journals (Sweden)

    Eduardo Hernando Nieto

    2009-06-01

    Full Text Available To what extent does studying jurisdictional politics need the knowledge of different administrative theories in general and the science of public administration in particular? This small text proposes such reflection and comes to the conclusion that it is impossible to propose a new approximation to this topic without considering the administrative theory, for that the specialists and thinkers will get more with the contact of this discipline from what it is called a multidisciplinary approach.

  15. Publication of administrative circular

    CERN Multimedia

    HR Department

    2009-01-01

    ADMINISTRATIVE CIRCULAR NO. 23 (REV. 2) – SPECIAL WORKING HOURS Administrative Circular No. 23 (Rev. 2) entitled "Special working hours", approved following discussion in the Standing Concertation Committee on 9 December 2008, will be available on the intranet site of the Human Resources Department as from 19 December 2008: http://cern.ch/hr-docs/admincirc/admincirc.asp It cancels and replaces Administrative Circular No. 23 (Rev. 1) entitled "Stand-by duty" of April 1988. A "Frequently Asked Questions" information document on special working hours will also be available on this site. Paper copies of this circular will shortly be available in Departmental Secretariats. Human Resources Department Tel. 78003

  16. PUBLICATION OF ADMINISTRATIVE CIRCULAR

    CERN Multimedia

    HR Department

    2008-01-01

    ADMINISTRATIVE CIRCULAR NO. 23 (REV. 2) – SPECIAL WORKING HOURS Administrative Circular No. 23 (Rev. 2) entitled "Special working hours", approved following discussion in the Standing Concertation Committee meeting of 9 December 2008, will be available on the intranet site of the Human Resources Department as from 19 December 2008: http://cern.ch/hr-docs/admincirc/admincirc.asp It cancels and replaces Administrative Circular No. 23 (Rev. 1) entitled "Stand-by duty" of April 1988. A "Frequently Asked Questions" information document on special working hours will also be available on this site. Paper copies of this circular will shortly be available in departmental secretariats. Human Resources Department Tel. 78003

  17. Veterans Health Administration (VHA)

    Data.gov (United States)

    Social Security Administration — The purpose of this agreement is for SSA to verify SSNs and other identifying information for the Department of Veterans Affairs, VHA. DVA will use the information...

  18. Humanism, Administration and Education

    DEFF Research Database (Denmark)

    Plum, Maja

    2012-01-01

    Abstract Through the example of a Danish reform of educational plans in early childhood education, this paper analyses the emergence of a new pedagogical desire related to administrative educational reforms promoting accountability, visibility and documentation. Two arguments are made: first......, it is argued that the changes in administrative practices during the last decade constitute a transformation, but also a reproduction of relations between knowledge and governing that goes back to the big expansion of the welfare state. Second, it is argued that these relations between knowledge and governing...... are not restricted to the administrative practices, but are part of education and its humanistic legacy as well. As such, the administrative demand of documentation becomes possible and recognisable through its reproductive elements. Elements that are constituted in a transformative conjunction in which...

  19. Administrative & Operational Circulars - Reminder

    CERN Multimedia

    HR Department

    2011-01-01

    All Administrative and Operational Circulars are available on the intranet site of the Human Resources Department at the following address: http://cern.ch/hr-docs/admincirc/admincirc.asp Department Head Office  

  20. Understanding land administration systems

    DEFF Research Database (Denmark)

    P. Williamson, Ian; Enemark, Stig; Wallace, Judy;

    2008-01-01

    in contributing to sustainable development, thirdly the changing nature of ownership and the role of land markets, and lastly a land management vision that promotes land administration in support of sustainable development and spatial enablement of society. We present here the first part of the paper. The second...... part focuses on the changing  role of ownership and the role of land markets, and a land management vision will be published in November issue of Coordinates. Udgivelsesdato: Oktober......This paper introduces basic land administration theory and highlights four key concepts that are fundamental to understanding modern land administration systems - firstly the land management paradigm and its influence on the land administration framework, secondly the role that the cadastre plays...

  1. Social Security Administration

    Science.gov (United States)

    ... Languages Sign in / up The United States Social Security Administration Cost-Of-Living Adjustment (COLA) Information about ... replacement Medicare card Change of Address my Social Security Check out your Social Security Statement , change your ...

  2. Administrative Discretionary Grant Data

    Data.gov (United States)

    Institute of Museum and Library Services — This dataset of administrative records contains discretionary grant recipients who were awarded funds by the Institute of Museum and Library Services from fiscal...

  3. Spatially enabled land administration

    DEFF Research Database (Denmark)

    Enemark, Stig

    2006-01-01

    enabling of land administration systems managing tenure, valuation, planning, and development will allow the information generated by these activities to be much more useful. Also, the services available to private and public sectors and to community organisations should commensurably improve. Knowledge....... In other words: Good governance and sustainable development is not attainable without sound land administration or - more broadly – sound land management. The paper presents a land management vision that incorporates the benefits of ICT enabled land administration functions. The idea is that spatial...... the communication between administrative systems and also establish more reliable data due to the use the original data instead of copies. In Denmark, such governmental guidelines for a service-oriented ITarchitecture in support of e-government are recently adopted. Finally, the paper presents the role of FIG...

  4. SELinux policy administration

    CERN Document Server

    Vermeulen, Sven

    2013-01-01

    A step-by-step guide to learn how to set up security on Linux servers by taking SELinux policies into your own hands.Linux administrators will enjoy the various SELinux features that this book covers and the approach used to guide the admin into understanding how SELinux works. The book assumes that you have basic knowledge in Linux administration, especially Linux permission and user management.

  5. Learning Cassandra for administrators

    CERN Document Server

    Parthasarathy, Vijay

    2013-01-01

    This book is a practical, hands-on guide, taking the reader from the basics of using Cassandra though to the installation and the running.Learning Cassandra for Administrators is for administrators who manage a large deployment of Cassandra clusters, and support engineers who would like to install the monitoring tools and who are also in charge of making sure the cluster stays the same, ensuring that the service is always up and running.

  6. Education of System Administration

    OpenAIRE

    Feyrer, Hubert

    2007-01-01

    This article discusses education of system administration. Theoretical foundations cover psychology, learning theory, instruction theory, and instructional design, leading to an ideal progression for education, and related tools. The main part describes an existing class on system administration as given at the University of Applied Sciences (Fachhochschule, FH) Regensburg, Germany. It is analyzed for its history and target audience, the current curriculum, course layout, and for the didac...

  7. Administration for Defence Scientists

    Directory of Open Access Journals (Sweden)

    G. E. Gale

    1953-01-01

    Full Text Available All scientific work must be carried out against a background of adequate administrative support if it is to become effective and produce useful results. Administration is not a job for which we, as scientists, are particularly trained; and it is a thing of which we tend to fight shy, partly because, author suppose, most Of peoples are associate the administrator with highly unpleasant matters such as income tax, delays in getting our pay cheques, and so on - For that reason we do not feel, always pay  sufficient attention to administrative affairs ; rather like the ostrich, we try to escape from them by merely ignoring them. But that is a wrong and unfruitful attitude to adopt. All live so much under the activities of the trained administrator that should, if, it  give a great deal of thought to our own administrative problems deliberate and conscious thought to them-and make an honest and heart-searching self analysis regarding our own possible failings.

  8. Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism.

    Science.gov (United States)

    Watanabe, Takamitsu; Kuroda, Miho; Kuwabara, Hitoshi; Aoki, Yuta; Iwashiro, Norichika; Tatsunobu, Natsubori; Takao, Hidemasa; Nippashi, Yasumasa; Kawakubo, Yuki; Kunimatsu, Akira; Kasai, Kiyoto; Yamasue, Hidenori

    2015-11-01

    Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies.

  9. Nasal administration of morphine-6-glucuronide in sheep--a pharmacokinetic study.

    Science.gov (United States)

    Illum, L; Davis, S S; Pawula, M; Fisher, A N; Barrett, D A; Farraj, N F; Shaw, P N

    1996-11-01

    The pharmacokinetics of morphine-6-glucuronide (M6G) after both intravenous dosing and nasal administration were studied in sheep. The nasal formulation consisted of M6G in combination with an absorption promoting delivery system in the form of chitosan. The mean half-life of M6G after intravenous administration was 51.0 +/- 8.2 min and that after intranasal dosing was 45.0 +/- 5.5 min. M6G clearance and volume of distribution were 5.4 +/- 1.5 mL min-1 kg-1 and 0.4 +/- 0.1 L kg-1 respectively. The plasma profile after nasal administration demonstrated rapid absorption of M6G. The bioavailability of M6G in the chitosan formulation was found to be 31.4%. These results suggest that M6G administered in combination with the chitosan delivery system may be considered as a suitable non-parenteral means of administering this analgesic. PMID:8950049

  10. Nasal administration of ondansetron using a novel microspheres delivery system Part II: ex vivo and in vivo studies.

    Science.gov (United States)

    Mahajan, Hitendra S; Gattani, Surendra G

    2010-12-01

    Gellan gum-based mucoadhesive microspheres of ondansetron hydrochloride for intranasal systemic delivery were prepared to avoid first pass effect, an alternative route of administration to injection and to enhance systemic bioavailability of ondansetron hydrochloride. The microspheres were prepared using spray method. The evaluation results of microspheres were reported in our previous study. The aim of this work was to study the in vivo performance of mucoadhesive microspheres in comparison with oral and intravenous preparations of ondansetron hydrochloride. The nasal delivery system gave increased AUC(0-240) and C(max) as compared to those of oral delivery. In conclusion, the gellan gum-based microsphere formulation of ondansetron hydrochloride with mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption. PMID:20020823

  11. Behavioral Public Administration: Combining Insights from Public Administration and Psychology

    OpenAIRE

    Grimmelikhuijsen, Stephan; Jilke, Sebastian; Olsen, Asmus Leth; Tummers, Lars

    2015-01-01

    We propose behavioral public administration as a designated subfield in public administration which explicitly deals with the integration of theories and methods from psychology into the study of public administration. We discuss how scholars in public administration currently draw on both methodological and theoretical innovations in psychology and point to research questions in public administration which could benefit from further integration. Behavioral public administration cannot, and s...

  12. Pro Python System Administration

    CERN Document Server

    Sileika, R

    2010-01-01

    As time goes on, system administrators are presented with increasingly complicated challenges. In the early days, a team of engineers might have had to look after one or two systems. These days, one engineer can administer hundreds or thousands of systems. System administrators are gradually replacing their tools with more advanced and flexible ones. One of the choices is Python. Structurally, Python is a modern, high-level language with a very clean syntax. Python comes with many built-in libraries that can make automation tasks easier. It also has extensive set of third-party libraries and a

  13. Practical JIRA Administration

    CERN Document Server

    Doar, Matthew

    2011-01-01

    If you're familiar with JIRA for issue tracking, bug tracking, and other uses, you know it can sometimes be tricky to set up and manage. In this concise book, software toolsmith Matt Doar clarifies some of the more confusing aspects by answering difficult and frequently asked questions about JIRA administration. Practical JIRA Administration shows you how JIRA is intended to be used, making it an ideal supplement to the extensive documentation already available. The book's chapters are loosely connected, so you can go straight to the information that best serves your needs. Understand the di

  14. Computer hardware fault administration

    Science.gov (United States)

    Archer, Charles J.; Megerian, Mark G.; Ratterman, Joseph D.; Smith, Brian E.

    2010-09-14

    Computer hardware fault administration carried out in a parallel computer, where the parallel computer includes a plurality of compute nodes. The compute nodes are coupled for data communications by at least two independent data communications networks, where each data communications network includes data communications links connected to the compute nodes. Typical embodiments carry out hardware fault administration by identifying a location of a defective link in the first data communications network of the parallel computer and routing communications data around the defective link through the second data communications network of the parallel computer.

  15. Linux System Administration

    CERN Document Server

    Adelstein, Tom

    2007-01-01

    If you're an experienced system administrator looking to acquire Linux skills, or a seasoned Linux user facing a new challenge, Linux System Administration offers practical knowledge for managing a complete range of Linux systems and servers. The book summarizes the steps you need to build everything from standalone SOHO hubs, web servers, and LAN servers to load-balanced clusters and servers consolidated through virtualization. Along the way, you'll learn about all of the tools you need to set up and maintain these working environments. Linux is now a standard corporate platform with user

  16. Intranasal delivery of cationic PLGA nano/microparticles-loaded FMDV DNA vaccine encoding IL-6 elicited protective immunity against FMDV challenge.

    Directory of Open Access Journals (Sweden)

    Gang Wang

    Full Text Available Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing mucosal and systemic immune responses in animals. Three eukaryotic expression plasmids with or without bovine IL-6 gene (pc-P12A3C, pc-IL2AP12A3C and pc-P12AIL3C were generated. The two latter plasmids were designed with the IL-6 gene located either before or between the P12A and 3C genes, respectively, as a means of determining if the location of the IL-6 gene affected capsid assembly and the subsequent immune response. Guinea pigs and rats were intranasally vaccinated with the respective chitosan-coated PLGA nano/microparticles-loaded FMDV DNA vaccine formulations. Animals immunized with pc-P12AIL3C (followed by animals vaccinated with pc-P12A3C and pc-IL2AP12A3C developed the highest levels of antigen-specific serum IgG and IgA antibody responses and the highest levels of sIgA (secretory IgA present in mucosal tissues. However, the highest levels of neutralizing antibodies were generated in pc-IL2AP12A3C-immunized animals (followed by pc-P12AIL3C- and then in pc-P12A3C-immunized animals. pc-IL2AP12A3C-immunized animals also developed stronger cell mediated immune responses (followed by pc-P12AIL3C- and pc-P12A3C-immunized animals as evidenced by antigen-specific T-cell proliferation and expression levels of IFN-γ by both CD4+ and CD8+ splenic T cells. The percentage of animals protected against FMDV challenge following immunizations with pc-IL2AP12A3C, pc-P12AIL3C or pc-P12A3C were 3/5, 1/5 and 0/5, respectively. These data suggested that intranasal delivery

  17. Administration for Children and Families

    Science.gov (United States)

    ... Releases RSS Feeds Speeches Videos What is the Administration for Children & Families? The Administration for Children and Families (ACF) is a division ... more about the 100-day challenge Visit the Administration on Children, Youth and Families Website The Family ...

  18. Refinement for administrative policies

    NARCIS (Netherlands)

    Dekker, M.A.C.; Etalle, S.

    2007-01-01

    Flexibility of management is an important requisite for access control systems as it allows users to adapt the access control system in accordance with practical requirements. This paper builds on earlier work where we defined administrative policies for a general class of RBAC models. We present a

  19. Refinement for Administrative Policies

    NARCIS (Netherlands)

    Dekker, M.A.C.; Etalle, S.

    2007-01-01

    Flexibility of management is an important requisite for access control systems as it allows users to adapt the access control system in accordance with practical requirements. This paper builds on earlier work where we defined administrative policies for a general class of RBAC models. We present a

  20. United States Fire Administration

    Science.gov (United States)

    ... Reduction: Getting the Most From the U.S. Fire Administration’s Daily National Operations Brief PDF 127 KB There ... staff. Follow us: Twitter Facebook YouTube U.S. Fire Administration 16825 S. Seton Ave. , Emmitsburg , MD 21727 USA 800‑ ...

  1. Educational Administration's Weber.

    Science.gov (United States)

    Gronn, Peter

    1994-01-01

    Discusses Max Weber's importance in Greenfield's work, particularly in Greenfield and Ribbins'"Greenfield on Educational Administration" (1993). In concentrating on human actors' subjective understanding, Greenfield was a faithful Weberian. However, he deviated from Weber by disavowing structural explanations of social and organizational…

  2. Urban School Administration.

    Science.gov (United States)

    McKelvey, Troy V., Ed.; Swanson, Austin D., Ed.

    This document contains 12 papers presented at an institute for urban school administrators designed to deal with the contemporary urban educational problems incident to school desegregation, social integration, and the equality of educational opportunity. The authors of the papers relate recent research findings to practical field experience, and…

  3. IVA: Improving Vocational Administration.

    Science.gov (United States)

    EPD Consortium D, Richardson, TX.

    These six instructional units are intended to provide instructors of vocational education administration with a systematic package of materials for their programs of preservice and/or inservice instruction and to provide materials which could be reproduced for learner use. These units cover the following subject matter: (1) federal legislation…

  4. Administrators Confront Student "Sexting"

    Science.gov (United States)

    Manzo, Kathleen Kennedy

    2009-01-01

    Cellphone-savvy students have created instructional and disciplinary challenges for educators for years. But the recent emergence of "sexting" by adolescents over their mobile phones caught many school administrators off guard, and the practice is prompting efforts around the country to craft policy responses. Students' sharing of nude or…

  5. A Treatise on Administration.

    Science.gov (United States)

    Moore, Thomas R.

    1988-01-01

    Expands Henri Fayol's definition of the administrative process to include a humanistic approach involving planning, organizing, implementing, controlling, evaluating, and satisfying functions. This empirical definition differs from some theoretical approaches by looking beyond resource consumption to consider ecological effects on the environment…

  6. Enterprise Mac administrators guide

    CERN Document Server

    Smith, William

    2015-01-01

    IT departments everywhere will be integrating Macs and Mac OS X into their IT infrastructure and this book will tell them how to do it. It will serve as an authoritative, useful and frequently referenced book on Mac OS X administration.

  7. Behavioral Public Administration: Combining Insights from Public Administration and Psychology

    DEFF Research Database (Denmark)

    Grimmelikhuijsen, Stephan; Jilke, Sebastian; Olsen, Asmus Leth;

    2015-01-01

    We propose behavioral public administration as a designated subfield in public administration which explicitly deals with the integration of theories and methods from psychology into the study of public administration. We discuss how scholars in public administration currently draw on both...... methodological and theoretical innovations in psychology and point to research questions in public administration which could benefit from further integration. Behavioral public administration cannot, and should not, replace ‘conventional’ public administration, but it is complementary to it. Importantly......, behavioral public administration represents a two-way street in which public administration scholars use theories and methods from psychology, and psychologists, in turn, learn from our setting of political-administrative contexts to refine their theories and methods. Finally, we propose four principals...

  8. Use of a Guinea pig-specific transcriptome array for evaluation of protective immunity against genital chlamydial infection following intranasal vaccination in Guinea pigs.

    Directory of Open Access Journals (Sweden)

    Shradha Wali

    Full Text Available Guinea pigs have been used as a second animal model to validate putative anti-chlamydial vaccine candidates tested in mice. However, the lack of guinea pig-specific reagents has limited the utility of this animal model in Chlamydia sp. vaccine studies. Using a novel guinea pig-specific transcriptome array, we determined correlates of protection in guinea pigs vaccinated with Chlamydia caviae (C. caviae via the intranasal route, previously reported by us and others to provide robust antigen specific immunity against subsequent intravaginal challenge. C. caviae vaccinated guinea pigs resolved genital infection by day 3 post challenge. In contrast, mock vaccinated animals continued to shed viable Chlamydia up to day 18 post challenge. Importantly, at day 80 post challenge, vaccinated guinea pigs experienced significantly reduced genital pathology - a sequelae of genital chlamydial infections, in comparison to mock vaccinated guinea pigs. Sera from vaccinated guinea pigs displayed antigen specific IgG responses and increased IgG1 and IgG2 titers capable of neutralizing GPIC in vitro. Th1-cellular/inflammatory immune genes and Th2-humoral associated genes were also found to be elevated in vaccinated guinea pigs at day 3 post-challenge and correlated with early clearance of the bacterium. Overall, this study provides the first evidence of guinea pig-specific genes involved in anti-chlamydial vaccination and illustrates the enhancement of the utility of this animal model in chlamydial pathogenesis.

  9. Clinical effects of topical antifungal therapy in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial of intranasal fluconazole

    Science.gov (United States)

    Hashemian, Farshad; Hashemian, Farnaz; Molaali, Najmeh; Rouini, Mohammadreza; Roohi, Elnaz; Torabian, Saadat

    2016-01-01

    Several studies have been in favor of fungi as a possible pathogenesis of chronic rhinosinusitis (CRS); however, to date, there is no scientific consensus about the use of antifungal agents in disease management. The aim of the present study was to investigate the efficacy of intranasal fluconazole in improving disease symptoms and objective outcomes of patients with CRS. A randomized, double-blind, placebo-controlled study was conducted on 54 patients who were diagnosed with CRS and had not been responsive to routine medical treatments. They were randomly assigned to receive either fluconazole nasal drop 0.2 % or placebo in addition to the standard regimen for a duration of 8 weeks. Patients' outcomes were evaluated according to Sino-Nasal Outcome Test 20 (SNOT-20), endoscopic scores, and Computed Tomography (CT) scores. No statistically significant difference was found in SNOT-20 (p = 0.201), endoscopic (p = 0.283), and CT scores (p = 0.212) of the patients at baseline and after 8-week course of treatment between drug and placebo group. Similar to many studies, the use of topical antifungal treatment for patients with CRS was not shown to be significantly effective. However, further studies are needed to obtain high levels of consistent evidence in order to arrive at a decision whether antifungal therapy is effective in management of CRS or not. PMID:27065776

  10. Intranasal immunization with fusion protein MrpH·FimH and MPL adjuvant confers protection against urinary tract infections caused by uropathogenic Escherichia coli and Proteus mirabilis.

    Science.gov (United States)

    Habibi, Mehri; Asadi Karam, Mohammad Reza; Shokrgozar, Mohammad Ali; Oloomi, Mana; Jafari, Anis; Bouzari, Saeid

    2015-04-01

    Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) and Proteus mirabilis are among the most common infections in the world. Currently there are no vaccines available to confer protection against UTI in humans. In this study, the immune responses and protection of FimH of UPEC with MrpH antigen of P. mirabilis in different vaccine formulations with and without MPL adjuvant were assessed. Mice intranasally immunized with the novel fusion protein MrpH·FimH induced a significant increase in IgG and IgA in serum, nasal wash, vaginal wash, and urine samples. Mice immunized with fusion MrpH·FimH also showed a significant boost in cellular immunity. Addition of MPL as the adjuvant enhanced FimH and MrpH specific humoral and cellular responses in both systemic and mucosal samples. Vaccination with MrpH·FimH alone or in combination with MPL showed the highest efficiency in clearing bladder and kidney infections in mice challenged with UPEC and P. mirabilis. These findings may indicate that the protection observed correlates with the systemic, mucosal and cellular immune responses induced by vaccination with these preparations. Our data suggest MrpH·FimH fusion protein with or without MPL as adjuvant could be potential vaccine candidates for elimination of UPEC and P. mirabilis. These data altogether are promising and these formulations are good candidates for elimination of UPEC and P. mirabilis.

  11. Land Administration Systems

    DEFF Research Database (Denmark)

    Enemark, Stig

    2014-01-01

    Land administration systems are the operational tool for conceptualizing rights, restrictions and responsibilities (RRRs) in land. Each of the rights, restrictions and responsibilities encompasses a human rights dimension that relates to the overall national land policies and should be unfolded as...... more than just rhetoric. This paper attempts to analyse the aspects of human rights in relation to land administration systems with a special focus on developing countries struggling to build adequate systems for governing the rights, restrictions and responsibilities in land. Human rights are the...... of being alive. Of special interest in relation to land and property is the right to own things and the right of food and adequate housing for all. More generally, human rights should be seen as an ethical responsibility of government to ensure that people enjoy some basic rights as human beings...

  12. Law Tackling Administrative Monopolies

    Institute of Scientific and Technical Information of China (English)

    WAN LIXIN

    2006-01-01

    @@ The long-anticipated anti-monopoly law needs to better address the crucial distinction between administrative and economic monopolies The first five months of 2oo6 saw a surge in the profits achieved by key State enterprises, especially in the eight sectors including petroleum, telecommunication and electricity, which achieved 285 billion yuan (US$36 billion) in profits, accounting for about 86 percent of the total, according to a July report. From the Stateowned Assets Supervision and Administration Commission of the State (SASAC). This news was both heartening and disquieting, for the most profitable sectors happen to be monopolistic enterprises, mostly upstream the production chain, who achieve their profitability at the expense of those companies further downstream. For years these sectors have been at the centre of the "bust-the-trust" storm.

  13. ATLAS TDAQ System Administration:

    CERN Document Server

    Lee, Christopher Jon; The ATLAS collaboration; Bogdanchikov, Alexander; Ballestrero, Sergio; Contescu, Alexandru Cristian; Dubrov, Sergei; Fazio, Daniel; Korol, Aleksandr; Scannicchio, Diana; Twomey, Matthew Shaun; Voronkov, Artem

    2015-01-01

    The ATLAS Trigger and Data Acquisition (TDAQ) system is responsible for the online processing of live data, streaming from the ATLAS experiment at the Large Hadron Collider (LHC) at CERN. The online farm is composed of ̃3000 servers, processing the data readout from ̃100 million detector channels through multiple trigger levels. During the two years of the first Long Shutdown (LS1) there has been a tremendous amount of work done by the ATLAS TDAQ System Administrators, implementing numerous new software applications, upgrading the OS and the hardware, changing some design philosophies and exploiting the High Level Trigger farm with different purposes. During the data taking only critical security updates are applied and broken hardware is replaced to ensure a stable operational environment. The LS1 provided an excellent opportunity to look into new technologies and applications that would help to improve and streamline the daily tasks of not only the System Administrators, but also of the scientists who wil...

  14. Moodle administration essentials

    CERN Document Server

    Henrick, Gavin

    2015-01-01

    If you are an experienced system administrator and know how to manage servers and set up web environments but now want to explore Moodle, this book is perfect for you. You'll get to grips with the basics and learn to manage Moodle quickly, focusing on essential tasks. Having prior knowledge of virtual learning environments would be beneficial, but is not mandatory to make the most of this book.

  15. Flexible Land Administration

    DEFF Research Database (Denmark)

    Enemark, Stig

    2014-01-01

    Security of tenure is widely considered to be the missing piece of the puzzle when it comes to eradication of poverty. And, as explained in the previous issue of Geoinformatics, the European Union is now placing land rights at the heart of EU development policy. This article presents a way forwar...... in terms of building flexible and "fit-for-purpose" land administration systems in developing countries. This will ensure security of tenure for all and sustainable management of the use of land....

  16. IPv6 Network Administration

    CERN Document Server

    Murphy, Niall Richard

    2009-01-01

    This essential guide explains what works, what doesn't, and most of all, what's practical about IPv6--the next-generation Internet standard. A must-have for network administrators everywhere looking to fix their network's scalability and management problems. Also covers other IPv6 benefits, such as routing, integrated auto-configuration, quality-of-services (QoS), enhanced mobility, and end-to-end security.

  17. Genesis of tax administration

    OpenAIRE

    Myskin, Y. I.

    2014-01-01

    The history of formation and development of tax administration is studied. The stages of genesis of tax administration are identified and described. The historically caused major trends in tax administration which are based on knowledge of the nature of causality are formulated. Досліджено історію становлення та розвитку управління оподаткуванням. Визначено та охарактеризовано етапи генезису управління оподаткуванням. На основі пізнання природи причинно-наслідкових зв’язків сфо...

  18. Oxytocin administration attenuates stress reactivity in borderline personality disorder: a pilot study.

    Science.gov (United States)

    Simeon, D; Bartz, J; Hamilton, H; Crystal, S; Braun, A; Ketay, S; Hollander, E

    2011-10-01

    Oxytocin has known stress-reducing and attachment-enhancing effects. We thus hypothesized that oxytocin would attenuate emotional and hormonal responses to stress in borderline personality disorder (BPD). Fourteen BPD and 13 healthy control (HC) adults received 40 IU intranasal oxytocin or placebo in double-blind randomized order followed by the Trier Social Stress Test. Subjective dysphoria (Profile of Mood Changes) and plasma cortisol levels were measured. Childhood trauma history, attachment style, and self-esteem were also rated. A significant "Group × Drug × Time" interaction effect for dysphoria (p=.04) reflected a proportionately greater attenuation of stress-induced dysphoria in the BPD group after oxytocin administration. Additionally, a marginally significant "Group × Drug" interaction effect for cortisol (p=.10) reflected a tendency toward greater attenuation of the stress-induced cortisol surge in the BPD group after oxytocin administration. In the combined sample, the oxytocin-placebo difference in the emotional stress reactivity was significantly predicted by childhood trauma alone (p=.037) and combined with self-esteem (p=.030), whereas the oxytocin-placebo difference in cortisol stress reactivity was predicted only by insecure attachment (p=.013). Results suggest that oxytocin may have a beneficial impact on emotional regulation in BPD, which merits further investigation and could have important treatment implications. PMID:21546164

  19. The Administration of Tax Systems

    OpenAIRE

    John Hasseldine

    2010-01-01

    This chapter analyses recent developments in tax administration and best practice. The chapter begins by contextualizing tax administration through a discussion on the necessary separation between the operational tasks performed in tax administration and the more generic, but nevertheless crucial, issues of organization, strategy and internal management required in tax administration. The chapter then describes the recent genesis and the current context of tax administration - especially in E...

  20. UML IN BUSINESS ADMINISTRATION

    OpenAIRE

    Daniel Ionita

    2010-01-01

    The article elaborates weather UML, primarily used in software engineering, can be a useful tool in business modeling and administration. By analyzing the advantages the modeling language has to offer we find that UML is visual and object oriented and that it is useful in expressing structure, interaction and behavior as well. With its help managers and business people can build models and diagrams to help put things into perspective. “Case Study 1” shows UML can be used as an analysis tool i...

  1. Does intranasal oxytocin promote prosocial behavior to an excluded fellow player? A randomized-controlled trial with Cyberball.

    Science.gov (United States)

    Riem, Madelon M E; Bakermans-Kranenburg, Marian J; Huffmeijer, Renske; van Ijzendoorn, Marinus H

    2013-08-01

    The neuropeptide oxytocin has been shown to stimulate prosocial behavior. However, recent studies indicate that adverse early caregiving experiences may moderate the positive effects of oxytocin. In this double blind randomized-controlled trial we investigated the effects of oxytocin on prosocial behavior during a virtual ball-tossing game called Cyberball. We examined the influence of oxytocin on prosocial helping behavior toward a socially excluded person who was known to the participant, taking into account early caregiving experiences and the emotional facial expression of the excluded person as potential moderators. Participants were 54 women who received a nasal spray containing either 16IU of oxytocin or a placebo and had reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that participants compensated for other players' ostracism by throwing the ball more often toward the excluded player. Oxytocin administration further increased the number of ball throws toward the excluded person, but only in individuals who experienced low levels of maternal love withdrawal. The facial expression of the excluded person did not affect prosocial helping behavior and did not moderate the effects of oxytocin. Our findings indicate that the positive effects of oxytocin on prosocial behavior toward a victim of social exclusion are limited to individuals with supportive family backgrounds. PMID:23352229

  2. Administration of Educational Services: A Glossary of Basic Administration Terminology.

    Science.gov (United States)

    Wheelbarger, J. J.

    From "achievement motivation" and "administration" to "Theory Z" and "viscidity and hedonic tone," this glossary defines 87 terms as they are used in educational administration. The terms include philosophical, psychological, organizational, and social concepts, but they all are employed in the theory and practice of administration. A short…

  3. Contact Center Manager Administration (CCMA)

    Data.gov (United States)

    Social Security Administration — CCMA is the server that provides a browser-based tool for contact center administrators and supervisors. It is used to manage and configure contact center resources...

  4. Administrative Law and Organization Theory

    Science.gov (United States)

    Evan, William M.

    1977-01-01

    Considered are some trends in American administrative law, some trends in organization theory, a model of the administrative process, and several potentially useful research strategies. The analysis has implications for comparative research on legal systems. (Author/LBH)

  5. Administrative Implications of Curriculum Reform

    Science.gov (United States)

    Abbott, Max G.; Eidell, Terry L.

    1970-01-01

    The director of the Center for the Advanced Study of Educational Administration at the University of Oregon and one of his associates discuss the new role of administration in an individual-oriented educational system. (AA)

  6. Functions Of Land Administration System

    OpenAIRE

    Oksana Sakal

    2012-01-01

    The theoretical basis and essence of some common and specific functions of land administration system as an integral mechanism of effective land use and land administration levels (case-study for forest and other land available for afforestation) are analysed.

  7. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Science.gov (United States)

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  8. Effect of Treatment with Intranasal Corticosteroid and Oral Antihistamine on Cytokine Profiles of Peripheral Blood Mononuclear Cells of Patients with Allergic Rhinitis Sensitive to Chenopodium album

    Directory of Open Access Journals (Sweden)

    Shokrollah Farrokhi

    2010-12-01

    Full Text Available Patients with allergic rhinitis (AR show increased production of the Th2-related cytokines. Almost always, intranasal corticosteroid (INC and antihistamine are used as routine therapy of AR. This study was performed to determine the in vitro secretion of cytokines profiles of PBMCs in patients with AR sensitive to Chenopodium album (Ch.a pollens before and after treatment with INC (Fluticasone propionate and oral antihistamine (Loratadine. PBMCs of 20 patients with AR, were tested in vitro for cytokine production. These cells were stimulated with natural or recombinant Ch.a. The levels of IL-4, IL-13 and IFN-, were measured in supernatants of cultured cell 96h after stimulation using ELISA. The PBMCs of 20 normal individuals were also similarly treared for comparison of results. The production of IL-4 by the patients' cells stimulated with either Ch.a or rCh.a was significantly higher than normal levels before therapy (p=0.04 and p=0.02, respectively. After therapy, a significant decrease in production of IL-4 and a significant increase in production of IL-10 were found in PBMCs stimulated with natural Ch.a, in comparison to the results before stimulation (p=0.03 for IL-4; p=0.04 for IL-10. Similarly, these results were seen in the production of IL-4 and IL-10 stimulated with rCh.a allergen after therapy in comparison to the results before stimulation (p=0.01 for IL-4; p=0.03 for IL-10. This study suggests INC (Fluticasone propionate and oral antihistamine (Loratadine have the capacity to inhibit the production of IL-4 and shift Th2/Th1 responses, probably due to increase the level of immunoregulatory IL-10. Therefore, it could be concluded that therapy with INC and antihistamine has pharmacologic and immunologic therapeutic effects on AR patients.

  9. Prolongation of life in rats with malignant glioma by intranasal siRNA/drug codelivery to the brain with cell-penetrating peptide-modified micelles.

    Science.gov (United States)

    Kanazawa, Takanori; Morisaki, Kazuki; Suzuki, Shohei; Takashima, Yuuki

    2014-05-01

    New therapeutic strategies are required to develop candidate drugs and ensure efficient delivery of these drugs to the brain and the central nervous system (CNS). Small interfering RNA (siRNA)-based therapies have been investigated as potential novel approaches for the treatment of brain disorders. Previously, we showed that Tat, a cell-penetrating peptide derived from HIV-Tat, and the modified block copolymers (MPEG-PCL-Tat) can form stable complexes with siRNA or can be loaded with an anticancer drug and efficiently deliver the drugs to the brain tissue via intranasal delivery. In this study, to develop a novel, efficient, and safe therapeutic strategy for managing brain disorders, we used MPEG-PCL-Tat micelles with a nose-to-brain delivery system to investigate its therapeutic effects on a rat model of malignant glioma using siRNA with a Raf-1 (siRaf-1)/camptothecin (CPT) codelivery system. MPEG-PCL-Tat and CPT-loaded MPEG-PCL-Tat can form a stable complex with siRNA with a particle size from 60 to 200 nm and a positive charge at N/P ratios up to 5. Additionally, MPEG-PCL-Tat/siRaf-1 and CPT-loaded MPEG-PCL-Tat/siRaf-1 have fostered cell death in rat glioma cells after the high cellular uptake of siRaf-1/drug by the MPEG-PCL-Tat carrier. Furthermore, compared to the unloaded MPEG-PCL-Tat/siRaf-1 complex, a CPT-loaded MPEG-PCL-Tat/siRaf-1 complex achieved the high therapeutic effect because of the additive effects of CPT and siRaf-1. These results indicate that drug/siRNA codelivery using MPEG-PCL-Tat nanomicelles with nose-to-brain delivery is an excellent therapeutic approach for brain and CNS diseases.

  10. A comparison of the effect of intranasal desmopressin and intramuscular hyoscine N-butyl bromide combination with intramuscular hyoscine N-butyl bromide alone in acute renal colic

    Directory of Open Access Journals (Sweden)

    Abdol-Reza Kheirollahi

    2010-01-01

    Full Text Available Background: Patients with acute renal colic usually require immediate diagnosis and treatment. In this clinical trial analgesic effect of hyoscine N-butyl bromide and desmopressin combination in comparison with hyoscine N-butyl bromide alone in patients with acute renal colic induced by urinary stones was assessed. Methods: The study included 114 patients randomly allocated in two groups (A and B. Patients in group A received 20 mg intramuscular hyoscine N-butyl bromide at admission time and patients in group B received 20 μg of intranasal desmopressin in combination with 20 mg intramuscular hyoscine N-butyl bromide. A visual analogue scale (VAS; a 10-cm horizontal scale ranging from "zero or no pain" to "10 or unbearable pain" was hired to assess the patients′ pain severity at baseline, 30 and 60 minutes after the treatments. Results: On admission, the pain level was similar in both groups (group A: 8.95 ± 0.11 and group B: 8.95 ± 0.12. In group A, the mean of pain level showed a decrease after 30 minutes (group A: 7.26 ± 0.25 and group B: 5.95 ± 0.28 but further decreasing did not occur; however in group B, the pain consistently decreased and the mean after 60 minutes was significantly decreased (group A: 6.80 ± 0.31 and group B: 3.71 ± 0.31. No side effects were detected in this study. Conclusions: The combination of hyoscine N-butyl bromide and desmopressin is more effective than hyoscine N-butyl bromide alone in patients with renal colic. Further studies are recommended to validate these findings and compare the different doses of desmopressin.

  11. The impact of intranasal oxytocin on attention to social emotional stimuli in patients with anorexia nervosa: a double blind within-subject cross-over experiment.

    Directory of Open Access Journals (Sweden)

    Youl-Ri Kim

    Full Text Available BACKGROUND AND AIM: Social factors may be of importance causally and act as maintenance factors in patients with anorexia nervosa. Oxytocin is a neuromodulatory hormone involved in social emotional processing associated with attentional processes. This study aimed to examine the impact of oxytocin on attentional processes to social faces representing anger, disgust, and happiness in patients with anorexia nervosa. METHOD: A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with faces depicting anger, disgust, and happiness was administered to 64 female subjects: 31 patients with anorexia nervosa and 33 control students. RESULTS: Attentional bias to the disgust stimuli was observed in both groups under the placebo condition. The attentional bias to disgust was reduced under the oxytocin condition (a moderate effect in the patient group. Avoidance of angry faces was observed in the patient group under the placebo condition and vigilance was observed in the healthy comparison group; both of these information processing responses were moderated by oxytocin producing an increase in vigilance in the patients. Happy/smiling faces did not elicit an attentional response in controls or the patients under either the placebo or oxytocin conditions. CONCLUSION: Oxytocin attenuated attentional vigilance to disgust in patients with anorexia nervosa and healthy controls. On the other hand, oxytocin changed the response to angry faces from avoidance to vigilance in patients but reduced vigilance to anger in healthy controls. We conclude that patients with anorexia nervosa appear to use different strategies/circuits to emotionally process anger from their healthy counterparts.

  12. The intranasal vaccination of pregnant dams with Intimin and EspB confers protection in neonatal mice from Escherichia coli (EHEC) O157:H7 infection.

    Science.gov (United States)

    Rabinovitz, B C; Larzábal, M; Vilte, D A; Cataldi, A; Mercado, E C

    2016-05-27

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is responsible for intestinal disease and hemolytic uremic syndrome (HUS), a serious systemic complication which particularly affects children. In this study, we evaluated whether passive immunization protects from EHEC O157:H7 colonization and renal damage, by using a weaned BALB/c mouse model of infection. Recombinant proteins EspB and the carboxyl-terminal fragment of 280 amino acids of γ-intimin (γ-IntC280) were used in combination with a macrophage-activating lipopeptide-2 (MALP) adjuvant to immunize pregnant mice by the intranasal route. Neonatal mice were allowed to suckle vaccinated or sham-vaccinated dams until weaning when they were challenged by the oral route with a suspension of an E. coli O157:H7 Stx2+ strain. The excretion of the inoculated strain was followed for 72h. All vaccinated dams exhibited elevated serum IgG response against both γ-Int C280 and EspB. Passive immunization of newborn mice resulted in a significant increase in serum IgG titers against γ-Int C280 and a slight increase in EspB-specific antibodies. The neonates from vaccinated dams showed a significant reduction in EHEC O157:H7 colonization 48h post challenge. In addition, the level of plasma urea concentration, a marker of renal failure, was significantly higher in offsprings of sham-vaccinated mice. In conclusion, vaccination of pregnant dams with γ-Int C280 and EspB could reduce colonization and systemic toxicity of EHEC O157:H7 in their suckling offsprings. PMID:27129423

  13. Administrative Dimensions of Tax Reform

    OpenAIRE

    Bird, Richard M.

    2003-01-01

    The best tax policy in the world is worth little if it cannot be implemented effectively. Tax policy design in developing countries must therefore take the administrative dimension of taxation carefully into account. What can be done may to a considerable extent determine what is done in any country. This paper discusses the relationship between tax policy and tax administration. When can policy lead administration? When must policy initiatives wait on administrative reform? How exactly can b...

  14. The interpretation of administrative contracts

    Directory of Open Access Journals (Sweden)

    Cătălin-Silviu SĂRARU

    2014-06-01

    Full Text Available The article analyzes the principles of interpretation for administrative contracts, in French law and in Romanian law. In the article are highlighted derogations from the rules of contract interpretation in common law. Are examined the exceptions to the principle of good faith, the principle of common intention (willingness of the parties, the principle of good administration, the principle of extensive interpretation of the administrative contract. The article highlights the importance and role of the interpretation in administrative contracts.

  15. The impact of oxytocin administration on charitable donating is moderated by experiences of parental love-withdrawal

    Directory of Open Access Journals (Sweden)

    Marinus H. Van Ijzendoorn

    2011-10-01

    Full Text Available Oxytocin has been implicated in a variety of prosocial processes but most of this work has used laboratory tasks (such as the ultimatum game or the dictator game to evaluate oxytocin’s prosocial effects. In a double blind randomized trial we examined the influence of intranasal administration of oxytocin on real, high-cost donating money to a charity without any expectation for reciprocation. Participants in the current study were 57 female undergraduate students, aged 18-30 years, who received a nasal spray containing either 24 IU of oxytocin or a placebo, and were then given the opportunity to make a charitable donation. The participants reported how often their parents used love-withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. Oxytocin appeared to increase the participants’ willingness to donate money to a charity but only in participants who experienced low levels of parental love-withdrawal. In contrast, oxytocin administration was ineffective in enhancing donating behavior in individuals who experienced high levels of parental love-withdrawal. We conclude that the positive effect of oxytocin administration on prosocial behavior may be limited to individuals with supportive backgrounds.

  16. Administrators' Decisions about Resource Allocation

    Science.gov (United States)

    Knight, William E.; Folkins, John W.; Hakel, Milton D.; Kennell, Richard P.

    2011-01-01

    Do academic administrators make decisions about resource allocation differently depending on the discipline receiving the funding? Does an administrator's academic identity influence these decisions? This study explored those questions with a sample of 1,690 academic administrators at doctoral-research universities. Participants used fictional…

  17. Control over Administrative Contract Formation

    Directory of Open Access Journals (Sweden)

    Frane Staničić

    2016-02-01

    Full Text Available Administrative contracts in Croatian legislation represent a novelty introduced into the General Administration Procedure Act in 2010. This is a novelty which has not proved to be successful in practice. Control over administrative contract formation is inevitable and is very significant for a number of reasons. Firstly, public legal bodies which form them do so by exercising their own public powers which are without doubt subject to legality control; secondly, in forming administrative contracts, public funds are used which must be controlled; thirdly, forming administrative contracts often touches on using public goods. Due to the restrictive interpretation of administrative contracts in Croatian legislation, this institute is indisputably only regulated in the General Taxation Act. However, for more than two decades contracts which satisfy all presumptions have existed in our law in order to be considered as administrative contracts. It is for this reason that control over contracts will be dealt with for contracts considered by the author to be administrative contracts. These are contracts on concessions and contracts on public procurement. How inadequate today’s regulation of control of administrative contract formation is will be demonstrated, particularly regarding contracts on concession and public procurement. Legislative changes will be proposed which should result in a more quality system of control over administrative contract formation. How control over administrative contract formation cannot be considered as separate from control over administrative contract execution will also be shown.

  18. A review of the clinical efficacy and safety of MP-AzeFlu, a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate, in clinical studies conducted during different allergy seasons in the US

    Directory of Open Access Journals (Sweden)

    Prenner BM

    2016-07-01

    Full Text Available Bruce M Prenner Allergy Associates Medical Group, Inc., San Diego, CA, USA Abstract: A novel intranasal formulation of azelastine HCl (AZE, an antihistamine and fluticasone propionate (FP, a corticosteroid in a single spray (MP-AzeFlu [Dymista®] was studied in four randomized, double-blind, placebo-controlled trials of patients with seasonal allergic rhinitis conducted in the US. Study sites were distributed so that all major US geographic regions and the prevalent pollens within these regions were represented. Spring and summer studies included patients aged 12 years and older with allergy to grass and tree pollens. Fall studies enrolled patients with allergy to weeds, in particular ragweed. In addition, a study was conducted during the winter months in patients with allergy to mountain cedar pollen in TX, USA. Regardless of allergy season or prevalent pollen, MP-AzeFlu improved nasal symptoms of allergic rhinitis (AR to a significantly greater degree than AZE or FP, two treatments that currently are recommended as the first-line AR therapy. MP-AzeFlu improved all individual AR symptoms and was significantly better than FP and AZE for nasal congestion relief, which is generally accepted as the most bothersome symptom for AR patients. The onset of action was within 30 minutes. MP-AzeFlu also provided clinically important improvement in the overall Rhinoconjunctivitis Quality of Life Questionnaire score and significantly improved ocular symptoms of rhinitis compared to placebo. Favorable characteristics of the MP-AzeFlu formulation as well as superior clinical efficacy make it an ideal intranasal therapy for AR. Keywords: Dymista, seasonal allergic rhinitis, grass pollen, ragweed, Texas mountain cedar, intranasal therapy

  19. Key Obama officials leave administration

    Science.gov (United States)

    Showstack, Randy

    2013-01-01

    Secretary of the Interior Ken Salazar is one of the latest members of the Obama administration to announce that he is leaving his position near the start of President Obama's second term in office. Salazar, who has served as interior secretary since January 2009, intends to leave the department by the end of March, the department noted on 16 January. Salazar joins a number of other key officials who are planning to leave the administration. They include Environmental Protection Agency administrator Lisa Jackson, National Oceanic and Atmospheric Administration administrator Jane Lubchenco, and U.S. Geological Survey director Marcia McNutt.

  20. UML IN BUSINESS ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    Daniel Ionita

    2010-12-01

    Full Text Available The article elaborates weather UML, primarily used in software engineering, can be a useful tool in business modeling and administration. By analyzing the advantages the modeling language has to offer we find that UML is visual and object oriented and that it is useful in expressing structure, interaction and behavior as well. With its help managers and business people can build models and diagrams to help put things into perspective. “Case Study 1” shows UML can be used as an analysis tool in business modeling to help increase the complexity and depth of the event or project that is being developed. “Case Study 2” attempts to prove that UML can also be efficiently used in finding solutions to newly appeared problems in a business environment. Despite the practicality of the Unified Modeling Language there is still some criticism brought to it. Some programmers consider it to be hard to learn and some developers claim that it is too abstract. The article concludes that despite the minor drawbacks; due to its adaptability and complex visual models, it is a very useful tool that adds value to the modeling of business structures and processes.

  1. Gellan gum-based mucoadhesive microspheres of almotriptan for nasal administration: Formulation optimization using factorial design, characterization, and in vitro evaluation

    Directory of Open Access Journals (Sweden)

    Zaheer Abbas

    2014-01-01

    Full Text Available Background: Almotriptan malate (ALM, indicated for the treatment of migraine in adults is not a drug candidate feasible to be administered through the oral route during the attack due to its associated symptoms such as nausea and vomiting. This obviates an alternative dosage form and nasal drug delivery is a good substitute to oral and parenteral administration. Materials and Methods: Gellan gum (GG microspheres of ALM, for intranasal administration were prepared by water-in-oil emulsification cross-linking technique employing a 2 3 factorial design. Drug to polymer ratio, calcium chloride concentration and cross-linking time were selected as independent variables, while particle size and in vitro mucoadhesion of the microspheres were investigated as dependent variables. Regression analysis was performed to identify the best formulation conditions. The microspheres were evaluated for characteristics such as practical percentage yield, particle size, percentage incorporation efficiency, swellability, zeta potential, in vitro mucoadhesion, thermal analysis, X-ray diffraction study, and in vitro drug diffusion studies. Results: The shape and surface characteristics of the microspheres were determined by scanning electron microscopy, which revealed spherical nature and nearly smooth surface with drug incorporation efficiency in the range of 71.65 ± 1.09% - 91.65 ± 1.13%. In vitro mucoadhesion was observed the range of 79.45 ± 1.69% - 95.48 ± 1.27%. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of drug in the microspheres. In vitro drug diffusion was Higuchi matrix controlled and the release mechanism was found to be non-Fickian. Stability studies indicated that there were no significant deviations in the drug content, in vitro mucoadhesion and in vitro drug diffusion characteristics. Conclusion: The investigation revealed promising potential of GG microspheres for delivering ALM

  2. Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

    Directory of Open Access Journals (Sweden)

    Craig F Ferris

    2015-09-01

    Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

  3. Induction of tolerance with intranasal administration of human cartilage gp-39 in DBA/1 mice - Amelioration of clinical, histologic, and radiologic signs of type II collagen-induced arthritis

    NARCIS (Netherlands)

    Joosten, LAB; Coenen-de Roo, CJJ; Helsen, MMA; Lubberts, E; Boots, AMH; van den Berg, WB; Miltenburg, AMM

    2000-01-01

    Objective. Human cartilage glycoprotein 39 (HC gp-39) was recently identified as a candidate autoantigen in the pathogenesis of rheumatoid arthritis, In the present studies, we investigated the capacity of HC gp-39 to interfere in clinical disease induced by an unrelated autoantigen, type II collage

  4. Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses.

    Directory of Open Access Journals (Sweden)

    Muhammad Shafique

    Full Text Available INTRODUCTION: RSV infection remains a serious threat to newborns and the elderly. Currently, there is no vaccine available to prevent RSV infection. A mucosal RSV vaccine would be attractive as it could induce mucosal as well as systemic antibodies, capable of protecting both the upper and lower respiratory tract. Previously, we reported on a virosomal RSV vaccine for intramuscular injection with intrinsic adjuvant properties mediated by an incorporated lipophilic Toll-like receptor 2 (TLR2 ligand. However, it has not been investigated whether this virosomal RSV vaccine candidate would be suitable for use in mucosal immunization strategies and if additional incorporation of other innate receptor ligands, like NOD2-ligand, could further enhance the immunogenicity and protective efficacy of the vaccine. OBJECTIVE: To explore if intranasal (IN immunization with a virosomal RSV vaccine, supplemented with TLR2 and/or NOD2-ligands, is an effective strategy to induce RSV-specific immunity. METHODS: We produced RSV-virosomes carrying TLR2 (Pam3CSK4 and/or NOD2 (L18-MDP ligands. We tested the immunopotentiating properties of these virosomes in vitro, using TLR2- and/or NOD2-ligand-responsive murine and human cell lines, and in vivo by assessing induction of protective antibody and cellular responses upon IN immunization of BALB/c mice. RESULTS: Incorporation of Pam3CSK4 and/or L18-MDP potentiates the capacity of virosomes to activate (antigen-presenting cells in vitro, as demonstrated by NF-κB induction. In vivo, incorporation of Pam3CSK4 in virosomes boosted serum IgG antibody responses and mucosal antibody responses after IN immunization. While L18-MDP alone was ineffective, incorporation of L18-MDP in Pam3CSK4-carrying virosomes further boosted mucosal antibody responses. Finally, IN immunization with adjuvanted virosomes, particularly Pam3CSK4/L18-MDP-adjuvanted-virosomes, protected mice against infection with RSV, without priming for enhanced

  5. Virtual Reality and Public Administration

    OpenAIRE

    Tózsa, István

    2013-01-01

    This study serves as an introduction to how virtual reality systems could be applied in public administration and what research tasks would be necessary to accomplish a project. E-government solutions began to emerge in public administration approximately a decade ago all over the developed world. Administration service facilities via the Internet did not attract many customers, because of the digital divide. E-government solutions were extended to mobile devices as well, but the expected bre...

  6. A review of the clinical efficacy and safety of MP-AzeFlu, a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate, in clinical studies conducted during different allergy seasons in the US

    Science.gov (United States)

    Prenner, Bruce M

    2016-01-01

    A novel intranasal formulation of azelastine HCl (AZE, an antihistamine) and fluticasone propionate (FP, a corticosteroid) in a single spray (MP-AzeFlu [Dymista®]) was studied in four randomized, double-blind, placebo-controlled trials of patients with seasonal allergic rhinitis conducted in the US. Study sites were distributed so that all major US geographic regions and the prevalent pollens within these regions were represented. Spring and summer studies included patients aged 12 years and older with allergy to grass and tree pollens. Fall studies enrolled patients with allergy to weeds, in particular ragweed. In addition, a study was conducted during the winter months in patients with allergy to mountain cedar pollen in TX, USA. Regardless of allergy season or prevalent pollen, MP-AzeFlu improved nasal symptoms of allergic rhinitis (AR) to a significantly greater degree than AZE or FP, two treatments that currently are recommended as the first-line AR therapy. MP-AzeFlu improved all individual AR symptoms and was significantly better than FP and AZE for nasal congestion relief, which is generally accepted as the most bothersome symptom for AR patients. The onset of action was within 30 minutes. MP-AzeFlu also provided clinically important improvement in the overall Rhinoconjunctivitis Quality of Life Questionnaire score and significantly improved ocular symptoms of rhinitis compared to placebo. Favorable characteristics of the MP-AzeFlu formulation as well as superior clinical efficacy make it an ideal intranasal therapy for AR. PMID:27468241

  7. Comparison of topical administration of clotrimazole through surgically placed versus nonsurgically placed catheters for treatment of nasal aspergillosis in dogs: 60 cases (1990-1996)

    International Nuclear Information System (INIS)

    To examine the clinical response to topical administration of clotrimazole in dogs with nasal aspergillosis, to compare effect of surgically placed versus nonsurgically placed catheters used for administration on outcome, and to examine whether subjective scoring of computed tomographic images can predict outcome. Retrospective case series. 60 dogs with nasal aspergillosis. Information including signalment, history, diagnostics, treatment method, and outcome was retrieved from medical records of dogs with nasal aspergillosis treated between 1990 and 1996 at the University of California School of Veterinary Medicine or cooperating referral practices. Final outcome was determined by telephone conversations with owners and referring veterinarians. Images obtained before treatment were subjectively assessed to develop an algorithm for predicting outcome. Clotrimazole solution (1%) was infused during a 1-hour period via catheters surgically placed in the frontal sinus and nose (27 dogs) and via nonsurgically placed catheters in the nose (18). An additional 15 dogs received 2 to 4 infusions by either route. Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. The scoring system correctly classified dogs with unfavorable and favorable responses 71 to 78% and 79 to 93% of the time, respectively. Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications

  8. Administration Time Between Seasonal Live-Attenuated Influenza Vaccine and Trivalent Influenza Vaccine During the “Stop Flu at School” Campaign— Hawaii, 2009

    Science.gov (United States)

    He, Hua H.; Park, Sarah Y.

    2014-01-01

    Objectives We determined whether the administration time differed between seasonal intranasal live-attenuated influenza vaccine (LAIV) and seasonal injectable trivalent inactivated influenza vaccine (TIV) during Hawaii's 2009 school-located influenza vaccination clinics. This information is useful for public health response and allows further investigation into possible differences between the two vaccines. Methods We conducted a prospective cohort study in 15 public schools to determine mean times to administer LAIV and TIV to students. We performed group analyses to control for various clinic characteristics and conducted a stratified, weighted analysis. Results A total of 4,701 students were enrolled in the study, and administration time was obtained for 3,869 (82%) students (1,492 [39%] LAIV and 2,377 [61%] TIV). The mean administration time for LAIV was 62 seconds and for TIV was 90 seconds, a difference of 28 seconds (p<0.01). This finding remained significant in the stratified analysis. Conclusions Although results indicated that both LAIV and TIV can be administered rapidly among school-aged populations, LAIV was faster to administer. This finding, in addition to the greater immunogenicity of LAIV compared with TIV among children, may be an important consideration for public health administrators in planning school-located mass vaccination clinics and encouraging patient acceptance of this vaccine. PMID:24791020

  9. Coaches Guide to Sport Administration.

    Science.gov (United States)

    Leith, Larry M.

    This guide for athletic coaches offers a practical approach to the administrative functions of organizing, planning, leading, and controlling. Included are chapters on coaching administration, fund raising, organizing competitions, and designing effective budgets and controls. The guide addresses the following topics: (1) the categories of…

  10. Postmodernism in Higher Educational Administration

    Science.gov (United States)

    Demaris, Michalyn C.; Kritsonis, William Allan

    2007-01-01

    Postmodernism has many inferences that can be applied to the theory and practice of higher educational administration. Today, in higher education administrators are continuously focused on strategies that will ensure the future of minority educational institutions. As a result postmodernism is an important factor in the future of higher…

  11. Administrative Approaches to Educational Productivity.

    Science.gov (United States)

    Koski, William S.; Levin, Henry M.

    1998-01-01

    Presents an institutional framework for raising higher education productivity through administrative and organizational devices: first, by examining two theories for explaining rising higher education costs and their different policy consequences, and then by presenting an administrative process for improving productivity that focuses on…

  12. Toward an Applied Administrative Science.

    Science.gov (United States)

    Dunbar, Roger L. M.

    1983-01-01

    A study of 65 articles from the 1981 volumes of "Administrative Science Quarterly" and "Harvard Business Review," using smallest space analysis, found that the few studies adopting subjective (instead of objective) approaches to analyzing organizational change were most likely to provide a basis for an applied administrative science. (Author/RW)

  13. Emotional Intelligence in School Administrators

    Directory of Open Access Journals (Sweden)

    Emine BABAOĞLAN

    2010-04-01

    Full Text Available One of the variables that affects success in business life is emotional intelligence of working people. The purpose of this research is to identify whether the school administrators’ emotional intelligence scores differ meaningfully according to their gender, marital status, branch, being a principal or assistant principal, being elementary school administrator or high school administrator, having manegerial education course or not, educational background, period of occupational service, age, length of administration service, number of children. 180 administrators working as a principals and vise principals who worked in 2005 in Düzce elementary schools and high schools were surveyed in line with this aim. Mann-Whitney U-test, Kruskal Wallis test and ANOVA were used in order to find out groups that differ from others. It has been found that school administrators’ emotional intelligence scores differ meaningfully in terms of administrators’ branch and being elementary school administrator or high school.

  14. Administration on Intellectual and Developmental Disabilities

    Science.gov (United States)

    ... Us Home > Programs & Activities > Administration on Disabilities > AIDD Administration on Intellectual and Developmental Disabilities (AIDD) Realizing the ... AIDD has a new address and phone number: Administration for Intellectual and Developmental Disabilities, Administration for Community ...

  15. 鼻用抗组胺药物治疗变应性鼻炎的Meta分析%Efficacy of intranasal antihistamine in the treatment of allergic rhinitis: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    冯韶燕; 邓春涛; 李磊; 廖伟; 樊韵平; 许庚; 李华斌

    2014-01-01

    Objective To systematically evaluate the efficacy of intranasal antihistamine in the treatment of allergic rhinitis.Methods The randomized controlled trials (RCT) about intranasal antihistamines for the treatment of allergic rhinitis between January 1985 and January 2014 were searched in OVID,PubMed,EMBASE,CNKI,WanFang Data and Cochrane Library.Two reviewers independently screened the literatures,extracted the data,and evaluated the methodological quality,then meta-analysis was performed by using RevMan 5.1 software.Results A total of thirteen RCTs were included.The results of meta-analysis showed that the efficacy of intranasal antihistamine group was superior to the placebo group in total nasal symptom scores (TNSS),the difference was significant [WMD =-1.96,95% CI (-2.06; -1.85),P < 0.01],and individual nasal symptom scores (blocked nose,rhinorrhea,and sneezing)[WMD=-0.18,95%CI (-0.28;-0.08); WMD=-0.45,95%CI (-0.52;-0.38) ;WMD=-0.41,95% CI (-0.58 ;-0.24),all P < 0.01],with significant differences.There was no significant difference between the intranasal antihistamine group and the corticosteroid group in TNSS [WMD =-1.51,95% CI (-3.51; 0.49),P =0.14],but the intranasal antihistamines group was superior to the corticosteroid group in individual nasal symptom scores (blocked nose,rhinorrhea,and sneezing) [WMD =-0.23,95% CI (-0.40;-0.06) ; WMD =-0.35,95% CI (-0.65 ;-0.05) ; WMD =-0.25,95% CI (-0.42;-0.08),all P < 0.05],with significant differences.The intranasal antihistamine group was superior to the oral antihistamines group in TNSS [WMD =-0.88,95% CI (-1.51 ;-0.25),P < 0.01].Conclusion Intranasal antihistamine is effective in the control of nasal symptoms in AR patients.%目的 系统评价鼻用抗组胺药物治疗变应性鼻炎(AR)的临床疗效,为优化AR药物治疗提供循证参考.方法 计算机检索OVID、PubMed、EMBASE和Cochrane Librar、中国学术期刊全文数据库、万方数据库,检索时间为1985年1

  16. An Analysis of Administrative Corruption (Administrative Organizations of Yazd City)

    OpenAIRE

    Mansour Haghighatian; Somayeh Karimizadeh; Javad Nazari

    2013-01-01

    Introduction   Administrative corruption is a complicated and multi-faceted phenomenon that has many causes and ramifications, which manifest themselves in different forms in various countries and appear to be endemic of all social systems where authority is delegated. Although there might be different definitions of and approaches towards administrative corruption, the definition that has been put forward by the World Bank and Transparency International appears to be more general and compreh...

  17. Digitale kort og administrative registre

    DEFF Research Database (Denmark)

    Hansen, H. S.; Skov-Petersen, H.

    Rapporten indeholder dels en beskrivelse af de vigtigste nationale databaser med stedfæstet information og dels en vejledning i sammenstilling imellem digitale kort og administrative registre. Rapportens første del beskriver de enkelte databaser med hensyn til bl.a. adgangsforhold, indhold og...... nøgler, hvoraf sidstnævnte spiller en afgørende rolle i forbindelse med sammenstilling af digitale kort og administrative registre. Rapportens anden del fokuserer på praktiske forsøg med sammenstilling af digitale kort og administrative register. Der gives anvisninger på sammenstilling af Bygnings- og...

  18. Transcultural perspectives in nursing administration.

    Science.gov (United States)

    Andrews, M M

    1998-11-01

    Population demographics are reshaping the healthcare work force with respect to race, ethnicity, gender, national origin, sexual orientation, age, handicap, disability, and related factors as national sensitivity to various forms of diversity grows. Given the demographic trends, it is inevitable that nurse administrators will need skill in transcultural administration as they manage diversity and identify the cultural origins of conflict in the multicultural workplace. Culture influences the manner in which administrators, staff and patients perceive, identify, define and solve problems. In this article, the complex and interrelated factors that influence workplace diversity are examined. PMID:9824983

  19. Environmental recordkeeping: The administrative record

    Energy Technology Data Exchange (ETDEWEB)

    Sprouse, B.S.

    1991-08-01

    This document provides information on an environmental records management system. It includes information on environmental recordkeeping; environmental regulations with emphasis on the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA); and the administrative record including a case study of the Hanford Site's administrative record system. This paper will focus on the following objectives: (1) Identify resources that can be used as reference tools; (2) understand the reasons for developing and maintaining an administrative record; and, (3) evaluate an existing system and identify means of complying with the regulations. 15 refs., 2 figs.

  20. 右美托咪定不同给药方式对全麻气管插管应激反应的影响%Effects of dexmedetomidine administrated in different modes on the stress reaction of endotracheal intubation

    Institute of Scientific and Technical Information of China (English)

    王晓宁; 刘鹏飞; 冯艺

    2014-01-01

    Objective To observe the effects of dexmedetomidine ( DEX ) administrated in different modes on the stress reaction in patients undergoing endotracheal intubation .Methods In this prospective , randomized , double-blind study , 90 ASAⅠand Ⅱ patients undergoing selective general anesthesia were included .The patients were randomly allocated to three groups ( n =30 ): DEX intranasal group ( group N ) , DEX intravenous group ( group V ) and control group ( group C ) .DEX were given 1 μg/kg in 1 ml intranasally and at the same time 20 ml of normal saline ( NS) was infused intravenously within 10 min just before induction of anesthesia in group N; in group V, 1 ml NS was given intranasally and dexmedetomidine 1 μg/kg in 20 ml was infused intravenously in the same way;and NS were given intranasally and intravenously respectively in the same way in group C .General anesthesia induction and endotracheal intubation were taken when the infusion were finished .MAP, HR and BIS were recorded at OR(T0), 5 min and 10 min after intranasal administration (T1,T2), 1 min (T3), 3 min (T4) and 5 min (T5) after endotracheal intubation (P<0.05);blood samples were taken at T0 , T3 , T4 , T5 to detect plasma cortisol concentration and blood glucose;the occurrence of hypoxemia (SpO2 <90%), hypertension or hypotension were also recorded .Results MAP, HR, plasma cortisol concentration and blood glucose in group C were significantly higher after endotracheal intubation in group C ( P<0.05);HR was significantly lower at T 2 and MAP, HR, plasma cortisol concentration and blood glucose fluctuated slightly and were significantly lower after endotracheal intubation in both group N and group V (P <0.05).There was no discomfort and hypoxemia during intranasal and intravenous administration, and the hemodynamics were stable in all groups . Conclusion Both modes of dexmedetomidine administration can inhibit the stress reaction effectively in patients undergoing endotracheal intubation

  1. Nasal Administration of Quercetin Liposomes Improves Memory Impairment and Neurodegeneration in Animal Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Terdthai Tong-un

    2010-01-01

    Full Text Available Problem statement: At present, the development of protective strategy against Alzheimer’s Disease (AD is increasing its importance due to the high prevalence of AD, a limitation of therapeutic efficacy and its high impacts on economic and social aspects. The development of the preventive and therapeutic strategy to protect against the path physiology induced by free radicals in AD from antioxidant has gained very much concentration. Quercetin, one of the flavonoids in fruits and vegetables, has a powerful antioxidant activity both in vitro and in vivo. However, poor absorption, rapid metabolism and limited ability to cross the blood-brain-barrier are obstacles to its use for treatment of AD. Liposome’s have been used as an effective delivery system to the brain. Advantages associated with the nasal administration over oral route include higher bioavailability due to no first pass hepatic metabolism and rapid absorption leading to shorter time to onset of effect. Based on all these points, the possible effects of quercetin liposomes via nasal route on improving cognitive behavior and neurodegeneration in animal model of Alzheimer’s disease were investigated. Approach: Male Wistar rats were pretreated with quercetin liposome’s, containing 0.5 mg of quercetin in 20 μL (dose = 20 μg, via intranasal route once daily continually for 2 weeks before and 1 week after AF64A administration. Learning and memory was evaluated using the Morris water maze test at 7 days after the AF64A administration and then the rats were sacrificed for determining the density of neurons and cholinergic neurons in hippocampus using histological and immunohistochemical techniques. Results: Nasal administration of quercetin liposome’s significantly prevented changes of spatial memory of AF64A treated rats. The cognitive enhancement of quercetin liposome’s was found to be related to its ability to inhibit the degeneration of neurons and cholinergic neurons in hippocampus

  2. Medicare Administrative Contractor Performance Evaluation

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare and Medicaid Services (CMS) has compiled a summary of overall Medicare Administrative Contractor (MAC) performance information as measured...

  3. Case and Administrative Support Tools

    Data.gov (United States)

    U.S. Environmental Protection Agency — Case and Administrative Support Tools (CAST) is the secure portion of the Office of General Counsel (OGC) Dashboard business process automation tool used to help...

  4. State Lands by Administrator - County

    Data.gov (United States)

    Minnesota Department of Natural Resources — DNR land ownership and administrative interest mapped to the PLS forty level. This layer merges the DNR Control Point Generated PLS layer with IBM mainframe-based...

  5. State Lands by Administrator - Wildlife

    Data.gov (United States)

    Minnesota Department of Natural Resources — DNR land ownership and administrative interest mapped to the PLS forty level. This layer merges the DNR Control Point Generated PLS layer with IBM mainframe-based...

  6. Managerial Techniques in Educational Administration.

    Science.gov (United States)

    Lane, John J.

    1983-01-01

    Management techniques developed during the past 20 years assume the rational bureaucratic model. School administration requires contingent techniques. Quality Circle, Theory Z, and the McKenzie 7-Framework are discussed as techniques to increase school productivity. (MD)

  7. The Land Administration Domain Model

    NARCIS (Netherlands)

    Lemmen, C.; Van Oosterom, P.J.M.; Bennett, R.

    2015-01-01

    Societal drivers including poverty eradication, gender equality, indigenous recognition, adequate housing, sustainable agriculture, food security, climate change response, and good governance, influence contemporary land administration design. Equally, the opportunities provided by technological dev

  8. US Fire Administration Fire Statistics

    Data.gov (United States)

    Department of Homeland Security — The U.S. Fire Administration collects data from a variety of sources to provide information and analyses on the status and scope of the fire problem in the United...

  9. HUD Administrative Law Judges Decisions

    Data.gov (United States)

    Department of Housing and Urban Development — This site contains substantive and precedential decisions issued by the Office of Administrative Law Judges. The site does not contain subsequent rulings or...

  10. Occupational Safety and Health Administration

    Science.gov (United States)

    ... Twitter Instagram RSS Subscribe Occupational Safety and Health Administration About OSHA A to Z Index Contact Us FAQs What's New English | Spanish MENU OSHA Search For Workers File a Complaint OSHA 10-Hour Card Personal Protective ...

  11. State Lands by Administrator - Forestry

    Data.gov (United States)

    Minnesota Department of Natural Resources — DNR land ownership and administrative interest mapped to the PLS forty level. This layer merges the DNR Control Point Generated PLS layer with IBM mainframe-based...

  12. State Lands by Administrator - Fisheries

    Data.gov (United States)

    Minnesota Department of Natural Resources — DNR land ownership and administrative interest mapped to the PLS forty level. This layer merges the DNR Control Point Generated PLS layer with IBM mainframe-based...

  13. PostgreSQL administration essentials

    CERN Document Server

    Schönig, Hans-Jürgen

    2014-01-01

    If you are a database administrator who needs to get to grips with PostgreSQL quickly and efficiently, then this book is for you. This book will also be highly beneficial if you are a project leader or a developer who is interested in knowing more about database systems or bottleneck detection, as it will enable you to work more closely and cooperatively with your administrators.

  14. Administrative bias in South Africa

    Directory of Open Access Journals (Sweden)

    E S Nwauche

    2005-01-01

    Full Text Available This article reviews the interpretation of section 6(2(aii of the Promotion of Administrative Justice Act which makes an administrator “biased or reasonably suspected of bias” a ground of judicial review. In this regard, the paper reviews the determination of administrative bias in South Africa especially highlighting the concept of institutional bias. The paper notes that inspite of the formulation of the bias ground of review the test for administrative bias is the reasonable apprehension test laid down in the case of President of South Africa v South African Rugby Football Union(2 which on close examination is not the same thing. Accordingly the paper urges an alternative interpretation that is based on the reasonable suspicion test enunciated in BTR Industries South Africa (Pty Ltd v Metal and Allied Workers Union and R v Roberts. Within this context, the paper constructs a model for interpreting the bias ground of review that combines the reasonable suspicion test as interpreted in BTR Industries and R v Roberts, the possibility of the waiver of administrative bias, the curative mechanism of administrative appeal as well as some level of judicial review exemplified by the jurisprudence of article 6(1 of the European Convention of Human Rights, especially in the light of the contemplation of the South African Magistrate Court as a jurisdictional route of judicial review.

  15. Administration of punishment in school

    Directory of Open Access Journals (Sweden)

    Lalić Nataša Z.

    2003-01-01

    Full Text Available Giving consideration to punishment, one of the inevitable elements of school discipline, always reactivates the issue of punishment administration and its effects in school setting. Punishment is administered by a beforehand-determined intention, its general and final goal being the attempt to make a child change his/her behavior so as to more successfully take part in school life. The issue of how much it is justifiable to administer punishment, as a way of directing child’s behavior, is not only raised in professional discussions but occurs as a personal dilemma with parents, teachers and all those involved in child upbringing. The definition of punishment contains certain incompatible elements in attitudes, which is reflected in punishment administration within different social contexts. Based on the analysis of research results, the paper discusses all the elements the teacher should be well acquainted with, influencing the effectiveness of punishment. The effects of punishment administration depend, among other things, on the type of punishment, way in which a person experiences and perceives punishment and the way of administering it. Prior to punishment administration, as a means of directing child’s behavior factors influencing successfulness of punishment should be established consistency in punishment administration, postponement of punishment intensity of punishment, explanation for punishment administration, nature of interrelations between a child and a person punishing him/her.

  16. 48 CFR 702.170-2 - Administrator.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administrator. 702.170-2... DEFINITIONS OF WORDS AND TERMS Definitions 702.170-2 Administrator. Administrator means the Administrator or Deputy Administrator of the U.S. Agency for International Development....

  17. 7 CFR 1000.25 - Market administrator.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Market administrator. 1000.25 Section 1000.25... Rules of Practice and Procedure Governing Market Administrators § 1000.25 Market administrator. (a) Designation. The agency for the administration of the order shall be a market administrator selected by...

  18. 7 CFR 1700.26 - Deputy Administrator.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Deputy Administrator. 1700.26 Section 1700.26... AGRICULTURE GENERAL INFORMATION Agency Organization and Functions § 1700.26 Deputy Administrator. The Deputy Administrator aids and assists the Administrator. The Deputy Administrator provides overall policy direction...

  19. 45 CFR 1336.71 - Administrative costs.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Administrative costs. 1336.71 Section 1336.71... Administrative costs. Reasonable administrative costs of the RLF may be paid out of the loan fund. The grant award agreement between the Loan Administrator and ANA will set forth the allowable administrative...

  20. INFORMATION IN THE SYSTEM OF STATE ADMINISTRATION

    OpenAIRE

    Kalytych, G.; Litosh, G.

    2009-01-01

    The article analyses the approaches to the notions of "information", "state administration system", "administrative information". The article considers the importance of of information for the whole state administration system and reveals the criteria which provide the information with administrative status. Special attention is paid to making of administrative decisions on the level of the sate which are based on effective information management.

  1. 5 CFR 831.101 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Administration. 831.101 Section 831.101 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Administration and General Provisions § 831.101 Administration. (a) OPM has charge of...

  2. 7 CFR 56.3 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Administration. 56.3 Section 56.3 Agriculture... EGGS Grading of Shell Eggs General § 56.3 Administration. The Administrator shall perform, for and... administration of the provisions of the Act and the regulations in this part. The Administrator is authorized...

  3. Intranasal coadministration of Cholera toxin with amoeba lysates modulates the secretion of IgA and IgG antibodies, production of cytokines and expression of pIgR in the nasal cavity of mice in the model of Naegleria fowleri meningoencephalitis.

    Science.gov (United States)

    Carrasco-Yepez, Maricela; Campos-Rodriguez, Rafael; Lopez-Reyes, Israel; Bonilla-Lemus, Patricia; Rodriguez-Cortes, Antonio Yahve; Contis-Montes de Oca, Arturo; Jarillo-Luna, Adriana; Miliar-Garcia, Angel; Rojas-Hernandez, Saul

    2014-11-01

    The nasal mucosa is the first contact with antigens to induce IgA response. The role of this site has rarely been studied. We have shown than intranasal administration with Naegleria fowleri lysates plus Cholera toxin (CT) increased the protection (survival up to 100%) against N. fowleri infection in mice and apparently antibodies IgA and IgG together with polymorphonuclear (PMN) cells avoid the attachment of N. fowleri to apical side of the nasal epithelium. We also observed that nasal immunization resulted in the induction of antigen-specific IgG subclasses (IgG1 and IgG2a) in nasal washes at days 3 and 9 after the challenge and IgA and IgG in the nasal cavity, compared to healthy and infected mice. We found that immunization with both treatments, N. fowleri lysates plus CT or CT alone, increased the expression of the genes for alpha chain, its receptor (pIgR), and it also increased the expression of the corresponding proteins evidenced by the ∼65 and ∼74kDa bands, respectively. Since the production of pIgR, IgA and IgG antibodies, is up-regulated by some factors, we analyzed the expression of genes for IL-10, IL-6, IFN-γ, TNF-α and IL-1β by using RT-PCR of nasal passages. Immunization resulted in an increased expression of IL-10, IL-6, and IFN-γ cytokines. We also aimed to examine the possible influences of immunization and challenge on the production of inflammatory cytokines (TNF-α and IL-1β). We observed that the stimulus of immunization inhibits the production of TNF-α compared to the infected group where the infection without immunization causes an increase in it. Thus, it is possible that the coexistence of selected cytokines produced by our immunization model may provide a highly effective immunological environment for the production of IgA, IgG and pIgR as well as a strong activation of the PMN in mucosal effector tissue such as nasal passages.

  4. Capacity Building in Land Administration

    DEFF Research Database (Denmark)

    Enemark, Stig; Williamson, I

    2004-01-01

    Capacity building increasingly seen as a key component of land administration projects in developing and countries in transition undertaken by the international development banks and individual country development assistance agencies. However, the capacity building concept is often used within...... infrastructures for implementing land policies in a sustainable way. Where a project is established to create land administration infrastructures in developing or transition countries, it is critical that capacity building is a mainstream component, not as an add-on, which is often the case. In fact such projects...... should be dealt with as capacity building projects in themselves.    The article introduces a conceptual analytical framework that provides some guidance when dealing with capacity building for land administration in support of a broader land policy agenda....

  5. Meritocratic administration and democratic stability

    DEFF Research Database (Denmark)

    Cornell, Agnes; Lapuente, Victor

    2014-01-01

    This paper presents a hypothesis for understanding democratic stability based on the distinction between politicized and meritocratic bureaucracies. We argue that in a politicized administration, the professional careers of large numbers of government officials depend directly upon which party wins......, in democracies with meritocratic administrations, incumbents are credibly constrained from undertaking partial policies because their hands are tied in terms of managing the staff policy of the state apparatus. Consequently, countries with meritocratic bureaucracies have greater prospects for democratic...... stability. Empirically, we illustrate the mechanisms with two well-documented cases of democratic transitions that enshrined a politicized administration – Spain (1876–1936) and Venezuela (1958–1998) – and one transition that kept a meritocratic bureaucracy, Spain (1975–)....

  6. Policy and Public Administration, Educational Policy and Administration.

    Science.gov (United States)

    Barrientos-Monzon, Ivan Luis

    This paper attempts to clean up some of the muddled thinking that obscures the distinction between theory and practice in educational administration. The author also applies his argument to the issue of possible gaps between policy formulation and policy implementation. The author begins by noting that there is a common misapprehension that in…

  7. TWRS information locator database system administrator`s manual

    Energy Technology Data Exchange (ETDEWEB)

    Knutson, B.J., Westinghouse Hanford

    1996-09-13

    This document is a guide for use by the Tank Waste Remediation System (TWRS) Information Locator Database (ILD) System Administrator. The TWRS ILD System is an inventory of information used in the TWRS Systems Engineering process to represent the TWRS Technical Baseline. The inventory is maintained in the form of a relational database developed in Paradox 4.5.

  8. Professional SQL Server 2005 administration

    CERN Document Server

    Knight, Brian; Snyder, Wayne; Armand, Jean-Claude; LoForte, Ross; Ji, Haidong

    2007-01-01

    SQL Server 2005 is the largest leap forward for SQL Server since its inception. With this update comes new features that will challenge even the most experienced SQL Server DBAs. Written by a team of some of the best SQL Server experts in the industry, this comprehensive tutorial shows you how to navigate the vastly changed landscape of the SQL Server administration. Drawing on their own first-hand experiences to offer you best practices, unique tips and tricks, and useful workarounds, the authors help you handle even the most difficult SQL Server 2005 administration issues, including blockin

  9. Administration in an operating plant

    International Nuclear Information System (INIS)

    The importance of strict administrative procedures in the daily work is being demonstrated by commenting on events that occured in the operation of German nuclear power plants. The procedure for working in an area of the plant (pressurized medium, high-radioactive level, explosive of flammable mediums), where special measures for safe working have to be taken, is discussed in detail. The administrative problems during refuelling time are further on mentioned, especially the problems connected with administering more than 1,000 people with respect to health protection and sabotage protection. Some general comments on the influences from external causes (authorities, courts, etc.) are given. (orig./ORU)

  10. Beginning SQL Server 2008 Administration

    CERN Document Server

    Walters, R

    2009-01-01

    Beginning SQL Server 2008 Administration is essential for anyone wishing to learn about implementing and managing SQL Server 2008 database. From college students, to experienced database administrators from other platforms, to those already familiar with SQL Server and wanting to fill in some gaps of knowledge, this book will bring all readers up to speed on the enterprise platform Microsoft SQL Server 2008. * Clearly describes relational database concepts* Explains the SQL Server database engine and supporting tools* Shows various database maintenance scenarios What you'll learn* Understand c

  11. 76 FR 45621 - Employment and Training Administration

    Science.gov (United States)

    2011-07-29

    ... Employment and Training Administration Comment Request for Extension of Information Collection (Without... Temporary Employment Certification AGENCY: Employment and Training Administration. ACTION: Notice. SUMMARY... Training Administration (ETA) is soliciting comments concerning the extension of the approval for...

  12. 75 FR 6433 - Federal Aviation Administration

    Science.gov (United States)

    2010-02-09

    ... Federal Aviation Administration Notice of Availability of a Draft Environmental Assessment and Public...: Federal Aviation Administration (FAA), DOT. ACTION: Notice of Availability of a Draft Environmental... Chicago, Illinois. SUMMARY: The Federal Aviation Administration (FAA) proposes to fund, construct,...

  13. 76 FR 5212 - Employment and Training Administration

    Science.gov (United States)

    2011-01-28

    ... Employment and Training Administration Comment Request for Information Collection for Internal Fraud and...: Employment and Training Administration (ETA), Department of Labor. ACTION: Notice. SUMMARY: The Department of.... Currently, the Employment and Training Administration is soliciting comments concerning the Office...

  14. 76 FR 77302 - Federal Transit Administration

    Science.gov (United States)

    2011-12-12

    ... Federal Transit Administration FY 2011 Discretionary Sustainability Funding Opportunity; Transit... Discretionary Bus and Bus Facilities Program AGENCY: Federal Transit Administration (FTA), DOT. ACTION: FTA...'s (DOT) Federal Transit Administration (FTA) announces the selection of Fiscal Year (FY)...

  15. 76 FR 78966 - Federal Aviation Administration

    Science.gov (United States)

    2011-12-20

    ... Federal Aviation Administration Approval of Noise Compatibility Program for Kona International Airport at Keahole, Keahole, North Kona, HI AGENCY: Federal Aviation Administration, DOT. ACTION: Notice. SUMMARY: The Federal Aviation Administration (FAA) announces its findings on the noise compatibility...

  16. 75 FR 12809 - Federal Aviation Administration

    Science.gov (United States)

    2010-03-17

    ... Federal Aviation Administration Notice of Intent To Rule on Request To Release Airport Property at the Dallas/Fort Worth International Airport, DFW Airport, Texas AGENCY: Federal Aviation Administration (FAA... Aviation Administration, Southwest Region, Airports Division, Texas Airports Development Office,...

  17. 75 FR 18014 - Federal Highway Administration

    Science.gov (United States)

    2010-04-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Highway Administration AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of...: Federal Highway Administration, Kentucky Division: Mr. Greg Rawlings, Transportation Specialist, 330...

  18. 78 FR 32470 - Employment and Training Administration

    Science.gov (United States)

    2013-05-30

    ... Employment and Training Administration Investigations Regarding Eligibility To Apply for Worker Adjustment..., the Director of the Office of Trade Adjustment Assistance, Employment and Training Administration, has... Trade Adjustment Assistance, Employment and Training Administration, U.S. Department of Labor, Room...

  19. POLITICS-ADMINISTRATION DICHOTOMY: A CENTURY DEBATE

    OpenAIRE

    Reza TAHMASEBI; Seyyed Mohammad Mahdi MUSAVI

    2011-01-01

    The issue of politics-administration dichotomy as one of the five great issues in the field of public administration has had a strange history. For more than a century it has been one of the most disreputable notions in the field of public administration. At the heart of the public administration is the relationship between administrators, on one hand, and politicians and the public on the other hand. The nature of that relationship and the proper role of political leaders and administrators ...

  20. The Study on Privilege in Administrative Contract

    Institute of Scientific and Technical Information of China (English)

    于韬文

    2016-01-01

    With the continuous development of management methods, as the implementation means of administrative policy and social management ideal, the administrative contract has been widely accepted. Administrative areas contract to become the focus of people's attention. Administrative priority in administrative contract is to distinguish between private rights contract with the most critical characteristics of administrative contracts. But there are many problems of administrative priority in practice. In this paper, writer begins from the content of administrative priority and put forward myself proposals for the improvement of power supervision.

  1. Philippines - Revenue Administration Reform Project (RARP) Evaluation

    Data.gov (United States)

    Millenium Challenge Corporation — The Millennium Challenge Account-Philippines' (MCA-P) implementation of the Revenue Administration Reform Project (RARP) is expected to improve tax administration,...

  2. 78 FR 29245 - U.S. General Services Administration Federal Property Management Regulations; Administrative Wage...

    Science.gov (United States)

    2013-05-20

    ... Administration Federal Property Management Regulations; Administrative Wage Garnishment AGENCY: Office of the... amending the U.S. General Services Administration Property Management Regulation (GSPMR) to remove... telephone number. The Administrative Wage Garnishment Code of Federal Regulations (CFR) Parts affected...

  3. Novel Approaches to Surfactant Administration

    OpenAIRE

    Samir Gupta; Donn, Steven M.

    2012-01-01

    Surfactant replacement therapy has been the mainstay of treatment for preterm infants with respiratory distress syndrome for more than twenty years. For the most part, surfactant is administered intratracheally, followed by mechanical ventilation. In recent years, the growing interest in noninvasive ventilation has led to novel approaches of administration. This paper will review these techniques and the associated clinical evidence.

  4. CONTRACT ADMINISTRATIVE TRACKING SYSTEM (CATS)

    Science.gov (United States)

    The Contract Administrative Tracking System (CATS) was developed in response to an ORD NHEERL, Mid-Continent Ecology Division (MED)-recognized need for an automated tracking and retrieval system for Cost Reimbursable Level of Effort (CR/LOE) Contracts. CATS is an Oracle-based app...

  5. RARE II: The Administration's View

    Science.gov (United States)

    Cutler, M. Rupert

    1977-01-01

    RARE II is a new Roadless Area Review and Evaluation of the National Forest system. Administrators are attempting to inventory existing wilderness areas and to determine criteria for setting aside additional ones. This information will be used for the required 1980 update of the national assessment of forests and rangelands. (MA)

  6. Women Administrators as Instructional Leaders

    Science.gov (United States)

    Horner, Beth A.

    2013-01-01

    Women are under-represented in educational research and are much less likely to hold administrative positions than are men. This study, using the Liberal Feminist Theory and Structural Barrier Theory, proffers possible explanations for this phenomenon. Four women leaders were interviewed to gain insight into their instructional leadership…

  7. Instructional Technology and Administrative Decisions

    Science.gov (United States)

    Eye, Glen G.; and others

    1969-01-01

    "Concerned with the spiraling problems of technology and its impact on instruction, the American Association of School Administrators (AASA) two years ago created the Committee on Technology and Instruction. Since that time the Committee has been active in investigating a number of areas relevant to the impact of technology on the public schools. …

  8. Educational Administration and Social Justice

    Science.gov (United States)

    Bates, Richard

    2006-01-01

    After observing that texts in educational administration have largely failed to address the problem of the justice and fairness of social and educational arrangements, this article goes on to examine the necessary relationships between ethical leadership, community and the notion of social justice. Such relationships are argued to be necessarily…

  9. Innovating Traditional Nursing Administration Challenges.

    Science.gov (United States)

    Joseph, M Lindell; Fowler, Debra

    2016-03-01

    The evolving and complex practice environment calls for new mindsets among nurse leaders, academics, and nurse innovators to envision innovative ways to manage and optimize traditional tasks and processes in nursing administration. The purpose of this article is to present 3 case studies that used linear programming and simulation to innovate staffing enterprises, financial management of healthcare systems, and curricula development.

  10. Financial Management in School Administration.

    Science.gov (United States)

    Tronc, Keith, Ed.

    Because Australian school principals are being given increasing autonomy, knowledge of basic accounting principles and skill in elementary financial management are becoming more necessary. This book attempts to supply school administrators with information needed to handle new accounting duties and to lay a foundation for future fuller involvement…

  11. The Administration's Crisis Multiplied by the Crisis of the Administrated

    Directory of Open Access Journals (Sweden)

    Alina Livia NICU

    2014-11-01

    Full Text Available The starting point of this work is the idea that the concept of “crisis” should be approached with no fear. It is necessary to understand it as the signal which attracts attention upon the fact that some changes are appropriate and that some rationally thought actions ought to be taken in order to soften the social phenomena occurring within a crisis period. We may say that in the core of the crisis lies impregnated the basic substance of progress and that the moment when a crisis is declared is as well the moment of a new start. It is necessary to anticipate the crisis, in order to prepare the adequate means able to soften up the shocks created by its incipit and to bring forward the progress through its action itself. One of the most necessary and useful instruments able to smooth down the crisis' effects is the early education provided to the citizens concerning the frame of the behavior to be adopted in case of crisis. The officials and the public servants are the social actors who constitute the interface between the citizen who is going to suffer the crisis and this latter's exerted pressure. The personnel from the public administration has to assume the hardest role in reducing the most possible the crisis' effects. Some possibilities are analysed that could reduce the effects of the economical, social and political crises, among which the most important is the quality of juridical norms. The Romanian legislation concerning the public charge is studied, in respect to its capacity to motivate the public servant to perform at his up most level, during crisis periods but not only then. The idea is emphasized that panic and uncontrolled social movements in case of a crisis might lead to the multiplying of the negative effects. The personnel from the public administration comes to a direct confrontation with the pressure of the negative effect of the crisis, as it is received by the public administration - understood as a structure

  12. Administrator of the China Meteorological Administration Zheng Guoguang

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Zheng Guoguang,Secretary of CPC Leadership Group,Administrator of the China Meteorological Administration,Doctor of Physics,University of Toronto,Canada,Adjunct Professor and Doctoral tutor of Beijing University,Chairman of the National Climate Committee,Chairman of Chinese Committee of the Global Climate Observing System (CGOS),Member of the National Leading Working Group on Addressing Climate Change,Energy Saving,and Emission Reduction,Deputy Director of the Office of the National Leading Group on Addressing Climate Change,Member of UN Secretary General's High-level Panel on Global Sustainability Permanent Representative of China in WMO,Member of WMO Executive Council,and Chief Representative of China in ITCC.

  13. Chapitre 4. Administrer les loteries

    OpenAIRE

    Legay, Marie-Laure

    2016-01-01

    1. Fermes ou régies ? Le mode d’administration de ces établissements n’avait rien d’anodin. Il relevait à la fois de considérations morales et économiques. Morales car les autorités de l’époque hésitaient à se compromettre dans l’administration d’un jeu par lequel on remettait sa fortune aux coups du sort. Les États pontificaux par exemple préférèrent s’en remettre à des particuliers au début de l’établissement du loto, avant de faire régir la loterie directement pour le compte de la Curie à ...

  14. Bureaucratic Administration in Modern Society

    Directory of Open Access Journals (Sweden)

    Goga Gina Livioara

    2009-06-01

    Full Text Available In the European states, a responsible administration, from a political point of view,coordinated by law, competent and professional and neutral from a public point of view, has been thebasis for the European state for a long time and a dominant model of this type of administration isrepresented by the Weberian bureaucratic model, which emphasized the value of efficiency, consistency,continuity and predictability. Bureaucracy is indispensable in any state and very important in thedemocratic regimes. Weber asserted that the bureaucratic organisation obtained power in virtue of thedecrease of the economical and social differences. The modern state depends on a bureaucratic basis,but once established, bureaucracy is among the social structures that are most difficult to eliminate. Theemergence and development of the bureaucratic mechanisms has become a monster of the modernsociety, because the bureaucracy works in the opposite direction from democracy.

  15. IBM Sametime 852 Administration Guide

    CERN Document Server

    Davis, Gabriella; Duff, Thomas

    2011-01-01

    The IBM Lotus Sametime 8.5.2 Administration Guide uses a practical, no-nonsense approach to give you the essential information you need. Using realistic scenarios, you learn how to configure and maintain your environment to meet your needs and take advantage of the flexibility offered in Sametime 8.5.2. If you are responsible for installing and administering Sametime 8.5.2, then this book is for you. If you're completely new to Sametime administration, this book will serve as your roadmap. If you're making the jump from a prior version of Sametime, then you'll see how Sametime 8.5.2 differs an

  16. 16 CFR 1.71 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Administration. 1.71 Section 1.71 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE GENERAL PROCEDURES Administration of the Fair Credit Reporting Act § 1.71 Administration. The general administration of the...

  17. 40 CFR 142.24 - Administrator's rescission.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Administrator's rescission. 142.24... Exemptions § 142.24 Administrator's rescission. If, upon notification of a finding by the Administrator under... revised schedule, the Administrator shall rescind the application of his finding to that...

  18. 42 CFR 405.1875 - Administrator review.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Administrator review. 405.1875 Section 405.1875... Appeals § 405.1875 Administrator review. (a) Basic rule: Time limit for rendering Administrator decisions, Board decisions, and action subject to immediate review. The Administrator, at his or her...

  19. 7 CFR 868.5 - Administrator.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Administrator. 868.5 Section 868.5 Agriculture... FOR CERTAIN AGRICULTURAL COMMODITIES Regulations Administration § 868.5 Administrator. The Administrator, under the authority delegated by the Secretary, is charged with administering the programs...

  20. 7 CFR 62.100 - Administrator.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Administrator. 62.100 Section 62.100 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Definitions Administration § 62.100 Administrator. The LS Program Deputy Administrator is charged with...

  1. 7 CFR 1230.603 - Administrator, FSA.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Administrator, FSA. 1230.603 Section 1230.603... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.603 Administrator, FSA. The term Administrator, FSA, means the Administrator, of the Farm Service Agency, or any officer...

  2. 7 CFR 1220.602 - Administrator, FSA.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Administrator, FSA. 1220.602 Section 1220.602... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.602 Administrator, FSA. Administrator, FSA, means the Administrator, of the Farm Service Agency, or any officer or employee of USDA...

  3. 7 CFR 800.2 - Administrator.

    Science.gov (United States)

    2010-01-01

    ... appear at part 68 of this title (7 CFR part 68). The Administrator is authorized by the Secretary to take... 7 Agriculture 7 2010-01-01 2010-01-01 false Administrator. 800.2 Section 800.2 Agriculture... § 800.2 Administrator. The Administrator is delegated, from the Secretary, responsibility...

  4. 7 CFR 1230.602 - Administrator, AMS.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Administrator, AMS. 1230.602 Section 1230.602... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.602 Administrator, AMS. The term Administrator, AMS, means the Administrator of the Agricultural Marketing Service, or...

  5. 7 CFR 1220.601 - Administrator, AMS.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Administrator, AMS. 1220.601 Section 1220.601... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.601 Administrator, AMS. Administrator, AMS, means the Administrator of the Agricultural Marketing Service, or any officer or employee...

  6. 7 CFR 1280.602 - Administrator, AMS.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Administrator, AMS. 1280.602 Section 1280.602... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.602 Administrator, AMS. Administrator, AMS, means the Administrator of the Agricultural Marketing Service, or any officer or employee of...

  7. 7 CFR 201.3 - Administrator.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Administrator. 201.3 Section 201.3 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... REGULATIONS Administration § 201.3 Administrator. The Administrator of the Agricultural Marketing Service...

  8. 7 CFR 1280.603 - Administrator, FSA.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Administrator, FSA. 1280.603 Section 1280.603... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.603 Administrator, FSA. Administrator, FSA, means the Administrator, of the Farm Service Agency, or any officer or employee of USDA to...

  9. Chronicle 1998, Administrative law/Droit administratif

    NARCIS (Netherlands)

    Bok, A.J.

    1999-01-01

    In this contribution, two recent developments in Dutch administrative law are discussed. The codification of administrative law in a General Administrative Law Act (1994) has contributed much to this field of law, but has also caused additional legal complications for the administration. In 1997 the

  10. 24 CFR 511.71 - Administrative costs.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Administrative costs. 511.71... Administration § 511.71 Administrative costs. (a) Maximum amount. Any grantee may use not to exceed 10 percent of... years for administrative costs eligible under paragraphs (b) and (c) of this section. Eligible...

  11. 24 CFR 583.135 - Administrative costs.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Administrative costs. 583.135... Administrative costs. (a) General. Up to five percent of any grant awarded under this part may be used for the purpose of paying costs of administering the assistance. (b) Administrative costs. Administrative...

  12. 7 CFR 253.4 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Administration. 253.4 Section 253.4 Agriculture... GENERAL REGULATIONS AND POLICIES-FOOD DISTRIBUTION ADMINISTRATION OF THE FOOD DISTRIBUTION PROGRAM FOR HOUSEHOLDS ON INDIAN RESERVATIONS § 253.4 Administration. (a) Federal administration. Within the...

  13. 9 CFR 354.3 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Administration. 354.3 Section 354.3... CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Administration § 354.3 Administration... prescribed in the regulations in this part and as the Secretary may require in the administration of...

  14. 7 CFR 29.51 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Administration. 29.51 Section 29.51 Agriculture... INSPECTION Regulations Administration § 29.51 Administration. The Director is charged with the supervision of the Division and the performance of all duties assigned thereto in the administration of the...

  15. 14 CFR 1201.103 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Administration. 1201.103 Section 1201.103 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1201.103 Administration. (a) NASA is headed by an Administrator, who is...

  16. 7 CFR 30.61 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Administration. 30.61 Section 30.61 Agriculture... AND STANDARDS Administration § 30.61 Administration. The Director, Tobacco Division, Agricultural... the Division and the performance of all duties assigned thereto in the administration of the...

  17. 9 CFR 381.3 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Administration. 381.3 Section 381.3... CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Administration; Application of Inspection and Other Requirements § 381.3 Administration. (a) (b) The Administrator may in specific classes of cases waive...

  18. 7 CFR 29.9231 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Administration. 29.9231 Section 29.9231 Agriculture... Tobacco Produced and Marketed in a Quota Area Administration § 29.9231 Administration. The Director... the administration of the act. The conduct of all services and the licensing or employment...

  19. 7 CFR 23.2 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Administration. 23.2 Section 23.2 Agriculture Office... Administration. (a) Title V will be administered by the Administrators of the Extension Service and the... Act of 1914 and the Hatch Act (as amended), August 11, 1955, the administration of the programs...

  20. 28 CFR 36.204 - Administrative methods.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Administrative methods. 36.204 Section 36... PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES General Requirements § 36.204 Administrative methods... standards or criteria or methods of administration that have the effect of discriminating on the basis...